Introduction Aim of Work [602811]

Introduction & Aim of Work
1 Introduction
Non-Hodgkins lymphoma is a heterogeneous group of
lymphocyte neoplasm and the primary types of Non- Hodgkins
lymphoma are classified according to the lymphocyte that is
affected: B- cell lymphoma, which is most common, and T- cell
lymphoma (Zelenetz, et al., 2008) .
There are many subtypes, each with a different prognosis. The
loosely divided classifications, as recognized by the international
lymphoma study group (ILSG), are: -Indolent (slow- growing, low
grade) , Aggressive ( high grade) And Highly aggressive lymphomas
and lymphoid leukemia (Smith., et al ., 2006).
The elucidation of etiologic factors and their mechanistic role
in the pathogenesis of this malignancy are critical to advancements
in disease prevention and treatment (Guisi et al., 2004). Current
evidence suggests that factors/conditions that precipitate either
chronic antigenic stimulation or immunosuppression may provide a
preferential milieu for development of NHL. High rates of
lymphoma have been observed among individuals with autoimmune
disease, organ transplants, and primary or acquired
immunodeficiencies (Zhao., et al ., 2004) .

Introduction & Aim of Work
2 The incidence of non- Hodgkins lymphoma (NHL) has
doubled over the past two decades in the US and most other
westernized countries (Clark and Glaser 2002). Changes in
lymphoma classification, and increases in AIDS-associated
lymphomas have contributed to the startling escalation of disease
incidence, these factors are estimated to account for only about 50%
of the increase in observed incidence (Mariette., 2001).
In Egypt, NHL is the fifth most common cancer in both the
sexes (Mokhtar., et al ., 2004). However, no epidemiological studied
were conducted in Sharkia Governorate before, so our study tried to
fill this gap.

Introduction & Aim of Work
3
Aim Of The Study
The purpose of this study is to evaluate the clinical and
epidiomlogical characteristics of non-hodgkins lymphoma patients
in Sharkia Governorate, Egypt during the period of study.

Review of Literature
4 Non-Hodgkin Lymphomas
Definition
Non-Hodgkin lymphomas (NHL) are a heterogeneous group of
lymphoproliferative disorders originating in B-lymphocytes, T-
lymphocytes or natural killer (NK) lymphocytes. Non-Hodgkin ’s
lymphoma (NHL) includes multiple neoplastic disorders of the
lymphoid system with overlapping features. NHL is characterized by
a monoclonal expansion of lymphoid cells, excluding those from
primitive precursors that give rise to acute lymphoblastic leukemia
and plasma cells that give rise to multiple myeloma.
Epidemiology
• Incidence
Non-Hodgkin Lymphoma (NHL) occurs worldwide although
there is notable geographical variation in incidence and subtype
distribution. These differences are due to a combination of
demographic, environmental and other unidentified factors. A
dramatic increase in NHL incidence was seen starting around 1970,
with subsequent stabilization 10 years ago. Despite this plateau, the
number of new cases in many countries will increase significantly in
coming years due primarily to aging populations (Skrabek et al.,
2013).
In a recent study, it was shown 115,643 NHL cases diagnosed
in the united states. NHL rates in the total population increased 0.3%
per year during 1992-2009 (Shiels et al., 2013).

Review of Literature
5 The incidence of NHL by subtype is shown in Fig. (1) (Jemal
et al., 2008).

Fig. (1) Incidence of non-hodgkin's lymphoma by subtype (Jemal et al., 2008).
• Trends and predictions
The unexplained increase in new cases was seen worldwide
regardless of regional demographics or level of economic
development (Ferlay et al., 2010).
In the United States (US) annual percent change (APC) of
ASIR was 3.6% from 1975 to 1991 (Howlader et al., 2009).
Mortality from NHL likewise increased during this period
(Howlader et al., 2009).
Canada saw similar trends, with a plateau over the last decade
in women and an ongoing small increase in men (Canadian Cancer
Society, 2012).
In NA, trends in young men mirror the HIV epidemic most
closely (Cancer Care Ontario, 2006).
In Uganda, the APC of NHL has been 6.7% in men and 11%
in women (Ulrickson et al., 2012).

Review of Literature
6 A systematic review found incidence trends to be more
pronounced in older (especially >75), white men and residents of
rural areas (Muller et al., 2005).
The NHL subtype with the greatest increase was DLBCL
(Muller et al., 2005).
Despite an overall plateau, division by subtype reveals
increasing incidence of BL in men aged 20 –64 (Howlader et al.,
2009).
Marginal zone lymphoma (MZL) and angioimmunoblastic T-
cell lymphoma has become more common in both sexes and mantle
cell lymphoma (MCL) is currently increasing by 3.3% per year in
US men over 65 years (Howlader et al., 2009).
Some of these changes can be attributed to improvements in
subtype recognition. A decline in CLL and lymphoplasmacytic
lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) is
unexplained, especially in light of proportionately more
asymptomatic, indolent cases of NHL (Roman and Smith, 2011).
Even if the ASIR remains stable by 2020 there will be a
substantial increase in new cases of NHL globally based on
predicted population changes (Ferlay et al., 2008).
The European Union and NA will see a 15.6% and 28%
increase, respectively, due primarily to their aging populations
(Ferlay et al., 2008).

Review of Literature
7 In contrast, forecasted changes in Africa (35% increase from
2008 to 2020) are due to more cases in individuals less than 65
(Ferlay et al., 2008).
• Race/ethnicity
Lymphoma is most common in whites (Morton et al., 2006).
As racial data is not included in Canadian registries little has
been reported in this area. Surveillance Epidemiology and End
Results (SEER) data from the US demonstrates notable differences
between racial groups (Howlader et al., 2009).
Blacks have a younger age at diagnosis overall, and a higher
incidence of peripheral T-cell lymphoma (Muller et al., 2005).
In the US, the relative risk (RR) of HIV-associated NHL in
blacks is half that of whites (RR 22.3, 95% CI, 17.1 –29 vs. RR 46.2,
95% CI, 38.8 –55) possibly because of ethnic variations in immune
systemregulatory genes (Koshiol et al., 2011).
An increase in incidence over time continues in American
Indians/Alaskan Natives although relatively small numbers limits
these statistics (Howlader et al., 2009).
NHL patterns of migrants have generally followed that of their
ancestral population. However, a Canadian group showed increasing
FL and a decrease in nasal T/NK cell lymphoma in Chinese migrants
(Au et al., 2005).
This implies that not all of the geographical and racial
variation is genetic, environmental factors also play a role.

Review of Literature
8 • Gender
Men have a higher rate of mortality from NHL (Canadian
Cancer Society, 2012).
Also, for unexplained reasons there is a male predominance in
almost all subtypes. This varies from 1.5:1 overall to 3:1 for BL,
MCL, hairy cell leukemia (HCl) and WM. FL and MZL rates are
similar in both sexes (Morton et al., 2006).
PMBL is an exception in that this entity predominates in
females (Swerdlow et al., 2008).
Autoimmune conditions, which are more prevalent in women,
have been consistently shown to be predisposing factors for NHL.
However, a case control study demonstrated that this association is
stronger in men (Ansell et al., 2010).
As with other risk factors, given the signi ficant heterogeneity
of NHL, further data will require strati fication by disease subtypes
(Roman and Smith, 2011).
• Risk factors
o Pathogens
§ RNA viruses: HTLV-1, hepatitic C and HIV (Adami., et al ., 2003) .
§ DNA viruses: EBV was also linked to NHL (Adami., et al ., 2003) .
§ H. pylori infection: Helicobacter pylori (H. pylori) infection
might initiate and contribute to the progression
of lymphoma from gastric mucosa-associated lymphoid tissue
(MALT) (Wang et al., 2013).

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9 o Immunodeficiency: Long-term immunosuppression as in organ
transplant recipients, congenital immunodeficiency (e.g.
agamaglobulinemia) (Alexander et al., 2007) , and autoimmune
diseases including rheumatoid arthritis, systemic lupus
erythematous, Sj ögren syndrome, ulcerative colitis and Crohn's
disease (Yu et al., 2011).
o Toxins: Polychlorinated biphenyls have been hypothesized to
increase the risk of non-Hodgkin lymphoma (NHL), although
conclusive evidence is still lacking (Maifredi et al., 2011).
o Cytogenetic abnormalities
NHL is characterized by cytogenetic abnormalities that
result in malignant expansion of B or T cells (Kuppers, 2005).
These include activation of oncogenes by chromosomal
translocation, as well as the inactivation of tumor suppressor
genes by chromosomal deletion or mutation. In some types of
NHL, exogenous genes are inserted by oncogenic viruses
(Roix et al., 2003) (Fig.2).
It is the stage of T- or B-cell development at which the
mutations occur that determines the specific malignant phenotype .
The mechanism and type of genetic alteration associated with
lymphoma is characterized by distinguishable features from other
solid tumors. During different stages of NHL, the genome of the
malignant cells is relatively stable compared with many solid
tumors, characterized by balanced chromosomal translocation and
unbalanced (reciprocal) chromosomal alterations (Johansson et al.,
1995).

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10

Fig. (2) Cellular origins of representative non-Hodgkin lymphomas (A) B cell; (B) T
cell. ALCL=anaplastic large-cell lymphoma; BCL=B-cell lymphoma;
DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma;
MCL=mantle-cell lymphoma (pre-germinal centre); MZL=marginal zone
(MALT) lymphoma (post-germinal centre); SLL=small lymphocytic
lymphoma; TCL=T-cell lymphoma (Evans and Hancock, 2003).

Chromosomal translocation is considered the genetic hallmark
of lymphoid malignancies; however, the precise mechanisms are
unknown. Most translocations involve chromosomal breakpoints
within the immunoglobulin (Ig) loci and T-cell receptor (TCR) loci
in B-cell and T-cell lesions, respectively (Tycko and Sklar,1990).
Balanced translocations are believed to be the initiating events,
followed by unbalanced chromosomal alterations in which the
exchange of chromosomal material is unequal resulting in extra or
missing genes, which are associated with disease progression. The
most common balanced translocation occurs in chromosome 14, and

Review of Literature
11 this is frequently associated with additional translocations (Morris et
al., 1994) . For example, in follicular lymphoma (FL), there are 4 to 8
chromosomal abnormalities in addition to the characteristic t (14;
18) (Horsman et al., 2001).
Mutation or deletion of p53, the most common genetic
alteration in cancer, is found in specific subsets of NHL including
late stage FL, chronic lymphocytic leukemia (CLL), small
lymphocytic lymphoma (SLL), mantle cell lymphoma, and Burkitt's
lymphoma (Sander et al., 1993).
Variants of NHL are characterized by the deletion of unknown
tumor suppressor genes, most frequently in the long arm of 6q and
deletion of chromosome 13q14 (SLL and B-cell CLL) (Kalachikov
et al., 1997).
Clinical Presentation
At least two thirds of NHL cases present with non-tender
lymph node enlargement persisting for more than 2 weeks (Golman
and Bennett, 2000). Systemic signs and symptoms include fever of
unknown origin, unexplained weight loss (> 10 %over 6 months),
drenching night sweats, visceral pain and malaise; collectively these
are known as “B symptoms ” and are identified in 40% of new cases.
These findings are more consistently seen with more aggressive
disease and are associated with a worse prognosis. Mediastinal
lymphadenopathy, seen in 20% of patients, may present with
persistent cough, chest discomfort, or pleural effusion, or may be
asymptomatic and detected only by imaging studies (Anderson et
al., 1982).

Review of Literature
12 While abdominal and pelvic lymphadenopathy is common,
symptoms, including anorexia, nausea, vomiting, pain, and weight
loss do not typically develop until there is massive enlargement or
frank obstruction . Diffuse hepatosplenomegaly is common in
indolent disease with discrete hepatic masses being more common in
aggressive and highly aggressive NHL (Risdall et al., 1979).
Primary extranodal site involvement is seen in 10% to 35% of
cases at initial diagnosis and upwards of 50% during the course of
the disease. These sites include the gastrointestinal (GI) tract, skin,
testes (in men), kidneys, and bone (Seymour et al., 2001) (Fig.3).
Systemic NHL is capable of manifesting within the CNS during
periods of progression or relapse. When NHL breaches the CNS it
can present with numerous neurological deficits, some of which may
be detected during ophthalmic examination (Anthony, 2010).
Cheng et al., (2010) reported the first coexistence of both
osseous and hepatic lymphoma in the same patient without any
lymph node involvement.
Lymphoma of the small intestine has been reported to have a
poor prognosis. The synchronous occurrence of lesions in the small
intestine or colon is unusual, and impacts the prognosis adversely
(Dughayli et al., 2011).
Emergency presentations of NHL include hypercalcemia,
superior or inferior vena cava obstruction, hyperviscosity syndrome,
severe hepatic dysfunction, and venous thromboembolic disease
(Mohren et al., 2005). Blood tests variably demonstrate anemia
(42%), thrombocytopenia (13%), leucopenia, (6 %) and elevated

Review of Literature
13 creatinine (26%-56%), these laboratory abnormalities may be of
prognostic importance as well (Hasenclever and Diehl, 1998).

Fig. (3) Cutaneous T-cell lymphoma (CTCL) with (A) involvement of the hard palate
and (B) left forearm (Mawardi et al., 2009).
Diagnosis
The majority of patients diagnosed with NHL are referred to a
hematologist/oncologist after initially presenting to their primary
care physician for further evaluation, diagnosis, and staging.
Diagnosis of NHL includes a combination of physical examination,
blood tests, imaging studies, and selective biopsies. Malignant cells
are present in the peripheral blood at diagnosis in up to 20% of
cases, generally indicating extensive bone marrow involvement and
more aggressive disease (Ankina et al., 2007).

Review of Literature
14 A diagnostic spinal tap directly combined with a first
prophylactic instillation of cytarabine and/or methotrexate is
indicated in high-risk patients according to international prognostic
index (IPI), especially with involvement of CNS, orbital, bone
marrow, testis, spine, or base of the skull. It is also indicated in the
case of HIV-associated lymphoma and highly aggressive NHL (Tilly
et al., 2008).
Diagnostic imaging studies (Fig.4,5) include chest radiograph
and computerized tomography (CT) of the abdomen and pelvis.
Chest radiograph may demonstrate alveolar opacities and
mediastinal and intrathoracic lymph node involvement (Castellino et
al., 1996). Abdominal and pelvic CT may show multiple discrete
masses or diffuse infiltration of the liver, kidneys, or GI tract
(Charnsangavej, 1990).

Fig. (4) Chest radiograph showing mediastinal lymph-node mass caused by non-
Hodgkin lymphoma (Hennessy et al., 2004).

Review of Literature
15 Positron emission tomography (PET), often combined with CT
PET/CT, is highly sensitive and specific for more aggressive NHL
although its utility in detecting indolent disease is unclear (Karam et
al., 2006). Lymph node and tissue biopsy (Fig.5) is the gold standard
diagnostic measure for NHL. Indications for lymph node biopsy
include significant enlargement, persistence for more than 4 to 6
weeks, or progressive increase in size (Pangalis et al., 1993).

Fig. (5) A, Axial noncontrast CT image at the level of the maxillary sinuses
demonstrates an expansile, destructive soft tissue mass involving the right
maxillary sinus. B, Axial 18F-FDG-PET at the same anatomic level as
image A demonstrates intense FDG uptake in the destructive soft tissue
mass with a maximal standardized uptake value (SUVmax) of 15.9. C,
Fused CT and PET image further correlates intense, abnormally increased
tracer uptake in the soft tissue mass. D, E, F, Axial CT, PET, and fused
PET-CT images through the maxillary sinus after completion of 2 cycles
of cytotoxic chemotherapy show marked decrease in size and tracer uptake
in the mass, consistent with a favorable response to chemotherapy
(Mawardi et al., 2009).

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16

Fig. (6) Histopathology of NHL (cutaneous T-cell lymphoma). A, Histopathology
(hematoxylin and eosin, magnification × 400) of the palatal lesion from Fig.
1 demonstrates a diffuse round blue cell infiltrate with prominent mitotic
figures. B, Immunohistochemistry demonstrates CD2 positivity which
confirms T-cell lineage of the neoplastic lymphocytes (Mawardi et al.,
2009).

Fine needle aspiration (FNA) is a less invasive test, but
positive findings in most cases must be confirmed by tissue biopsy
(Florentine et al., 2006). In the absence of peripheral disease, CT-
guided core needle biopsy or multiple biopsies at the time of
laparoscopy is required (Asoglu et al., 2005).
Bone marrow involvement occurs in 30% to 50% of NHL
cases, and is considered an indication of more advanced stages of

Review of Literature
17 indolent disease given its extranodal site involvement (Conlan et al.,
1990). Very infrequently NHL presents initially with marrow
involvement as pancytopenia and systemic symptoms without
evidence of peripheral disease (Ponzoni and Li, 1994). Bone
marrow disease is usually focal and involves only 30% of marrow
cellularity, therefore obtaining bilateral or multiple biopsies is often
considered (Conlan et al., 1990)
Different NHL categories can be diagnosed based on both
morphology and immunophenotyping. Immunophenotyping by flow
cytometry (FCM) plays an adjunctive role with bone marrow biopsy
and is of particular utility when considering targeted therapies to
specific phenotypes (Kaleem, 2006). FCM is especially useful in
determining B- or T-cell clonality (Kaleem et al., 2004).
Clonality is analyzed by evaluating the expression of certain
immunoglobulin and surface antigens in lymphocytes and can be
confirmed by molecular characterization of immunoglobulin or T-
cell receptor gene rearrangement. Prognosis and outcome have been
related to the expression levels of specific molecules; for example
higher expression of CD38 in CLL is associated with decreased
survival (Kaleem et al., 2006).
Classification
While a number of competing approaches have been
introduced since 1942 when Gall and Mallory proposed the first
widely used classification of NHL, the World Health Organization
(WHO) classification system for neoplastic diseases of the
hematopoietic and lymphoid tissues, introduced in 1997, is the most

Review of Literature
18 widely used today for clinical and research purposes (Table -1)
(Harris et al., 1999).
The WHO system classifies NHL as indolent, aggressive, and
highly aggressive . Indolent lymphoma accounts for 40% of all NHL
with the most common type being FL, characterized by expansion of
the lymphoid follicles within the lymph node due to the proliferation
of small malignant lymphoid cells. Chromosomal translocation of
t(14; 18) is a hallmark of FL, resulting in rearrangement of the Bcl-2
gene and overexpression of the anti-apoptotic Bcl-2 protein driven
by the immunoglobulin promoter (Young and Iland, 2007).
Less common translocations involve Bcl-2 and the
immunoglobulin light chain genes, located on chromosomes ٢ and
22. Aggressive lymphoma accounts for approximately 50% of cases
and includes diffuse large B-cell lymphoma (DLBCL). T-cell natural
killer (NK) cell lymphomas are rare but are included in this subtype
(Young et al., 2006).
Highly aggressive lymphoma, which includes Burkitt
lymphoma and lymphoblastic lymphoma, is seen more often in
younger patients and is characterized by acute onset, high
proliferative rate, and tendency toward leukemic transformation
(Kasamon and Swinnen, 2004).
Staging And Prognosis
Staging of NHL is important for both guiding therapy and
determining prognosis. The Ann Arbor staging system (Table-2)
(Lister et al., 1989) is the most widely used and takes into account

Review of Literature
19 the number of tumor sites (nodal and extranodal), location and the
presence/absence of B symptoms (Moormeier et al., 1990).
Tumor burden can be estimated by using the Group d'Etude
Lymphomes Folliculaire (GELF) method. In this method, any of the
following factors qualifies for high tumor burden: (1) systemic
symptoms; (2) 3 or more lymph nodes sites 3 cm or larger in
diameter; (3) a single lymph node site 7 cm or larger in diameter; (4)
platelets 100,000/mL or less or absolute neutrophils 1000/mL or
less; (5) circulating lymphoma cells 5000/mL or more; and (6)
marked splenomegaly, compressive symptoms, pleural effusion, or
ascites (Brice et al., 1997).

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20 Table (1) WHO classification of non-Hodgkin lymphoma (Harris et al., 1997).

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21 Small lymphocytic lymphoma
Some patients may present solely with lymphadenopathy,
organomegaly, and presence of infiltrating monoclonal B cells with
the same immunophenotype as chronic lymphocytic leukemia (CLL)
cells, but lacking peripheral blood lymphocytosis. This disease is
called small lymphocytic lymphoma (SLL) and has been considered
for almost 2 decades to be the tissue equivalent of CLL. Both CLL
and SLL are currently considered different manifestations of the
same entity by the fourth edition of the World Health Organization
Classification of Tumours of Haematopoietic and Lymphoid Tissues
(Santos and O'Brien, 2012).
Lymphoplasmacytic lymphoma
Lymphoplasmacytic lymphoma (LPL) is a low-grade, B-cell
neoplasm composed of small lymphocytes, plasmacytoid
lymphocytes, and plasma cells that typically involve the bone
marrow, and it is associated with an immunoglobulin M (IgM)
gammopathy (Naderi and Yang, 2013).
Plasma cell myeloma
Plasma cell myeloma is a B-cell neoplasm characterized by
clonal expansion of plasma cells in the bone marrow, which
produces lytic bone lesions and monoclonal protein. It is one of the
most common hematological malignancies in the United States.
Plasma cell myeloma is a rather heterogeneous disease with variable
clinical presentation and outcome determined largely by the tumor
biology as well as the host response (Ferreira, 2013).

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22 Hairy cell leukemia
Hairy cell leukemia is a rare chronic lymphoproliferative
disorder. Its diagnosis remains difficult due to different variant
forms and differential diagnosis that are splenic marginal zone
lymphoma and b-prolymphocytic leukemia (Balsat and Cornillon,
2013).
Follicular lymphoma
Follicular lymphoma (FL) is generally an indolent B-cell
lymphoproliferative disorder of transformed follicular center B cells.
FL is characterized by diffuse lymphoadenopathy, involvement of
bone marrow, splenomegaly, and less commonly other extranodal
sites of involvement. In general, cytopenias can occur but
constitutional symptoms of fever, night sweats, and weight loss are
uncommon (Freedman, 2012).
Marginal zone lymphomas
Marginal zone lymphomas (MZLs) are indolent B-cell
lymphomas that can occur outside lymph nodes (eg, gastrointestinal
tract, thyroid, orbit, leptomeninges, spinal cord, skin). Mucosa-
associated lymphoid tissue (MALT) lymphoma (MALT lymphoma,
MALToma) is the term traditionally coined for extranodal marginal
zone lymphoma of MALT (Reid and Friedberg, 2013).
Mantle cell lymphoma
Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma
characterized by involvement of the lymph nodes, spleen, blood, and
bone marrow. Diagnosis is based on lymph node, bone marrow, or

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23 tissue morphology of centrocytic lymphocytes, small cell type, or
blastoid variant cells (Vose, 2013).
T-cell large granular lymphocyte leukemia
T-cell large granular lymphocyte leukemia (T-LGL) also
known as T-cell chronic lymphocytic leukemia is rare and comprises
a small minority of all small lymphocytic leukemias (Malani et al.,
2007).
Mycosis fungoides
Mycosis fungoides is the most common type of primary
cutaneous lymphomas. The phenotype of the tumor cell corresponds
to an effector/memory-type of helper T cell which, given its
repertoire of homing receptors, is specialized for recirculation
through the skin (Beyer et al., 2011).
T-cell prolymphocytic leukemia
T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive
post-thymic malignancy with poor response to conventional
treatment and short survival. It can readily be distinguished from
other T-cell leukemias on the basis of the distinctive morphology,
immunophenotype, and cytogenetics (Dearden, 2006).
Burkitt lymphoma
Burkitt lymphoma (BL) is the most common non-Hodgkin
lymphoma in children and adolescents, but at least 30% of cases
occur in patients older than 60 years, and the absolute number of BL
cases in adults exceeds those in childhood. BL is described as a

Review of Literature
24 monomorphic proliferation of medium-sized transformed B cells
with round nuclei, clumped chromatin, basophilic cytoplasm, and
squared-off cell borders, cytoplasmic vacuoles, medium-sized
paracentral nucleoli, and a starry sky pattern (Said et al., 2014).
Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common
lymphoid malignancy in adults accounting for 31% of all NHL in
Western Countries. Following, morphological, biological and
clinical studies have allowed the subdivision of DLBCLs into
morphological variants, molecular and immunophenotypic
subgroups and distinct disease entities (Martelli et al., 2013).

Table (2) Ann Arbor Staging System

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25 Prognosis depends on the specific histopathologic variant,
immunophenotype, staging, and response to therapy. Indicators
include general, disease-specific, and treatment-specific prognostic
scores. The most commonly used general prognostic index is the
International Prognostic Index (IPI) (Table 3) (Anonymous, 1993).
Serum concentration of lactate dehydrogenase (LDH) is an
important predictor of survival in NHL as a high level of this
enzyme indicates high tissue damage and lymphoma relapse or
renewed growth (Dumontet et al., 1999).
Table (3) International Prognostic Index (IPI)

One point is assigned for each of the following risk factors:
• Age greater than 60 years
• Stage III or IV disease
• Elevated serum LDH
• ECOG/Zubrod performance status of 2, 3, or 4
• More than 1 extranodal site
The sum of the points allotted correlates with the following risk groups:
• Low risk (0-1 points) – 5-year survival of 73%
• Low-intermediate risk (2 points) – 5-year survival of 51%
• High-intermediate risk (3 points) – 5-year survival of 43%
• High risk (4-5 points) – 5-year survival of 26%

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26 Management Of NHL

I. Medical Management
Management of NHL depends in large part on the
classification (indolent, aggressive, highly aggressive) and specific
diagnosis and/or subtype. Treatment response is assessed using the
International Harmonization Project (IHP) criteria that are based
primarily on CT, PET scan, bone marrow biopsy, and clinical and
biochemical information (Table-4) (Cheson et al., 2007).
Table-4 Proposed response criteria for assessment of NHL by the International
Harmonization project (IHP) (Cheson et al., 2007).

Indolent NHL
Although the median survival of indolent NHL is longer than
10 years, it is generally considered an incurable condition, except in
rare presentations of early (Stage I) disease, or when allogeneic stem
cell transplantation is used (Harris et al., 1994). In the majority of
cases the primary goal is alleviation of complications related to

Review of Literature
27 compromised organ function, anemia, and localized symptoms
secondary to bulky disease (Liu et al., 2006).
As many patients are asymptomatic at the time of diagnosis
and studies have demonstrated no difference in survival between
patients receiving immediate treatment or observation alone, the
initial approach is often close observation without treatment. This
importantly reduces the risk of tumor cells developing resistance to
chemotherapy agents (Ardeshna et al., 2003).
Management modalities include radiotherapy alone for
localized disease or chemotherapy for more widely systemic disease
(Wilder et al., 2001). Radioimmunotherapy is also used.
Management of advanced and relapsed disease involves either
observation or chemotherapy. Chemotherapeutic strategies include
both single agents (e.g., chlorambucil, cyclophosphamide,
cladribine, fludarbine, and pentostatin) and combination therapy
(e.g., cyclophosphamide, vincristine, and prednisone [CVP] and
fludarbine with mitoxantrone and dexamethasone regiment)
(Peterson et al., 2003).
The anti-CD20 monoclonal antibody rituximab has been used
alone or in combination (e.g., R-CVP, cyclophoshamide-
doxorubicin-vincristine-prednisolone [R-CHOP]) and has
demonstrated considerable efficacy in multiple clinical studies
(Heinzerling et al., 2000).
Maintenance therapy with rituximab provides improved
outcomes in relapsed and refractory cases (van Oers et al., 2006).
Another option includes radioimmunoconjugate therapy (e.g.,

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28 ibritumomab, tositumomab), which delivers targeted radiotherapy to
tumor cells (Cheson, 2003).
• Mantle cell lymphoma
No standard approach for first-line or relapsed disease
treatment is established, nor does a curative therapy exist for most
patients. Younger patients often receive dose-intensive
chemoimmunotherapy regimens and, in many cases, consolidative
ASCT. Patients who are elderly, or those with significant comorbid
illness, are usually managed with lower-intensity chemotherapy with
or without rituximab. While most patients respond to initial therapy,
including many who achieve complete remission, the durations of
response outside the most intensive regimens and ASCT are usually
in the range of 12 – 24 months. As such, treatment for multiply-
relapsing disease is required for virtually all patients (Smith, 2008).
• Bortezomib
Bortezomib is a novel proteasome inhibitor initially approved
for use in multiple myeloma and currently under continued
investigation as a treatment for numerous subtypes of non-Hodgkin's
lymphoma. One postulated mechanism of action in non-Hodgkin's
lymphoma is the ability of bortezomib to ameliorate molecular
dysregulation in NF- κB activation and regain cell cycle control.
Results of clinical trials have varied widely based on lymphoma
subtype. While response to bortezomib has been dismal in chronic
lymphocytic leukemia and small lymphocytic lymphoma, reasonable
responses have been attained in mantle cell lymphoma leading to its

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29 US FDA approval as a second-line agent for the treatment of mantle
cell lymphoma (Koprivnikar and Cheson, 2012).
• Bendamustine
Bendamustine (bendamustine hydrochloride) is an alkylating
agent indicated in several countries for the treatment of indolent
non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma (MCL).
While the precise mechanism of action of bendamustine is as yet
unknown, it has limited cross resistance to other alkylating agents
and appears to exert its antineoplastic effects via a different
mechanism to that of other alkylating agents. Bendamustine
monotherapy was effective in treatment-refractory (including
rituximab-refractory) indolent NHL or MCL (Garnock-Jones,
2010).
• Temsirolimus
Temsirolimus (Torisel) is a mammalian target of rapamycin
(mTOR) inhibitor approved for the treatment of relapsed/refractory
mantle cell lymphoma (MCL). The recommended dosage in this
indication (175 mg once weekly for 3 weeks and then 75 mg once
weekly as maintenance) is higher than that for renal cell carcinoma;
thus, the safety profile is quite different in the two indications
(Bouabdallah et al., 2013).
• Thalidomide and lenalidomide
Thalidomide and lenalidomide are immunomodulatory drugs
that show promise in mantle cell lymphoma (MCL). Their potential

Review of Literature
30 mechanisms of action against MCL cells were investigated, both
alone and in combination with rituximab. In one study,
their potential mechanisms of action against MCL cells were
investigated, both alone and in combination with
rituximab. Thalidomide, lenalidomide and rituximab have no direct
effect on MCL cell viability. However, both immunomodulatory
drugs indirectly affect viability by enhancing peripheral blood
mononuclear cell-mediated cytotoxicity, with lenalidomide inducing
significantly higher levels of toxicity thanthalidomide. Rituximab
induces both complement-dependent and antibody-dependent
cellular cytotoxicity (ADCC) against MCL cells. Rituximab-induced
ADCC is enhanced by lenalidomide and, to a lesser
extent,thalidomide. Preliminary in vivo findings in MCL patients
treated with thalidomide support a role for natural killer cells in the
efficacy of these drugs.
Aggressive and highly aggressive lymphomaa
• Diffuse large B-cell lymphoma
The cure rate of DLBCL with initial therapy has dramatically
improved with the use of anthracycline-based regimens, as well as
the addition of the anti-CD20 monoclonal antibody, rituximab (Sehn
et al., 2005). Standard R-CHOP uses the combination of rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone.
However, approximately 10% of patients with DLBCL will be
refractory to primary therapy, and up to 40% of patients who
initially respond to primary therapy will relapse within 2 – 5 years of
diagnosis (Coiffier, 2002).

Review of Literature
31 Many clinical, biochemical, and cytogenetic markers have
been shown to be predictive of higher rates of relapse. These include
bone marrow, testicular, and sinonasal involvement, high
international prognostic index (IPI) score, and overexpression of bcl-
2 (Shivakumar and Armitage, 2006). Studies utilizing gene
expression profiling have consistently demonstrated that patients
with DLBCL arising from germinal center B cells have a better
prognosis than those of activated or post-germinal center origin
(Alizadeh et al., 2000) ; however, this may not be the case with
relapsed or refractory disease (Moskowitz et al., 2005).
Many chemotherapy regimens have demonstrated efficacy in
relapsed or primary refractory disease. In the late 1980s and 1990s,
autologous stem cell transplantation (ASCT) following
chemotherapy was established as the preferred treatment over
chemotherapy alone in those patients who are candidates for
aggressive therapy and have disease that remains chemotherapy
responsive. For those patients who are not candidates for ASCT, the
goal of therapy is to palliate symptoms of the disease with minimal
chemotherapy-induced morbidity (Philip et al., 1987).
1. Salvage therapy regimens for relapsed refractory diffuse large
B-cell lymphoma
In the past 30 years, multiple regimens for DLBCL have been
developed for patients with relapsed or refractory disease. The goal
of these salvage regimens is to maximize tumor response in
preparation for ASCT for those patients who are candidates for

Review of Literature
32 aggressive therapy, while preserving the ability to harvest stem cells
(Philip et al., 1995).
Although a number of regimens have documented activity in
relapsed DLBCL, there is no current standard of care. However, the
addition of rituximab to combination chemotherapy has been shown
to improve complete response (CR) rates and therefore is often used
in salvage therapy. Rituximab, ifosfamide, carboplatin, and
etoposide (R-ICE) is a common salvage regimen used for second-
line treatment before ASCT. The initial report of ICE in transplant-
eligible patients with relapsed NHL demonstrated an overall
response rate (ORR) of 66.3%, including a CR rate of 24%. With the
addition of rituximab to this regimen, the CR rate increased from
24% to 53%, with no significant increase in toxicity. In the long
term, Results to date are very preliminary but suggest encouraging
rates of response (Moskowitz et al., 2005).
Combination therapies including cytarabine and cisplatin have
also commonly been used to treat relapsed DLBCL. Dexamethasone,
cytarabine, and cisplatin (DHAP) was used in the landmark PARMA
trial, which demonstrated the superiority of ASCT in the
management of relapsed aggressive NHL (Philip et al., 1995). Trials
of DHAP in combination with rituximab have demonstrated similar
to improved activity, with no significant additional toxicity (Witzig
et al., 2008). More recently, R-DHAX was found efficient regimen
in patients with relapsed/refractory B-cell NHL even in elderly
patients if hematologic toxicities are closely managed (Lignon et al.,
2010).

Review of Literature
33 Etoposide, methylprednisone, cytarabine and cisplatin
(ESHAP) also uses the combination of an antimetabolite with a
platinum agent but adds the topoisomerase inhibitor, etoposide.
Results of this infusional regimen have shown a CR rate of 37% and
a PR rate of 27%; however, in this trial there was a mixed population
of patients treated with low-, intermediate- and high-grade
lymphoma (Velasquez et al., 1994). R-ESHAP has been
demonstrated to have significant activity in relapsed or refractory
DLBCL, with an ORR of 73%, including 45% complete or uncon-
firmed complete responses (CR/Cru). Of note, prior exposure to
rituximab resulted in lower overall response rates, lower
progression-free survival (PFS) and overall survival (OS) after the
combination of R-ESHAP and ASCT (Martin et al., 2008).
Regimens utilizing the cytarabine analog, gemcitabine, have
been developed based on documented single-agent activity and
tolerability. Gemcitabine and cisplatin have been combined with
dexamethasone (GDP) or methylprednisolone (GEM-P), with ORRs
of 62 and 67%, respectively (Sirohi et al., 2007). Rituximab,
gemcitabine and oxaliplatin (R-Gem-Ox) is a third regimen to use
gemcitabine and a platinum agent in combination. When combined
with rituximab, this regimen has produced response rates of 82% in
patients treated for DLBCL. Hematologic toxicities were common in
the above combinations of chemotherapeutic regimens; however, the
majority of patients had adequate stem cell collection for ASCT (El-
Gnaoui et al., 2007).

Review of Literature
34 There are salvage regimens that, like first-line treatment,
include anthracycline chemotherapy, which raises concern for
progressive cardiotoxicity. Many patients being treated for relapsed
DLBCL may already have received up to 400 mg/m2 of
doxorubicin. The incidence of congestive heart failure (CHF) has
been well documented to rise with increasing the aggregate dose of
anthracycline. Estimates of the rates of CHF are 0.14% in patients
who have received 400 mg/m2, 7% at doses of 550 mg/m2, and >
18% when the cumulative anthracycline doses exceed 700 mg/m2
(Von Hoff et al., 1979).
Etoposide, prednisone, vincristine, doxorubicin and
cyclophosphamide (EPOCH) and mesna, ifosfamide, mitoxantrone,
etoposide (MINE) can be used in the salvage setting. Despite the
increased cumulative dose of the anthracycline agent, few cardiac
toxicities have been reported in studies of patients with higher
anthracycline exposure (Wilson et al., 2002). MINE achieved an
ORR of 48%, including a CR rate of 21%, which included patients
treated as third-line therapy after cisplatin and cytarabine for
relapsed disease (Rodriguez et al., 1995).
Rituximab has also been combined with MINE prior to stem
cell collection and appeared to be active as a pre-ASCT regimen
(Emmanouilides et al., 2002). For EPOCH, the CR rate has been in
the range of 24 – 27% in patients with relapsed and refractory
aggressive lymphomas (Gutierrez et al., 2000). Rituximab-EPOCH
can be safely administered to patients with pretreated NHL, and
appears to have increased response rates in Phase II trials (Jermann
et al., 2004).

Review of Literature
35 There are multiple combinations of chemotherapy used in the
treatment of relapsed and refractory DLBCL. The initial decision
point following relapse of DLBCL has been to determine whether
the patient is a transplant candidate. It is important to note that the
benefit of ASCT was established prior to the use of rituximab,
leading to some debate as to the role of transplantation in the era of
rituximab-based front-line therapy. For patients eligible to consider
transplant, common regimens include R-ICE, R-DHAP and R-Gem
combinations. Phase III studies to evaluate the optimal platinum-
based regimen are ongoing. In patients who are not eligible for
transplantation, both single-agent and combination regimens are
available for palliation. Monoclonal antibodies have become an
important part of the treatment of DLBCL, as discussed above. In
addition to combinations with chemotherapy, rituximab has activity
as a single agent in relapsed aggressive lymphoma. Coiffier and
colleagues (1998) randomized patients to two dose regimens of
rituximab, 375 or 500 mg/m2 weekly × 8, and found an ORR of 37%
and a median time to progression (TTP) of 8 months.
There was no apparent benefit for the higher dose of rituximab
over the standard dose. The treatment was very well tolerated, with
largely infusion-related toxicity, suggesting that this may be a
reasonable palliative treatment. Weekly paclitaxel has also shown
activity in treating relapsed and refractory DLBCL. CR rates have
been reported at 20%, with overall minimal toxicity to the patients;
myelosuppression was seen in 20% of study patients (Rizzieri et al.,
2004).
Recently, a risk-adapted treatment approach was evaluated.
After two cycles of DHAP, patients received high-dose treosulfan/

Review of Literature
36 etoposide/ carboplatinum (TEC) and autologous stem cell rescue.
After TEC, low-risk patients with late relapse (>1 year after first CR
who achieved CR after DHAP received no further treatment.
Patients with late relapse who achieved CR or PR only after TEC
underwent a second cycle of TEC. High-risk patients with early
relapse/refractory disease received treosulfan/fludarabine followed
by allogeneic transplantation. Rituximab was added in patients with
B-cell lymphoma (86%). At entry, 36% of all 57 patients had
refractory disease, 32% early and 32% late relapse.
During DHAP treatment, progression occurred in 32% of patients.
Of 33 patients who received TEC, 5 received second TEC and 15
allogeneic transplantation. Main toxicity after TEC was oral
mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In
total, 42% patients achieved CR. Median OS was 21.4 months for all
patients and 32.6 for those who underwent allogeneic
transplantation. International prognostic index (IPI) at study entry
was highly discriminative at predicting OS (P<0.0001). The authors
concluded that risk-adapted, treosulfan-based therapy with auto- and
allo-SCT is feasible. Long-term survival is possible with allogeneic
transplantation (Koenigsmann et al., 2014).
2. Haematopoietic stem cell transplantation
HSCT is recommended in patients with relapsed NHL. HSCT
currently does not have a well-defined role in the primary therapy
for aggressive lymphomas but may be considered for high-risk
patients who achieve a CR to initial conventional chemotherapy
(Greb et al., 2007).

Review of Literature
37 However, the late effects of transplantation need to be
considered because the risk of myelodysplastic syndrome and acute
myeloid leukaemia is significant (Howe et al., 2003). Because of the
poor response rates and outcomes reported to date, autologous
HSCT is not recommended in primary refractory or relapsed
aggressive NHL not responding to salvage chemotherapy (Josting et
al., 2005).
Alternative treatment strategies are required in these cases,
and, wherever possible, patients should be enrolled in clinical trials
assessing new treatment regimens and novel therapeutic agents.
Allogeneic HSCT is potentially curative due to its graft versus
lymphoma effect, hence should be considered in younger patients
with relapsed disease or highly aggressive lymphomas (Vey et al.,
2006). However, the benefits of lower relapse rates are abrogated by
higher treatment-related mortality (Ingram et al., 2008).
The use of nonmyeloablative or reduced-intensity allogeneic
transplants has significantly decreased the early treatment related
mortality and can increase the number of patients eligible for
allogeneic HSCT (Sorror et al., 2008).
Recent efforts to improve the outcome of HSCT in NHL by
reducing relapse include the addition of radioimmunoconjugates to
conditioning regimens and the use of rituximab for ‘‘in vivo
purging ’’ around the time of stem cell harvesting and also as
adjuvant therapy after SCT (Dreyling et al., 2007).

Review of Literature
38 Chemoimmunotherapy
In many centers, younger and fit patients often receive initial
treatment with R-CHOP or with the R-Hyper CVAD/methotrexate –
cytarabine regimen. Accumulating evidence suggests that the
inclusion of high-dose cytarabine may be an important part of initial
therapy. Induction therapy may be consolidated with ASCT, which
increases PFS but has not yet been proven to improve OS. Older
individuals and those with significant comorbid illness receive
lower-intensity front-line treatment. As a result, chemoimmunot-
herapy in the relapsed setting typically employs a single agent or
combination with the aim of disease control and symptom resolution
while avoiding excess toxicity. Several newer combination regimens
for relapsed MCL have been reported recently, with others in
ongoing clinical trials (Geisler et al., 2008; van et al., 2009).
The regimen of rituximab, fludarabine, cyclophosphamide and
mitoxantrone (R-FCM) was shown to provide significantly higher
response rates in relapsed MCL as compared with FCM alone in a
randomized Phase III trial. Responding patients in this study
underwent a second randomization to maintenance rituximab
(weekly × 4 doses of 375 mg/m2 given 3 and 9 months post
completion of FCM or R-FCM) versus observation. The duration of
response did not differ significantly for those patients receiving
rituximab maintenance (12 vs 14 months), although more patients in
the maintenance arm remained in remission after 2 years follow-up
(45 vs 9%) (Forstpointner et al., 2006).

Review of Literature
39 Cladribine, like fludarabine, is also a purine nucleoside
analogue with activity in MCL. Among 24 patients with recurrent
disease (none with prior therapy with a nucleoside analogue), 11
(46%) responded to cladribine given as a 2-h infusions days 1 – 5 of
each 4-week cycle. Five patients (21%) achieved CR. Patients
responding after two cycles received a total of four to six cycles.
Median time to progression was only 5.4 months, with almost a third
of patients progressing while on therapy. Toxicity included grade 3 –
4 neutropenia in 50% and thrombocytopenia in 17% of patients. The
addition of rituximab improved responses and duration of response
when used in combination with cladribine as initial MCL therapy
without increased cytopenias, suggesting that it may also enhance
responses in relapsed patients (Inwards et al., 2008).
Gemcitabine has single-agent activity in the relapse setting,
and has been used in combination with dexamethasone (DG) and
DG plus cis-platinum (PDG) as well as rituximab and oxaliplatin
(GEMOX-R). With small numbers of patients treated thus far,
responses were observed in about one-third of DG patients, half of
PDG and in 85% of GEMOX-R, including 64% CR. Grade 3 – 4
thrombocytopenia was the major toxicity observed with these
regimens (Rodriguez et al., 2007).
An interesting regimen for relapsed MCL is PEPC, which
combines oral prednisone, etoposide, procarbazine and
cyclophosphamide. Dosing is given on a daily schedule until
leukopenia occurs, followed by a titrated dosing schedule after
recovery of counts. Among 22 patients with heavily pretreated MCL,

Review of Literature
40 an ORR of 82% and CR rate of 46% were observed, with an
acceptable toxicity profile. It is proposed that this ‘metronomic ’
therapy via a prolonged, low-dose oral schedule may overcome
chemotherapy resistance (Coleman et al., 2008).
PEPC has been modified by the addition of rituximab and low-
dose thalidomide, each of which has single-agent activity including
proposed enhancement of antiangiogenesis. This RT-PEPC regimen
is now being evaluated in a Phase II US multicenter trial (Ruan et
al., 2008).
Novel agents
Given the uniform overexpression of cyclin D1 (or, in rare
cases, cyclin D2 or D3) in MCL, and mutations in other cell cycle
regulatory proteins or expression, targeting the cell cycle regulatory
pathway is a logical treatment strategy. Flavopiridol, an inhibitor of
cyclin D/CDK4 and cyclin D/CDK6 complexes, promotes apoptosis
via downregulation of mcl-1 and XIAP and inhibits proliferation in
vitro in a variety of cancer types (Schwartz and Shah, 2005).
A number of flavopiridol dosing and schedule approaches
have been utilized to enhance response and modify the frequent side
effects of diarrhea, nausea and vomiting. A Canadian Phase II study
tested a daily bolus schedule for 3 consecutive days every 3 weeks in
30 evaluable patients with relapsed (n = 19) or untreated (n = 11)
MCL. Three patients achieved PR and 20 stable disease for an
average duration of 3.4 months (range, 1.4 – 10.3) (Kouroukis et al.,
2003).

Review of Literature
41 More recently, Lin et al., (2010) conducted a phase I study
of flavopiridol, fludarabine, and rituximab (FFR) in patients with
mantle-cell lymphoma (MCL), indolent B-cell non-Hodgkin's
lymphomas (B-NHL), and CLL to determine the activity of FFR.
Overall response rate was 82% (complete response, 50%;
unconfirmed complete response, 5%; partial response, 26%),
including 80% of patients with MCL (median age, 68; seven
complete responses, one partial response). Median progression-free
survival (PFS) was 25.6 months. Median PFS of patients with
nonblastoid variant MCL (n = 8) was 35.9 months.
Ligustrazine as a salvage agent in combination with
chemotherapy can elevate response rate, prolong PFS with
manageable toxicity in relapsed or refractory NHL (Yang and Jiang,
2010).
• Peripheral T-cell lymphoma
Although standard treatment has generally been with CHOP or
other anthracycline-containing chemotherapy, there is little
information from randomized clinical trials to support treatment
decisions in the majority of non-cutaneous T-cell NHL (Greer,
2006).
Because of the lack of success with frontline chemotherapy
regimens in PTCL, the majority of patients will relapse and require
additional therapy. As with DLBCL, the general approach to
relapsed disease is second-line chemotherapy, with or without high-
dose therapy with ASCT. In contrast to B-cell lymphoma, however,
randomized trials have not been performed to evaluate the

Review of Literature
42 effectiveness of these therapies. The available information comes
from retrospective reviews or Phase II studies, most of which are
small and include a broad spectrum of T-cell diseases. A number of
experiences with ASCT in relapsed PTCL have been published,
although all are either single-arm prospective trials or retrospective
reviews. The Stanford group recently published long-term results of
ASCT for PTCL at their center, with a median follow-up of 5 years.
Disease status at the time of transplant was important, with a 5-year
OS of 76% for those in first CR or PR, but only 30 – 40% in those
with refractory disease or in second CR or PR. Based on this and
other retrospective analyses, it appears that consolidative ASCT in
first remission may have the best chance of prolonging survival
(Chen et al., 2008).
One large trial evaluated ASCT after four to six cycles of
CHOP in 83 patients with PTCL. Altogether, 66% of patients
responded to CHOP chemotherapy and went on to ASCT. The
estimated 3-year OS was 48% for all patients, 71% for patients who
underwent ASCT, and 11% for those who did not have the ASCT
(Reimer et al., 2009).
A number of studies have evaluated the activity of ASCT in
relapsed PTCL. Kewalramani and colleagues (2006) retrospectively
compared the outcome of 24 patients with relapsed or refractory
PTCL to that of 86 patients with relapsed DLBCL. The 5-year PFS
and OS for the PTCL patients were 24 and 33%, respectively, which
were not significantly different from those of the DLBCL patients.

Review of Literature
43 A larger retrospective study has been done by the GEL-TAMO
(Spanish Lymphoma/Autologous Bone Marrow Transplant Study
Group). This study included 123 patients with relapsed PTCL, 91%
of whom had chemosensitive disease at the time of relapse. Five-
year PFS and OS were 34 and 45%, respectively, suggesting that a
significant proportion of patients with chemosensitive disease at the
time of relapse can achieve long-term disease-free survival
(Rodriguez et al., 2007).
A retrospective study of ASCT in Korean patients with PTCL
included 36 patients with relapsed or refractory disease, with similar
results. For those patients with relapsed or refractory disease, the 3-
year PFS and OS were 46 and 33%, respectively. Although these
results were inferior to those of patients transplanted in first
remission, they provide further evidence for the role for ASCT in
relapsed and refractory PTCL. For patients who are not candidates
for ASCT at the time of relapse, there are insufficient data to guide
therapy. Studies of salvage chemotherapy regimens have often
included too few PTCL patients to make conclusions. In studies of
subsequent ASCT, chemotherapy regimens have included ICE,
DHAP, EPOCH, ESHAP and Gem-based therapies. There are no
comparative trials available in relapsed PTCL, but available
evidence would suggest that regimens used in DLBCL are
reasonable options in patients with relapsed or refractory PTCL. It is
clear that novel approaches are needed for the treatment of PTCL
(Yang et al., 2009).

Review of Literature
44 Prochazka et al., (2011) showed that intensive first-line
therapy with etoposide-doxorubicine-based regimens and ASCT
consolidation may lead to long-term disease control in about a half
of patients with chemosensitive PTCL. Achievement PET negativity
is probably an essential prerequisite for long-term complete
remission.
II. Surgical management
Surgery is useful only in selected situations, most commonly
to establish a diagnosis by obtaining a biopsy specimen. Because
lymphoma is a systemic illness, resection of the sites of disease is
used only in selected situations. Surgery may be particularly useful
in primary GI lymphomas when the disease is localized or when
there is a risk of perforation (Yoon et al., 2004). Orchiectomy is
commonly the initial treatment for patients with testicular lymphoma
(Zuca et al., 2003).
Prognostic factors
Prognostic features are related to the disease and the individual
patient. NHLs are divided into indolent or aggressive lymphomas
based on their natural history of growth. Indolent lymphomas have a
relatively slow rate of growth but have a low potential for cure with
currently available treatments. Median survival is measured in years
to decades. Examples of indolent lymphomas include grade I and II
follicular lymphoma, chronic lymphocytic leukemia/small
lymphocytic lymphoma, marginal zone lymphoma (B-cell), and
mycosis fungoides. Follicular lymphoma comprises 35% of adult
NHL in the United States and 22% worldwide (Ganti et al., 2005).

Review of Literature
45 Clinically, most patients are elderly and present with an
advanced stage of disease. Median survival is approximately 8 to 10
years. Indolent lymphomas can transform into high-grade
malignancies in approximately 30% of patients (Winter et al., 2004).
Treatment for transformed lymphoma is similar to that of aggressive
lymphomas but the outcomes are less favorable. The aggressive
lymphomas can be cured in approximately half of the cases
(Kasamon and Swinnen, 2004).
Examples of aggressive lymphomas are mantle cell
lymphoma, diffuse large B-cell lymphoma, follicular grade III
lymphoma, primary effusion lymphoma, adult Tcell leukemia/
lymphoma, extranodal natural killer/T-cell lymphoma nasal-type,
and angioimmunoblastic T-cell lymphoma, peripheral T-cell
lymphoma, and anaplastic large cell lymphomas. Diffuse large B-
cell lymphomas are the most frequent subtype of lymphoma. T-cell
lymphomas tend to have a poorer survival rate than aggressive B-
cell lymphomas. Highly aggressive B-cell lymphomas include
precursor B-lymphoblastic lymphoma/leukemia and Burkitt ’s
lymphoma. Prognostic indicators can predict outcome based on
clinical presentation and have been determined for aggressive
lymphomas as well as follicular lymphoma. The International
Prognostic Index (IPI) was developed to categorize aggressive NHL
on the basis of easily identifiable clinical features (International
Non-Hodgkin ’
s Lymphoma Prognostic Factor Project members,
1993).

Review of Literature
46 It is also applicable to other types of lymphoma; however, its
validity in AIDS related lymphoma is not well established. Factors
in this model include age, stage, number of extranodal sites, LDH,
and performance status. An age adjusted model for patients under
the age of 60 years has also been developed and includes stage,
performance status, and LDH. The Follicular Lymphoma
International Prognostic Index (FLIPI) is a model that has been
devised for follicular lymphoma (Solal-Celigny et al., 2004).

Patients and Methods
47 Patients and Methods
The present study is a retrospective and prospective study. It
was conducted at Medical Oncology Department, Zagazig
University and Fakous Oncology Center from July, 2007 through
July, 2012. Approval from Zagazig University Institutional Review
Board was Achieved.
Patients
Five hundred patients were included in the study. They were
selected according to the following criteria:
• Inclusion criteria
o Age ≥ 16 years.
o Histopathologically proved NHL.
o Residence in Sharqia Governorate.
• Exclusion criteria
o Age < 16 years.
o Residence outside Governorate.
o Deficient patients' records.
METHODS
All patients were subjected the following:
A. Careful history taking
B. Thorough clinical examination

Patients and Methods
48 The clinical details noted in these cases included: age, gender,
site of involvement, presenting clinical features and the presence of
extranodal involvement.
C. Laboratory investigations
• Routine laboratory investigations
Hemoglobin, total and differential leucocyte count, platelet
count, peripheral smear study for abnormal cells, etc), and
biochemical (liver function tests, urea, creatinine, uric acid.
• Pathological investigations
o The diagnosis of lymphoma was established by biopsy from
lymph nodes or involved tissues. The patients were
classified on the basis of histopathologic diagnosis
according to Working Formulation (National Cancer
Institute, 1982).
o Bone marrow aspiration was done if favorable. The staging
of the patients were done by Ann Arbor staging system
(Avivi et al., 2005).
• Radiological Investigations
o CT neck.
o CT Chest.
o CT Abdomen and pelvis.

Patients and Methods
49
Statistical analysis

Data obtained from the present study were computed using
SPSS versions 17 under the platform of Microsoft Windows XP,
Professional Edition. Continuous data were expressed in the form of
mean ± SD while categorical data were expressed in the form of
count and percent. Survival analysis was achieved using Kaplan
Meyer analysis.

Results
50 Results
Results of the present study are shown in the following tables
and figures:

A. All patients
1. Demographic characteristics of the studied patients (n=500)
The studied patients had a mean age of 43.5 ± 13.4. They
included 332 males (66.4 %) and 168 females (33.6 %) (Table-1).
Table-1 Demographic characteristics of the studied patients
(n=500)
Range 20.0 – 72.0
Age (years)
Mean ± SD 43.5 ± 13.4
Male 332 (66.4 %)
Sex
Female 168 (33.6 %)
66% 34%
Male Female

Fig. (1) Sex distribution in the studied patients

Results
51 2. Clinical manifestations in the studied patients (n=500)
Clinical manifestation in the studied patients included B
symptoms in 214 patients (42.8 %), fatigue in 267 patients (53.4 %),
anorexia in 243 patients (48.6 %), dyspnea in 17 patients (3.4 %), ,
abdominal and /or chest pain in 123 patients (24.6 %), bleeding
manifestations in 24 patients (4.8 %), lymphadenopathy in 465
patients (93.0 %), splenomegaly in 250 patients (50.0 %) and
hepatomegaly in 204 patients (40.8 %) (Table-2).

Table-2 Clinical manifestations in the studied patients (n=500)
No %
B symptoms 214 42.8
Fatigue 267 53.4
Anorexia 243 48.6
Dyspnoea 17 3.4
Abdominal and /or chest pain 123 24.6
Bleeding manifestations 24 4.8
Lymphadenopathy 465 93.0
Splenomegaly 250 50.0
Hepatomegaly 204 40.8

Results
52 3. Viral hepatitis infection in the studied patients
In the studied patients, it was found that 104 patients are HCV
+ve (20.8 %) while 46 patients (9.2 %) are HBV +ve and 5 patients
had HCV and HBV infections (table-3)

Table-3 Viral infection in the studied patients (n=500)
No %
HCV 104 20.8
HBV 46 9.2
HCV + HBV 5 1.0

Results
53 4. Tumor grading in the studied patients
In the present study, 339 patients (67.8 %) had aggressive
NHL, while 121 patients (24.2 %) had indolent disease and 40
patients (8.0 %) had highly aggressive disease (Table-4)

Table-4 Tumor grading in the studied patients (n=500)
N %
Indolent 121 24.2
Aggressive 339 67.8
Highly aggressive 40 8.0

24.2% 8.0%
67.8%
Indolent Aggressive Highly aggressive

Fig. (2) Tumor grade in the studied patients

Results
54
5. Pathological varieties of the studied cases
The pathological varieties in the studied patients included
diffuse large B-cell lymphoma in 249 patients (49.8 %), follicular
lymphoma in 80 patients (16.0 %), small lymphocyte lymphoma in
40 patients (8.0 %), mantle cell lymphoma in 42 patients (8.4 %),
peripheral T-cell lymphoma in 42 patients (8.4 %), marginal zone B-
cell lymphoma in 7 patients (1.4 %), Burkitt ’s lymphoma in 22
patients (4.4 %) and lymphoblastic lymphoma in 18 patients (3.6 %)
(Table-5).
Table-5 Pathological varieties of the studied patients (n=500)
N %
Diffuse large B-cell lymphoma 249 49.8
Follicular lymphoma 80 16.0
Small lymphocyte lymphoma 40 8.0
Mantle cell lymphoma 42 8.0
Peripheral T-cell lymphoma 42 8.4
Marginal zone B-cell lymphoma 7 1.4
Burkitt ’s lymphoma 22 4.4
Lymphoblastic lymphoma 18 3.6

Results
55 6. Tumor stages in the studied patients
In the present study, tumor stages include stage I in 57 patients
(11.4 %), stage II in 96 patients (19.2 %), stage III in 208 patients
(41.6 %), Stage IV in 139 patients (24.0 %) (Table-6).

Table-6 Tumor stages in the studied patients (n=500)
N %
Stage I 57 11.4
Stage II 96 19.2
Stage III 208 41.6
Stage IV 139 24.0

41.6% 19.2% 27.8% 11.4%
Stage I Stage II Stage III Stage IV

Fig. (3) Tumor stages in the studied patients

Results
56 7. Nodal status in the studied patients
This table shows that nodal affection in 465 patients (93.0 %)
and extranodal affection in 162 patients (32.4 %). Among patients
with extranodal affection, 149 patients (29.8 %) had one extranodal
site and 13 patients (2.6 %) had 2 extranodal sites (Table-7)

Table-7 Nodal status in the studied patients (n=500)
N %
Nodal 465 93.0
Extranodal 162 32.4

Results
57 8. Nodal involvement in the studied patients
In the present study, nodal affection comprised cervical LN in
258 patients (51.6 %), axillary LN in 356 patients (71.2 %), inguinal
LN in 330 patients (66.0 %), mediastinal LN in 102 patients (20.4
%) and abdominal LN in 378 patients (75.0 %), (table-8).

Table-8 Nodal involvement in the studied patients (n=465)
No %
Cervical 258 51.6
Axillary 356 71.2
Inguinal 330 66.0
Mediastinal 102 20.4
Abdominal 378 75.6

Results
58 9. Extranodal involvement in the studied patients
Extranodal involvement in the studied patients included
stomach affection in 23 patients (4.6 %), bowel affection in 56
patients (11.2 %), skin affection in 33 patients (6.6 %), spleen
affection in 53 patients, testicular affection in 4 patients (0.8 %),
ovarian affection in 4 patients (0.8 %) and CNS affection in 2
patients (0.4 %) (Table-9).

Table-9 : Extranodal involvement in the studied patients (n=90)
N %
Stomach 23 4.6
Skin 33 6.6
Bowel 56 11.2
Spleen 53 10.6
Testicular 4 0.8
Ovarian 4 0.8
CNS 2 0.4

Results
59 10. BM involvement in the studied patients (n=500)
In the studied patients there 105 patients (21.0 %) BM +ve
while 395 patients (79.0 %) were BM –ve (table-10).
No %
BM +ve 105 21.0
BM -ve 395 79.0

11. Laboratory data in the studied patients (n=500)
The laboratory findings in the studied patients included +ve
LDH in 234 patients, anemia in 200 patients (40.0 %) and elevated
ESR in 170 patients (34.0%), leucopenia in 150 patients (30.0 %),
elevated liver enzymes in 40 patients (8.0 %), thrombocytopenia in
20 patients (4.0 %) (Table-11).
Table-11 Laboratory data in studied patients (n=500)
No %
LDH +ve 234 46.8
Anemia 200 40.0
Leucopenia 150 30.0
Elevated ESR 170 34.0
Elevated liver enzymes 40 8.0
Thrombocytopenia 20 4.0

Results
60 12. IPI in the studied patients
According to the IPI, 184 patients (36.8 %) were at low risk
while 155 patients (31.0 %) were at low-intermediate risk, 126
patients (31.3 %) were at high-intermediate risk and 35 patients (7.0
%) were at high risk (table-12).

Table-12 IPI in the studied patients (n=500)
N %
Low-risk 184 36.8
Low-intermediate risk 155 31.0
High-intermediate risk 126 25.2
High risk 35 7.0

Results
61 13. Treatment regimen in the studied patients
The treatment regimen in the studied patients were CHOP in
331 patients (66.2 %), COP in 116 patients (23.2 %), HYPER-
CVAD in 48 patients (9.6 %) and splenectomy in 5 patients (1.0 %)
(Table-13).
Table-13 Treatment regimen in the studied patients (n=500)
N %
COP 116 23.2
CHOP 331 66.2
HYPER-CVAD 48 9.6
Splenectomy 5 1.0

Results
62 14. Treatment response in the studied patients
Treatment response in the studied patients included partial
remission in 170 patients (34.0 %), complete remission in 269
patients (53.8 %), progressive disease in 44 patients (8.8 %) and
stable disease in 17 patients (3.4 %). Among the studied patients, 99
(19.8 %) had relapse and 100 (20.0 %) died (Table-14).

Table-14 Treatment response in the studied patients (n=500)
N %
Complete remission 262 52.4
Partial remission 177 35.4
Progressive disease 44 8.8
Stable disease 17 3.4
Relapse 99 19.8
Death 100 20.0
53%
35% 3% 9%
Complete remission Partial remission Progressive disease Stable disease

Fig. (4) Treatment response in the studied patients

Results
63 B. Patients with indolent NHL
15. Demographic characteristics of the studied patients (n=121)
The studied patients had a mean age of 45.0 ± 15.3. They
included 81 males (66.4 %) and 40 females (33.6 %) (Table-15).

Table-15 Demographic characteristics of the studied patients
(n=121)
Range 20.0 – 72.0
Age (years)
Mean ± SD 43.7 ± 13.8
Male 81 (66.7 %)
Sex
Female 40 (33.3 %)

67% 33%
Male Female

Fig. (5) Sex distribution in the studied patients

Results
64 16. Clinical manifestations in the studied patients
Clinical manifestation in the studied patients include B
symptoms in 51 patients (42.1 %), fatigue in 75 patients (62.0 %),
anorexia in 54 patients (44.6 %), dyspnea in 3 patients (2.5%),
abdominal and /or chest pain in 33 patients (27.3 %), bleeding
manifestations in 5 patients (4.1 %), lymphadenopathy in 118
patients (97.5 %), splenomegaly in 98 patients (19.6%) and
hepatomegaly in 52 patients (10.4 %) (Table-16).

Table-16 Clinical manifestations in the studied patients (n=121)
No %
B symptoms 51 42.1
Fatigue 75 62.0
Anorexia 54 44.6
Dyspnoea 3 2.5
Abdominal and /or chest pain 33 27.3
Bleeding manifestations 5 4.1
Lymphadenopathy 118 97.5
Splenomegaly 98 19.6
Hepatomegaly 52 10.4

Results
65 17. Viral hepatitis infection in the studied patients
In the studied patients, it was found that 23 patients are HCV
+ve (19.0 %) while 12 patients (9.9 %) are HBV +ve with 2 patients
having both HCV and HBV (1.7 %) (table-17)

Table-17 Viral hepatitis infection in the studied patients (n=121)
No %
HCV 23 19.0
HBV 12 9.9
HCV + HBV 2 1.7

Results
66 18. Pathological varieties of the studied cases
The pathological varieties in the studied patients included
follicular lymphoma in 40 patients (33.1 %), small lymphocyte
lymphoma in 40 patients (33.1 %), mantle cell lymphoma in 34
patients (28.1 %), peripheral T-cell lymphoma in 42 patients (8.4 %)
and marginal zone B-cell lymphoma in 7 patients (5.8 %) (Table-
18).
Table-18 Pathological varieties of the studied cases (n=121)
N %
Follicular lymphoma 40 33.1
Small lymphocyte lymphoma 40 33.1
Mantle cell lymphoma 34 28.1
Marginal zone B-cell lymphoma 7 5.8

Results
67 19. Tumor stages in the studied patients
In the present study, tumor stages include stage I in 21 patients
(17.4 %), stage II in 30 patients (24.8 %), stage III in 41 patients
(33.9 %), Stage IV in 29 patients (24.0 %) (Table-19).

Table-19 Tumor stages in the studied patients (n=121)
N %
Stage I 21 17.4
Stage II 30 24.8
Stage III 41 33.9
Stage IV 29 24.0

17.4%24.0%
33.9% 24.8%
Stage I Stage II Stage III Stage IV

Fig. (6) Tumor stages in the studied patients

Results
68 20. Nodal status in the studied patients
This table shows that nodal affection in 118 patients (97.5 %)
and extranodal affection in 32 patients (26.4 %) (Table-20)
Table-20 Nodal status in the studied patients (n=121)
N %
Nodal 118 97.5
Extranodal 32 26.4

21. Nodal involvement in the studied patients
In the present study, nodal affection comprised cervical LN in
69 patients (57.0 %), axillary LN in 34 patients (28.1 %), inguinal
LN in 41 patients (33.9 %), mediastinal LN in 21 patients (17.4 %)
and abdominal LN in 27 patients (22.3 %), (table-21).
Table-21 Nodal involvement in the studied patients (n=121)
No %
Cervical 69 57.0
Axillary 34 28.1
Inguinal 41 33.9
Mediastinal 21 17.4
Abdominal 27 22.3

Results
69 22. Extranodal involvement in the studied patients
Extranodal involvement in the studied patients in the studied
patients included stomach affection in 3 patients (2.5 %), bowel
affection in 13 patients (10.7 %), skin affection in 4 patients (3.3 %),
ovarian affection in 2 patients (1.7 %) and CNS affection in 2
patients (0.4 %) (Table-22).
Table-22 Extranodal involvement in the studied patients (n=121)
N %
Stomach 3 2.5
Skin 4 3.3
Bowel 13 10.7
Spleen 11 9.1
Ovarian 2 1.7

23. BM involvement in the studied patients
In the present study, 27 patients (22.3 %) were BM +ve while
94 patients (77.7 %) were BM –ve (table-23)

Table-23 BM involvement in the studied patients (n=121)
No %
BM +ve 27 22.3
BM -ve 94 77.7

Results
70 24. Laboratory data in the studied patients (n=212)
The laboratory findings in the studied patients included +ve
LDH in 55 patients (45.5 %), anemia in 50 patients (41.3 %)
leucopenia in 35 patients (28.9 %), elevated ESR in 10 patients (8.3
%) and thrombocytopenia in 5 patients (4.1 %) (Table-24).

Table-24 Laboratory data in studied patients (n=121)
No %
LDH +ve 55 45.5
Anemia 50 41.3
Leucopenia 35 28.9
Elevated ESR 10 8.3
Thrombocytopenia 5 4.1

Results
71 25. IPI in the studied patients
According to the IPI, 55 patients (45.5 %) were at low risk
while 37 patients (30.6 %) were at low-intermediate risk, 20 patients
(16.5 %) were at high-intermediate risk and 9 patients (7.4 %) were
at high risk (Table-25)
Table-25 IPI in the studied patients (n=121)
N %
Low-risk 55 45.5
Low-intermediate risk 37 30.6
High-intermediate risk 20 16.5
High risk 9 7.4

26. Treatment regimen in the studied patients
The treatment regimen in the studied patients were COP in 116
patients (95.9 %), and splenectomy in 2 patients (1.7 %) (Table-26).

Table-26 Treatment regimen in the studied patients (n=n=121)
N %
COP 116 95.9
Splenectomy 2 1.7

Results
72 27. Treatment response in the studied patients
Treatment response in the studied patients included partial
remission in 39 patients (32.2 %), complete remission in 68 patients
(56.2 %), progressive disease in 9 patients (7.4 %) and stable disease
in 5 patients (4.1 %). 20 patients (16.5 %) had relapse and 24
patients (19.8 %) died (Table-27).

Table-27 Treatment response in the studied patients (n=121)
N %
Complete remission 65 56.2
Partial remission 42 34.7
Progressive disease 9 7.4
Stable disease 5 4.1
Relapse 20 16.5
Death 24 19.8

57% 4% 7%
32%
Complete remission Partial remission Progressive disease Stable disease

Fig. (7) Treatment response in the studied patients

Results
73
B. Patients with aggressive NHL
28. Demographic characteristics of the studied patients
The studied patients had a mean age of 44.8 ± 15.1. They
included 231 males (68.1 %) and 108 females (31.9 %) (Table-28).
Table-28 Demographic characteristics of the studied patients
(n=339)
Range 20.0 – 72.0
Age (years)
Mean ± SD 43.3 ± 13.3
Male 231 (68.1 %)
Sex
Female 108 (31.9 %)

68% 32%
Male Female

Fig. (8) Sex distribution in the studied patients

Results
74 29. Clinical manifestations in the studied patients
Clinical manifestation in the studied patients include B
symptoms in 146 patients (43.1 %), fatigue in 202 patients (59.6 %),
anorexia in 170 patients (50.1 %), dyspnea in 12 patients (3.5%),
abdominal and /or chest pain in 77 patients (22.7 %), bleeding
manifestations in 18 patients (5.3 %), lymphadenopathy in 311
patients (91.7 %), splenomegaly in 127 patients (25.4 %) and
hepatomegaly in 135 patients(27.0%) (Table-29).

Table-29 Clinical manifestations in the studied patients (n=339)
No %
B symptoms 146 43.1
Fatigue 202 59.6
Anorexia 170 50.1
Dyspnoea 12 3.5
Abdominal and /or chest pain 77 22.7
Bleeding manifestations 18 5.3
Lymphadenopathy 311 91.7
Splenomegaly 127 25.4
Hepatomegaly 135 27.0

Results
75 30. Viral hepatitis infection in the studied patients
In the studied patients, it was found that 67 patients are HCV
+ve (19.8 %) while 30 patients (8.8 %) are HBV +ve and 2 patients
(0.6 %) had HCV + HBV (table-30)

Table-30 Viral hepatitis infection in the studied patients (n=339)
No %
HCV 67 19.8
HBV 30 8.8
HCV + HBV 2 0.6

Results
76 31. Pathological varieties of the studied cases
The pathological varieties in the studied patients included
Diffuse Large Cell B lymphoma in 249 patients (73.5 %) follicular
lymphoma in 40 patients (11.8 %), mantle cell lymphoma in 8
patients (2.4 %) and peripheral T-cell lymphoma in 42 patients (12.4
%) (Table-31).

Table-31 Pathological varieties of the studied cases (n=339)
N %
Diffuse Large Cell B lymphoma 249 73.5
Follicular lymphoma 40 11.8
Mantle cell lymphoma 8 2.4
Peripheral T-cell lymphoma 42 12.4

Results
77 32. Tumor stages in the studied patients
In the present study, tumor stages include stage I in 30 patients
(8.8 %), stage II in 60 patients (17.7 %), stage III in 153 patients
(45.1 %), Stage IV in 96 patients (28.3 %) (Table-32).
Table-32 Tumor stages in the studied patients (n=339)
N %
Stage I 30 8.8
Stage II 60 17.7
Stage III 153 45.1
Stage IV 96 28.3

45.1%17.7% 8.8%
28.3%
Stage I Stage II Stage III Stage IV

Fig. (9) Tumor stages in the studied patients

33. Nodal status in the studied patients

Results
78 This table shows that nodal affection in 311 patients (91.7 %)
and extranodal affection in 118 patients (34.8 %) (Table-33)
Table-33 Nodal status in the studied patients (n=339)
N %
Nodal 311 91.7
Extranodal 118 34.8

34. Nodal involvement in the studied patients
In the present study, nodal affection comprised cervical LN in
151 patients (44.5 %), axillary LN in 97 patients (28.6 %), inguinal
LN in 118 patients (34.8 %), mediastinal LN in 69 patients (20.4 %)
and abdominal LN in 86 patients (25.4 %), (table-34).

Table-34 Nodal involvement in the studied patients
No %
Cervical 151 44.5
Axillary 97 28.6
Inguinal 118 34.8
Mediastinal 69 20.4
Abdominal 86 25.4

Results
79 35. Extranodal involvement in the studied patients
Extranodal involvement in the studied patients in the studied
patients included stomach affection in 17 patients (5.0 %), bowel
affection in 39 patients (11.5 %), spleen affection in 40 patients
(11.8 %), skin affection in 25 patients (7.4 %), testicular affection in
3 patients (0.9 %), ovarian affection in 2 patients (0.6 %) (Table-35).

Table-35 Extranodal involvement in the studied patients (n=339)
N %
Stomach 17 5.0
Skin 25 7.4
Bowel 39 11.5
Spleen 40 11.8
Testicular 3 0.9
Ovarian 2 0.6

36. BM involvement in the studied patients
In the present study, 63 patients (18.6 %) were BM +ve while
276 patients (81.4%) were BM –ve (table-36)
Table-36 BM involvement in the studied patients (n=339)
No %
BM +ve 63 28.3
BM -ve 276 71.7

Results
80 37. Laboratory data in the studied patients (n=339)
The laboratory findings in the studied patients included +ve
LDH in 160 patients (52.8 %), anemia in 130 patients (38.3 %)
leucopenia in 100 patients (29.5 %), elevated ESR in 110 patients
(32.4 %), elevated liver enzymes in 25 patients (7.4 %) and
thrombocytopenia in 12 patients (3.5 %) (Table-37).

Table-37 Laboratory data in studied patients (n=339)
No %
LDH +ve 160 52.8
Anemia 130 38.3
Leucopenia 100 29.5
Elevated ESR 110 32.4
Elevated liver enzymes 25 7.4
Thrombocytopenia 12 3.5

Results
81 38. IPI in the studied patients
According to the IPI, 114 patients (33.6 %) were at low risk
while 106 patients (31.3 %) were at low-intermediate risk, 99
patients (29.2 %) were at high-intermediate risk and 20 patients (5.9
%) were at high risk (Table-38)

Table-38 IPI in the studied patients (n=339)
N %
Low-risk 114 33.6
Low-intermediate risk 106 31.3
High-intermediate risk 99 29.2
High risk 20 5.9

39. Treatment regimen in the studied patients
The treatment regimen in the studied patients were CHOP in
331 patients (97.6 %), and HYPE-RCVAD in 8 patients (2.4 %)
(Table-39).

Table-39 Treatment regimen in the studied patients (n=500)
N %
CHOP 331 97.6
HYPE-RCVAD 8 2.4

Results
82 40. Treatment response in the studied patients
Treatment response in the studied patients included complete
remission in 173 patients (51.0 %), partial remission in 125 patients
(36.9 %), progressive disease in 32 patients (9.4 %) and stable
disease in 10 patients (2.9 %). 65 patients (19.2 %) died and 68
patients (20.1 %) had relapse (Table-40).

Table-40 Treatment response in the studied patients (n=339)
N %
Complete remission 173 51.0
Partial remission 123 36.3
Progressive disease 33 9.7
Stable disease 10 2.9
Relapse 68 20.1
Death 65 19.2

51%
36% 3% 10%
Complete remission Partial remission Progressive disease Stable disease

Fig. (10) Treatment response in the studied patients

Results
83
C. Patients with highly aggressive NHL
41. Demographic characteristics of the studied patients
The studied patients had a mean age of 44.2 ± 14.0. They
included 20 males (50.0 %) and 20 females (50.0 %) (Table-41).
Table-41 Demographic characteristics of the studied patients
(n=40)
Range 20.0 – 72.0
Age (years)
Mean ± SD 44.2 ± 14.0
Male 20 (50.0 %)
Sex
Female 20 (50.0 %)

50% 50%
Male Female

Fig. (11) Sex distribution in the studied patients

Results
84 42. Clinical manifestations in the studied patients
Clinical manifestation in the studied patients include B
symptoms in 17 patients (42.5 %), fatigue in 20 patients (50.0 %),
anorexia in 19 patients (47.5 %), dyspnea in 2 patients (5.0%),
abdominal and /or chest pain in 13 patients (32.5 %), bleeding
manifestations in 1 patient (2.5 %), lymphadenopathy in 36 patients
(90.0 %), splenomegaly in 25 patients (5.0 %) and hepatomegaly in
17 patients (3.4 %) (Table-42).

Table-42 Clinical manifestations in the studied patients (n=40)
No %
B symptoms 17 42.5
Fatigue 20 50.0
Anorexia 19 47.5
Dyspnoea 2 5.0
Abdominal and /or chest pain 13 32.5
Bleeding manifestations 1 2.5
Lymphadenopathy 36 90.0
Splenomegaly 25 5.0
Hepatomegaly 17 3.4

Results
85 43. Viral hepatitis infection in the studied patients
In the studied patients, it was found that 14 patients are HCV
+ve (35.0 %) while 4 patients (10.0 %) are HBV +ve. One patients
had HCV + HBV (table-43)

Table-43 Viral infection in the studied patients (n=40)
No %
HCV 14 35.0
HBV 4 10.0
HCV + HBV 1 2.5

44. Pathological varieties of the studied cases
The pathological varieties in the studied patients included
Burkitt ’s lymphoma in 22 patients (55.0 %) and lymphoblastic
lymphoma in 18 patients (45.0 %) (Table-44).

Table-44Pathological varieties of the studied cases (n=40)
N %
Burkitt ’s lymphoma 22 55.0
Lymphoblastic lymphoma 18 45.0

Results
86 45. Tumor stages in the studied patients
In the present study, tumor stages include stage I in 6 patients
(15.0 %), stage II in 6 patients (15.0 %), stage III in 14 patients (35.0
%), Stage IV in 14 patients (35.0.3 %) (Table-45).

Table-45 Tumor stages in the studied patients (n=40)
N %
Stage I 6 15.0
Stage II 6 15.0
Stage III 14 35.0
Stage IV 14 35.0

35.0% 15.0%15.0%
35.0%
Stage I Stage II Stage III Stage IV

Fig. (5) Tumor stages in the studied patients

Results
87 46. Nodal status in the studied patients
This table shows that nodal affection in 36 patients (90.0 %)
and extranodal affection in 12 patients (30.0 %) (Table-46)

Table-46 Nodal status in the studied patients (n=40)
N %
Nodal 36 90.0
Extranodal 12 30.0

47. Nodal involvement in the studied patients
In the present study, nodal affection comprised cervical LN in
22 patients (55.0 %), axillary LN in 13 patients (32.5 %), inguinal
LN in 11 patients (27.5 %), mediastinal LN in 12 patients (30.0 %)
and abdominal LN in 9 patients (22.5 %), (table-47).
Table-47 Nodal involvement in the studied patients (n=40)
No %
Cervical 22 55.0
Axillary 13 32.5
Inguinal 11 27.5
Mediastinal 12 30.0
Abdominal 9 22.5

Results
88 48. Extranodal involvement in the studied patients
Extranodal involvement in the studied patients in the studied
patients included stomach affection in 3 patients (7.5 %), bowel
affection in 4 patients (10.0 %), spleen affection in 2 patients (5.0 %)
skin affection in 4 patients (10.0 %), spleen affection in 2 patients
(5.0 %) , testicular affection in 1 patients (2.5 %) and CNS affection
in 2 patients (Table-48).

Table-48 Extranodal involvement in the studied patients (n=40)
N %
Stomach 3 7.5
Skin 4 10.0
Bowel 4 10.0
Spleen 2 5.0
Testicular 1 2.5
CNS 2 5.0

Results
89 49. BM involvement in the studied patients
In the present study, 12 patients (30.0 %) were BM +ve while
28 patients (70.0 %) were BM –ve (table-49)

Table-49 BM involvement in the studied patients (n=40)
No %
BM +ve 12 30.0
BM -ve 28 70.0

50. Laboratory data in the studied patients (n=40)
The laboratory findings in the studied patients included +ve
LDH in 19 patients (47.5 %), anemia in 35 patients (87.5 %)
leucopenia in 10 patients (25.0 %), elevated ESR in 15 patients (37.5
%), elevated liver enzymes in 5 patients (12.5 %) and
thrombocytopenia in 3 patients (7.5 %). (Table-50).
Table-50 Laboratory data in studied patients (n=40)
No %
LDH +ve 30 75.0
Anemia 35 87.5
Leucopenia 10 25.0
Elevated ESR 15 37.5
Elevated liver enzymes 5 12.5
Thrombocytopenia 3 7.5

Results
90 51 IPI in the studied patients
According to the IPI, 15 patients (37.5 %) were at low risk
while 12 patients (30.0 %) were at low-intermediate risk, 7 patients
(17.5 %) were at high-intermediate risk and 3 patients (7.5 %) were
at high risk (Table-51)

Table-51 IPI in the studied patients (n=40)
N %
Low-risk 15 37.5
Low-intermediate risk 12 30.0
High-intermediate risk 7 17.5
High risk 6 15.0

52. Treatment regimen in the studied patients
The treatment regimen in the studied patients was HYPE-
RCVAD in 40 patients (100.0 %) (Table-52).
Table-49 Treatment regimen in the studied patients (n=40)
N %
HYPE-RCVAD 40 100.0

Results
91 53. Treatment response in the studied patients
Treatment response in the studied patients included complete
remission in 30 patients (75.0 %), partial remission in 6 patients
(15.0 %), progressive disease in 2 patients (5.0 %) and stable disease
in 2 patients (5.0 %). 11 patients (27.5 %) had relapse and 11
patients (27.5 %) died (Table-53).
Table-53 Treatment response in the studied patients (n=40)
N %
Complete remission 30 75.0
Partial remission 6 15.0
Progressive disease 2 5.0
Stable disease 2 5.0
Relapse 11 27.5
Death 11 27.5
2; 5%
60%30% 5%
Complete remission Partial remission Progressive disease Stable disease

Fig. (13) Treatment response in the studied patients

Discussion
92 Discussion
NHL is a heterogeneous group of lymphoid neoplasms
classified by morphology, clinical behavior and genetic features.
There is some evidence that the different sub-groups of NHL have
different epidemiological features (Massenburg et al., 2008). There
has been a rapid increase in the incidence of NHL worldwide
(Aggarwal et al., 2011).
The reasons for these increases remain poorly understood
because very few risk factors, apart from severe immunodeficiency,
have been identified for NHL. This underscores the importance of
ongoing surveillance and epidemiological studies of this group of
diseases. The rise in prevalence might be due to the increasing
availability of medical tools that enhance the sensitivity and
specificity of NHL diagnosis, particularly among older people;
indeed, older people showed the greatest increase in prevalence
(Eltom et al., 2002 ).
The aim of the present study is to describe the demographic,
clinical, pathological and laboratory findings in NHL patients in
Sharqia Governorate including Zagazig University Hospitals and
Faqous Oncology Center. The therapeutic regimens and outcome are
also be discussed.
To achieve this target, 500 hundred patients with NHL were
included in the study. They had a mean age of 43.5 ± 13.4 years in
agreement with the study of Castella et al., (2001) from United Arab

Discussion
93 Emirates who reported a mean age 43 years in their study. Our study
included 332 males (66.4 %) and 168 females (33.6 %) (2:1). This is
in agreement with the study of Ameen et al., (2010) from Kuwait
who also found that observed a male preponderance, with a
male/female ratio of 2:1.
In the present study, 93% of the patients with NHL had
lymphadenopathy. Mandal et al., (2011) , in agreement with our finding,
found that lymphadenopathy is the commonest clinical sign and was
found in 94.74% of the patients with NHL , In the present study, nodal
affection comprised abdominal LN (75.0 %), axillary LN (71.2 %)
and inguinal LN (66.0 %). This is in harmony with findings of
Ibrahim et al., (2012) who reported the same three groups as the
most commonly affected groups in their study.
In our study, 53.4% of the NHL patients had fatigue. Husson et
al. (2015) estimated the prevalence of fatigue in 716 Dutch patients with
NHL and found that 43% of these patients feel fatigue The presence as
well as level of fatigue was found to be associated with many factors
including duration since diagnosis, age of the patients, gender,
comorbidity and educational level . In the current study, 50% of the
patients had splenomegaly. It was previously reported that spenomegaly
is often a manifestation of the NHL (Li et al., 2013; Sun and
Juskevicius, 2012) . In addition, Paes et al. (2010) notes that spleen can
affected in 20% of the patients with NHL. However, spleen can be of
normal size despite tumor infiltration and only a sector of these patients
may had splenomegaly at time of presentation (Even-Sapir et al., 2007) .
Among the NHL patients in this study, 40.8% had hepatomegaly. Paes et
al. (2010) noted that hepatic involvement in NHL is less common than

Discussion
94 splenic involvement and in most cases of secondary hepatic involvement.
B symptoms were found in 42.8 % of the patients. Mandal et al., (2011)
reported that B symptoms were noted in 63.16% cases of their NHL
patients.
The current study revealed extranodal affection in 32.4 % of
patients. Among patients with extranodal affection, 2.6 % had more
than one extranodal site. This figure is close to that found by the
former study of Abdel-Fattah et al., (2007) who noted that 37.9 %
of the studied patients had extranodal involvement while in the study
of Almasri et al., (2004) , extranodal involvement was noted in 42.3
%. This discrepancy may be explained by the different sample size
and selection criteria.
Extranodal involvement in the studied patients included bowel
affection in 11.2 % of patients. This is in agreement with
Economopoulos et al., (2005) who aimed to to illustrate the
clinicopathological features of non-Hodgkin ’s lymphoma (NHL) and
reported the bowel as the most commonly affected extranodal site.
In our study, it was found that 20.8 % of patients are HCV +ve
while 9.2 % patients are HBV +ve and 1 % of patients had
coinfection with HCV and HBV. This is in agreement with the study
of Mele et al., (2003) who found that HCV prevalence was 17.5%
among the 400 lymphoma patients. On the other hand, the
prevalence of hepatitis B surface antigen (HBsAg) among newly
diagnosed NHL patients was 5.72% and of HCV 1.84 % in the study
of Grudeva-Popova et al., (2013). This differences is explained by
the variable characteristics of the studied patients as this study was

Discussion
95 performed in Italy; a country with lower prevalence of HCV in
comparison with Egypt.
In the studied patients there were 21% of patients BM +ve
while 79 % of patients were BM –ve. This is in agreement with the
study of Kittivorapart and Chinthammitr (2011) . Incidence of BM
affection was noted in 24.4% of the studied patients.
In the present study, LDH was elevated in 36.8% of the patients.
Lu et al. (2015) reported that LDH was elevated in 90% of the NHL
patients. All the patients included in that study (n=29) had liver
involvement which may account for the high rate of elevated LDH. Lin et
al. (2015) found that 48.8% of the NHL patients had elevated LDH. The
frequency of elevated LDH cases is fewer than that found by Abdelhamid
et al., (2013) . This is explained by the higher frequency of advanced
disease in the present study in comparison to that of Abdelhamid et al.,
(2013) .
Other laboratory data included anemia in 41.3 % of patients
and thrombocytopenia in 4.1 % of patients in agreement with the
study of Ferrario et al., (2012).
In the present study, 67.8 % of patients had aggressive NHL,
while 24.2 % of patients had indolent disease and 8.0 % of patients
had highly aggressive disease. This is in agreement with the study of
Mandal et al., (2011). In their study, aggressive lymphoma
constituted the commonest type of NHL followed by indolent NHL
and highly aggressive NHL.

Discussion
96 The most common pathological subtyp in the studied patients
was diffuse large B-cell lymphoma in 249 patients (49.8 %). This is
in harmony with the Egyptian study of Abdel-Fattah et al., (2007).
In their study, diffuse large B-cell lymphoma was the most
encountered pathological variety in the 2638 patients study.
Our study declared that tumor stages included stage I in 11.4
%, stage II in 19.2 %, stage III in 41.6 %, Stage IV in 24.0 % of
patients. This differs from the study of Economopoulos et al.,
(2005) . In their study, stage I was noted in 21.6 % of patients, stage
II was found in 23.7 % of patients, stage III in 16.5 % and stage IV
in 38.1 %. The variation may be explained by the different
populations of the two studies.
According to the IPI, 36.8 % of patients were at low risk while
31.0 % of patients were at low-intermediate risk. This is in
agreement with the study of Wu et al., (2014) who examined the
association between serum β2-M and the prognosis of NHL and
analyzed its predictive value. In their study, the majority of patients
had an IPI index of ≤ 2.0 (low-risk to low-intermediate risk), Lin et
al. (2015) found that 40.9% of the NHL patients had IPI score > 3.
Treatment response in the studied patients included complete
remission in 53.8 % of patients, partial remission in 34.0 % of
patients, This is agreement with the study of Wö
hrer et al., (2005).
In their study, the overall response was 84% (61% complete
response, 23% partial response).

Discussion
97 Among the studied patients, 19.8 % had relapse and 20.0 %
died. These figures are similar to what found by Abdelhamid et al.,
(2011) who reported that 18 % of patients died and differ from the
same study in the relapse rate which was 32.2 %.
In patients with indolent lymphoma, the studied patients
included 81 males (66.4 %) and 40 females (33.6 %). This agrees
with the study of Blum et al. (2006) . In their study males markedly
outnumbered females.
Among our patients, 62% had fatigue, This varied from results of
the study of Kuzul et al., (2007) , In their study, fatigue was the most
common clinical presentation followed by nauseas, vomiting and fever.
This difference is attributed to genetic and epidemiological characteristics
of the studied patients. while 42.1% of our patients had B symptoms,
Hoppe et al (2013) reported that 20% of the patients had B symptoms at
presentation.
In the current study, nodal affection was noted in 118 patients
(97.5 %) and extranodal affection in 32 patients. And this matched
with the study of Papageorgiou et al., (2005). frequency of
extranodal affection is fewer than observed by the study of Blum et
al., (2006).
In the studied patients, it was found that 23 patients are HCV
+ve (19.0 %) while 12 patients (9.9 %) are HBV +ve with 2 patients
having both HCV and HBV (1.7 %). The association
between hepatitis C virus (HCV) infection and B-cell non-Hodgkin's
lymphomas (NHL) has been demonstrated by epidemiological

Discussion
98 studies, in particular in highly endemic geographical areas such as
Italy, Japan, and southern parts of United States. In these countries,
together with diffuse large B-cell lymphomas, marginal zone
lymphomas are the histotypes most frequently associated with HCV
infection; in Italy around 20-30% cases of marginal zone lymphomas
are HCV positive (Arcaini et al., 2012) and Andersen et al. (2015) ,
studied the risk of NHL in a cohort of 4345 patients infected with HBV
and found that 3.6% of the HBV +ve patients had indolent NHL and the
incidence rate ratio for this occurrence was 1.2.
The pathological varieties in the studied patients included
follicular lymphoma in 33.1 % of patients and small lymphocyte
lymphoma in 33.1 % of patients. This is in agreement with the study
of Kuzel et al., (2007). In their study, most patients had small
lymphocyte lymphoma and follicular lymphoma.
In the present study, tumor stages include stage I in (17.4 %),
stage II in (24.8 %), stage III (33.9 %), Stage IV in (24.0 %). This
distribution is differs from that found by Chan et al., (2011) . In
their study stage distribution ranged from (24.0 %) in stage 1 to
(15.0 %) in stage 2 (24.0 %) in stage 3 and (29.0 %) in stage 4. The
variation may be explained by the different populations of the two
studies
In our study, according to the IPI, 45.5 % of patients were at
low risk while 30.6 % of patients were at low-intermediate risk. This
agrees with the study of Kuzzel et al., (2006). In their study, the
majority of patients had an IPI of ≤ 2.0.

Discussion
99 Treatment response in the studied patients included complete
remission in 56.2 % of patients, partial remission in 32.2 % of
patients, progressive disease in 7.4 % of patients and stable disease
in 4.1 % of patients; 16.5 % had relapse 19.8 % died. Hoppe et al
(2013) reported that the complete remission is common among these
patients with the use of R-COP. Use of COP in treatment of patients
with indolent NHL was reported by the study of Herold et al.,
(2006) . In their study, complete response was achieved in 20 %,
while partial response was achieved in 56.0 % of patients. The study
revealed that 20 % had relapse with no mortality. The low mortality
rate may be explained by the relative young age in their study.
In patients with aggressive lymphoma, the studied patients
included 231 males (68.1 %) and 108 females (31.9 %). This is in
harmony with the study of Kasamon et al., (2009) . In their study,
there was a marked male predominance.
As regards the clinical manifestations in our patients at time of
presentation, fatigue was the most common finding accounted for 59.6%
of the patients. The notable presentation of fatigue in those patients was
also noted by the study of Jensen et al. (2013) . In their study, patients
with aggressive lymphoma experienced marked fatigue when compared
with other controls. The presentation of patients with aggressive
lymphoma with fatigue was also reported by Tajima et al. (2014) .
The most common pathological subtype in the studied patients
included diffuse large cell B lymphoma in 73.5% of the patients.
Issa et al (2015) reported that the diffuse large cell B lymphoma was
the most prevalent variety among the patients with aggressive

Discussion
100 lymphoma which is in agreement with our findings. Also, in
agreement with our findings Hohloch et al., (2014) found that
diffuse large cell b lymphoma constituted that majority of their
aggressive lymphoma series.
In the present study, tumor stages in patients with aggressive NHL
revealed that patients with stage III and IV comprised 73.4 % of the
studied patients which is higher than the former study of Hohloch et al.,
(2014) who noted that stage III and IV were the most commonly
represented stages in their series.
In the present study, LDH was elevated in 52.8 % of patients
of aggressive NHL. This figure is lower than that found by the study
of Kasamon et al., (2009) who found elevated LDH in 39 out of 59
patients included in their study (65.0 %). This may be attributed to
the smaller sample size of their study.
According to the IPI, most patients in our study had an IPI ≤
3.0 ( 33.6% of our patients were at low risk while 31.3% were at low-
intermediate risk) . This is harmony with the study of Gustafson et al.,
(2014) . In their study, the majority of patients had IPI ≤ 3.0.
Treatment response in most patients treated with CHOP
regimen in the present study included complete response in 51.0 %
of patients while the study of Hohloch et al., (2014) complete
response rate was 76.4 %. In the present study, relapse was found in
20.1 % of patients and death in 19.2 %. In the study of Kasamon et
al., (2009) out of 28 patients included, six relapsed (21.4 %). Four of

Discussion
101 these had died (14.1 %). This differences of death rate may be
explained by smaller size of his study.
In patients with highly aggressive NHL , the studied patients
included 30 males (75.0 %) and 10 females (25.0 %). This higher
percentage of male distribution comes in agreement with Ribera et al.,
(2013), Thomas et al., (2006) and Van Imhoff et al., (2005) who
reported a male to female ratio [2.5:1, 3.4:1 and 3.5:1 respectively] .
Clinical manifestations in the studied patients included B
symptoms in 17 patients (42.5 %) in comparison to 25.0 % in the
study of Kian et al., (2008).
In the studied patients there were 37.5% of patients BM +ve
while 62.5 % of patients were BM –ve. This is in agreement with the
study of Hoelzer (2002) , Incidence of BM affection was noted in
31% of the studied patients.
The pathological varieties in the studied patients included
Burkitt ’s lymphoma in 22 patients (55.0%) , Lymphoblastic
lymphoma in 18 patients (45.0%)
As regards tumor sating in the present study, 35% were in stage
III, and 35% were in stage IV. This differs from the study of Riad et al.,
(2014) who reported that 60.7% had stage III and 21.4% had stage IV
disease. The difference may be attributed to the different sample size .
LDH was found to be elevated in 75% of the patients in the current
study. This is in agreement with many previous studies that reported that
LDH was elevated in 80% (Wildes et al., 2014), 75% (Intermesoli et al.,

Discussion
102 2013), 71% (Barnes et al., 2011) , 60% (Diviné et al., 2005) and in 83%
(Lee et al., 2001) of the patients enrolled in these studies .
According to the IPI 7.5 % were at high risk. This differs with
the study of Riad et al., (2010) who found that most patients had a
high risk disease may be due to higher stages.
The treatment regimen in the studied patients was HYPE-RCVAD
in all of these patients. Treatment response in the studied patients
included complete remission in 75% of the patients, partial remission in
15% and progressive disease in 5%., In agreement with our findings
Hong et al. (2015) found that R-hyper-CVAD showed excellent
treatment outcomes in adult patients with Burkitt lymphoma with 75% of
the patients in that study achieved complete remission. and In
comparison, Lee et al., (2001) enrolled 30 patients of Burkitt's lymphoma
in his study and CR was obtained in 83% of the patients, 7% had PR and
7% PD, Also, an earlier study of Wä
sterlid et al. (2013) found that hyper-
CVAD achieved a complete remission in 82% of the patients with
Burkitt's lymphoma.

Summary and Conclusions
103 Summary
The aim of the present study is to describe the demographic,
clinical, pathological and laboratory findings in NHL patients in
Sharqia Governorate including Zagazig University Hospitals and
Faqous Oncology Center. The therapeutic regimens and outcome
will also be discussed.
To achieve this target, 500 hundred patients with NHL were
included in the study. In the present study, the clinical presentations
included lymphadenopathy in 465 patients (93.0 %), B symptoms in
214 patients (42.8 %), fatigue in 267 patients (53.4 %), anorexia in
243 patients (48.6 %), dyspnea in 17 patients (3.4 %), , abdominal
and /or chest pain in 123 patients (24.6 %), bleeding manifestations
in 24 patients (4.8 %), splenomegaly in 35 patients (7.0 %) and
hepatomegaly in 25 patients (5.0 %) .
In our study, it was found that 104 patients are HCV +ve (20.8
%) while 46 patients (9.2 %) are HBV +ve and 5 patients had HCV
and HBV infections.
In the present study, 339 patients (67.8 %) had aggressive
NHL, while 121 patients (24.2 %) had indolent disease and 40
patients (8.0 %) had highly aggressive disease.
The pathological varieties in the studied patients included
diffuse large B-cell lymphoma in 249 patients (49.8 %), follicular
lymphoma in 80 patients (16.0 %), small lymphocyte lymphoma in
40 patients (8.0 %), mantle cell lymphoma in 42 patients (8.4 %),

Summary and Conclusions
104 peripheral T-cell lymphoma in 42 patients (8.4 %), marginal zone B-
cell lymphoma in 7 patients (1.4 %), Burkitt ’s lymphoma in 22
patients (4.4 %) and lymphoblastic lymphoma in 18 patients (3.6%).
Our study declared that tumor stages included stage I in 57
patients (11.4 %), stage II in 96 patients (19.2 %), stage III in 208
patients (41.6 %), Stage IV in 139 patients (24.0 %).
In the present study, nodal affection comprised cervical LN in
258 patients (51.6 %), axillary LN in 356 patients (71.2 %), inguinal
LN in 330 patients (66.0 %), mediastinal LN in 102 patients (20.4
%) and abdominal LN in 378 patients (75.0 %).
The current study revealed extranodal affection in 162 patients
(32.4 %). Among patients with extranodal affection, 149 patients
(29.8 %) had one extranodal site and 13 patients (2.6 %) had 2
extranodal sites.
Extranodal involvement in the studied patients included
stomach affection in 23 patients (4.6 %), bowel affection in 56
patients (11.2 %), skin affection in 33 patients (6.6 %), spleen
affection in 53 patients, testicular affection in 4 patients (0.8 %),
ovarian affection in 4 patients (0.8 %) and CNS affection in 2
patients (0.4 %).
In the studied patients there 139 patients (27.8 %) BM +ve
while 361 patients (62.2 %) were BM –ve. In the present study, there
was elevated LDH in 234 patients (36.8 %). Other laboratory data

Summary and Conclusions
105 included anemia in 41.3 % of patients and thrombocytopenia in 4.1
% of patients.
According to the IPI, 184 patients (36.8 %) were at low risk
while 155 patients (31.0 %) were at low-intermediate risk, 126
patients (31.3 %) were at high-intermediate risk and 35 patients
(7.0%) were at high risk. This The treatment regimen in the studied
patients is similar to what found by Ibrahim et al., (2012) in his
study on Egyptian patients with NHL.
Treatment response in the studied patients included complete
remission in 269 patients (53.8 %), partial remission in 170 patients
(34.0 %), progressive disease in 44 patients (8.8 %) and stable
disease in 17 patients (3.4 %). Among the studied patients, 99 (19.8
%) had relapse and 100 (20.0 %) died.

Summary and Conclusions
106
Conclusions

• In the present study, 339 patients (67.8 %) had aggressive NHL,
while 121 patients (24.2 %) had indolent disease and 40 patients
(8.0 %) had highly aggressive disease.
• Treatment response in the studied patients included complete
remission in 269 patients (53.8 %), partial remission in 170
patients (34.0 %), progressive disease in 44 patients (8.8 %) and
stable disease in 17 patients (3.4 %).
• Among the studied patients, 99 (19.8 %) had relapse and 100
(20.0 %) died.

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اﻟﻌﺮﺑﻰ اﻟﻤﻠﺨﺺ
١اﻟﻌﺮﺑﻰاﻟﻤﻠﺨﺺ
اﻟﻠﻤﻔﺎوﯾﺔ اﻷورام اﻟﻐﯿﺮ ھﻮدﺟﯿﻜﻦ ﺗﺼﻨﻒ ﻣﺘﺠﺎﻧﺴﺔﻛ ﻏﯿﺮ ﻤﺠﻤﻮﻋﺔ ﻣﻦ اﻟﻠﻤﻔﺎوﯾﺔ اﻟﺨﻼﯾﺎ
اﻷورام ﮭﺎأﻧﻮاﻋو اﻷﺳﺎﺳﯿﺔ اﻟﻰ اﻟﺨﻠﯿﺔ ﺗﺄﺛﺮ ﺣﺴﺐ ﻋﻠﻰ ﺗﺼﻨﯿﻔﮭﺎ ﯾﺘﻢ : اﻟﻐﺪد ﺳﺮﻃﺎن
اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﺨﻠﯿﺔ) ب ( وھﻮ ﺷﯿﻮﻋﺎ،، اﻷﻛﺜﺮ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد وﺳﺮﻃﺎن اﻟﺨﻠﯿﺔ) ت ( .
ﻣﻦ اﻟﮭﺪف اﻟﺪراﺳﺔ ھﺬه :
وﺻﻒ ھﻮ واﻟﺪﯾﻤﻮﻏﺮاﻓﯿﺎاﻟﺴﺮﯾﺮﯾﺔاﻟﺨﺼﺎﺋﺺ واﻟﻨﺘﺎﺋﺞ ، اﻟﻤﻌﻤﻠﯿﺔ ﻣﺮﺿﻰﻓﻲ اورام
اﻟﻐﺪد ھﻮدﺟﯿﻜﻦ اﻟﻐﯿﺮ ﻣﺤﺎﻓﻈﺔاﻟﻠﯿﻤﻔﺎوﯾﺔ ﻓﻲ اﻟﺸﺮﻗﯿﺔ ﺑﺎﻟ اﻟﺠﺎﻣﻌﺔ ﻣﺴﺘﺸﻔﻰ ﺧﻼل زﻗﺎﺰﻣﻦ ﯾﻖ
ﻣﺮﻛﺰو سﻓﺎﻗﻮ ورامﻟﻸ . ﺳﯿﺘﻢ ﻛﻤﺎ ﻣﻨﺎﻗﺸﺔ ﻨﻈﻢاﻟ و اﻟﻨﺘﯿﺠﺔاﻟﻌﻼﺟﯿﺔ .
ﯿﻖوﻘﻟﺘﺤ اﻟﮭﺪف اﺬ،ھ درإ ﺗﻢجا ﺧﻤﺴﻤﺎﺋﺔ اﻟﻐﯿﺮ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺑﺄورام ﺾﻣﺮﯾ
ھﻮدﺟﯿﻜﻦ اﻟﺪراﺳﺔ ﺬهھ ﻓﻲﺖ وﺷﻤﻠ ، ا اﻟﺴﺮﯾﺮﯾﺔﻟﺨﺼﺎﺋﺺ اﻟﻠﻤﻔ ﺪﻘاﻟﻌ ﯾﺔﺎواﻋﺘﻼل ﻓﻲ ٥٦٤
ﺎﻀﻣﺮﯾ( ٠٫٣٩ ) ضوأﻋﺮا ، ) ﻰﺒاﻟ (ﻓﻲ ١٢٤ ﺎﻀﻣﺮﯾ ٤٢٨٫)٪( و ، ﺟﮭﺎدﻻﻓﻲا ٢٧٦
ﺎﻀﻣﺮﯾ ٤٫٣٥)٪( اﻟﺸﮭﯿﺔ ﺪانﻘوﻓ ، ٢ﻓﻲ٣٤ ﺎﻀﻣﺮﯾ ٦٫٨٤) ٪( ﺲاﻟﺘﻨﻔ وﺿﯿﻖ ، ﻓﻲ ١٧
ﺎﻀﻣﺮﯾ( ٪٤٫٣)، ﻦﺒﻄاﻟ ﻓﻲ مآﻻو / اﻟﺼﺪر أو ٢١ﻓﻲ٣ ﺎﻀﻣﺮﯾ ٢٦٫٤)٪( واﻟﻨﺰ ﻒﯾ،
ﻓﻲ ٢٤ ﺎﻀﻣﺮﯾ( ٪٨٫٤)، ﺤﺎلﻄاﻟ ﺨﻢﻀﺗ ٢ﻓﻲ٠٥ ﺎﻀﻣﺮﯾ ٠٥( %ﺪ ﺒاﻟﻜ ﺨﻢﻀوﺗ ،
٢ﻓﻲ٤٠ ﺎﻀﻣﺮﯾ ٨٫٠٤ %( .
دراﺳﺘﻨﺎ ،ﻓﻲ ﯿﻦﺒﺗ أن ١٤٠ ﺎﻀﻣﺮﯾ ﺳﻰ سﺑﻔﯿﺮو ﻣﺼﺎب %( ٢٨٫٠ ) ﺣﯿﻦ ﻓﻲ ان،
٦٤ ﺎﻀﻣﺮﯾ( ٫٩٢٪ )ﺑﻰﻣﺼﺎﺑﻮن سﺑﻔﯿﺮو و ٥ ﻣﺮﺿﻰ( ) ١٪٠ ﻣﻌﺎ ﺛﻨﯿﻦﻻﺑﺎ ﻣﺼﺎﺑﻮن .
اﻟﺪراﺳﺔ ﺬهھ ﻛﺎنﻓﻲ ، ٩٣٣ ﺎﻀﻣﺮﯾ ٨٫٧٦ )٪ ( عاﻟﻨﻮ اﻟﻌﺪواﻧﻲﻣﻦ ھﻮدﺟﯿﻜﻦاﻟﻐﯿﺮ ،
ﺣﯿﻦ ﻓﻲ ﻛﺎن ١٢١ ﺎﻀﻣﺮﯾ ٢٫٤٢ )٪ ( عاﻟﻨﻮ ﺨﺎزلاﻟﻤﺘﻣﻦ و ٠٤ ﺎﻀﻣﺮﯾ ٠٫٨)٪ ( ﻣﻦ
اﻟﻌﺪواﻧﯿﺔ ﺷﺪﯾﺪ عاﻟﻨﻮ .
ﺖوﺷﻤﻠ ﺻﻨﺎفاﻷ اﻟﻤﺮﺿﯿﺔ ﻓﻲ ﻟ اﻟﺨﺎﺿﻌﯿﻦ ﻠﺪراﺳﺔاﻟﻤﺮﺿﻰ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺳﺮﻃﺎن
) ﻰﺒاﻟ( ﻓﻲاﻟ ﺨﻠﯿﺔ ٢٩٤ ﺎﻀﻣﺮﯾ ٨٫٩٤)٪( ، اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺳﺮﻃﺎن ﻲﺒاﻟﺠﺮﯾ ﻓﻲ ٠٨
ﺎﻀﻣﺮﯾ ١٠٫٦)٪( ، اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺳﺮﻃﺎن اﻟﻠﻤﻔﺎوﯾﺎت ﺻﻐﯿﺮةﻓﻲ ٠٤ ﺎﻀﻣﺮﯾ( ٪٠٫٨ ) ،
اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺳﺮﻃﺎن اﻟﺨﻠﯿﺔ ءةﺎﺒﻋ ﻓﻰ٤٢ ﺎﻀﻣﺮﯾ( ٪٤٫٨) ، ﺮﻓﯿﺔﻄاﻟ اﻟ ﺳﺮﻃﺎن ﻐﺪد

اﻟﻌﺮﺑﻰ اﻟﻤﻠﺨﺺ
٢اﻟﻠﯿﻤﻔﺎوﯾﺔ )اﻟﺘﻰ (ﻓﻲاﻟ ﺨﻠﯿﺔ ٤٢ ﺎﻀﻣﺮﯾ( ٤٫٨٪)، ﺔﻄﻘﻣﻨ ھﺎﻣﺸﯿﺔ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺳﺮﻃﺎن
)ﻰﺒاﻟ( ﻓﻲ ﺧﻠﯿﺔ ٧ ﻣﺮﺿﻰ( ٪١٤٫)، وﺎﻟﻤﻔﮫﯾﺖﺑﯿﺮﻛ ﻓﻲ ٢٢ ﺎﻀﻣﺮﯾ( ٤٫٤٪ ) وﺳﺮﻃﺎن
اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ياﻟﻠﯿﻤﻔﺎو ﻓﻲ ١٨ ﺎﻀﻣﺮﯾ( ٦٫٣٪ . )
أﺖوﺿﺤ دراﺳﺘﻨﺎ أن ﻞﻣﺮاﺣ اﻟﻮرم ﺖﺷﻤﻠ اﻷوﻟﻰ اﻟﻤﺮﺣﻠﺔ ﻓﻲ ٧٥ ﺎﻀﻣﺮﯾ ١١٤٫)٪(،
اﻟﺜﺎﻧﯿﺔ اﻟﻤﺮﺣﻠﺔ ﻓﻲ٦٩ ﺎﻀﻣﺮﯾ ١٫٩٢)٪( ، ﻓﻲ اﻟﺜﺎﻟﺜﺔ اﻟﻤﺮﺣﻠﺔ ٢٨٠ ﺎﻀﻣﺮﯾ ٤١٦٫ )٪(،
اﻟﺮاﺑﻌﺔ اﻟﻤﺮﺣﻠﺔ ١ﻓﻲ٩٣ ﺎﻀﻣﺮﯾ ٢٠٫٤)٪ .(
ﻓﻲ اﻟﺪراﺳﺔ، ﺬهھ ةاﻟﻤﺘﺄﺛﺮ اﻟﻠﯿﻤﻔﺎوﯾﺔ ﺪﻘاﻟﻌ ﻢﻀﺗ ﯿﺔﻘاﻟﻌﻨ اﻟﻠﯿﻤﻔﺎوﯾﺔ ﺪﻘﻓﻲاﻟﻌ ٢٨٥ ﺎﻀﻣﺮﯾ
٥١٦٫)٪( ، ﺪﻘاﻟﻌ ﻹﯿاﻄﺔﺑ ﻓﻲ ٦٥٣ ﺎﻀﻣﺮﯾ ٧١٫٢)٪( ، اﻟﻠﯿﻤﻔﺎوﯾﺔ ﺪﻘرﺑﯿاﻟﻌ ﻹﺔا ﻓﻲ٠٣٣
ﺎﻀﻣﺮﯾ٠٫٦٦)٪( ، اﻟﻠﯿﻤﻔﺎوﯾﺔ ﺪﻘاﻟﻌ ﯿﺔاﻟﻤﻨﺼﻔ ١ﻓﻲ٠٢ ﺎﻀﻣﺮﯾ ٢٤٫٠)٪( و اﻟﻠﯿﻤﻔﺎوﯾﺔ ﺪﻘاﻟﻌ
ﻨﺒﻄﯿﺔاﻟ ﻓﻲ ٨٧٣ ﺎﻀﻣﺮﯾ ٠٫٥٧)٪ .(
ﺖﺑﯿﻨ وﻛﻤﺎ اﻟﺤﺎﻟﯿﺔ اﻟﺪراﺳﺔ ﺗﺄﺛﺮ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺎقﻄﻧ جاﻟﺨﺎر ١ﻓﻲ٦٢ ﺎﻀﻣﺮﯾ
)٣٢٪٤٫(. اﻟ اﻟﻤﺮﺿﻰ ﺑﯿﻦ ﻣﻦ ﯾﻌﺎﻧﻮن ﯾﻦﺬ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺎقﻄﻧ جاﻟﺨﺎر ﻛﺎن ١، ٩٤
ﺎﻀﻣﺮﯾ)٢٪٨٫٩( ﻓﻰ ﻊﻣﻮﻗ واﺣﺪ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺎقﻄﻧ جاﻟﺨﺎر ١و٣ ﺎﻀﻣﺮﯾ) ٢٪٦٫ ( ﻓﻰ
ﻣﻮﻗﻌﯿﻦ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺎقﻄﻧ جاﻟﺨﺎر .
ﻣﺸﺎرﻛﺔ ﻤﻦﻀوﺗ اﻟﻠﯿﻤﻔﺎوﯾﺔ اﻟﻐﺪد ﺎقﻄﻧ جاﻟﺨﺎر ﻟﻠﺪراﺳﺔ اﻟﺨﺎﺿﻌﯿﻦ اﻟﻤﺮﺿﻰ ﻓﻲ
ﻓﻲ ة٢اﻟﻤﻌﺪ ٣ ﺎﻀﻣﺮﯾ) ٪٦٫٤ (و، ﻓﻲ ءاﻷﻣﻌﺎ٦٥ ﺎﻀﻣﺮﯾ) ١١٫٢٪ ( ﻓﻲ اﻟﺠﻠﺪ ،٣٣
ﺎﻀﻣﺮﯾ)٪٦٫٦ ( ﻓﻲ ﺤﺎلﻄاﻟ ،٣٥ ﻓﻲ اﻟﺨﺼﯿﺔ و اﻟﻤﺮﺿﻰ ٤ ﻣﺮﺿﻰ) ٪٨٫٠ ( ﺾﯿﺒاﻟﻤ ،
ﻓﻲ٤ ﻣﺮﺿﻰ) ٪٨٫٠( وى اﻟﻤﺮﻛﺰ ﻰﺒاﻟﻌﺼ اﻟﺠﮭﺎز ﻓﻲ ٢ اﻟﻤﺮﺿﻰ) ٪٨٫٠ (.
كھﻨﺎ ﻟﻠﺪراﺳﺔ اﻟﺨﺎﺿﻌﯿﻦ اﻟﻤﺮﺿﻰ ١ﻓﻲ ٥٠ ﺎﻀﻣﺮﯾ) ١٢ ٪( اﻟﺸﻮﻛﻰ عاﻟﻨﺨﺎ ﯾﺠﺎﺑﻰإ
ﻛ ﺎنﺑﯿﻨﻤﺎ ٥٩٣ ﺎﻀﻣﺮﯾ) ٪٩٧( اﻟﺸﻮﻛﻰ عاﻟﻨﺨﺎ ﻰﺒﺳﻠ عارﺗﻔﺎ كھﻨﺎ ﻛﺎن اﻟﺪراﺳﺔ، ﺬهھ ﻓﻲ
دﯾﮭﯿﺪرﺟ ﻚﻛﺘﯿﻻزﺎﻨﯿ ﻓﻲ ٢٤٣ ﺎﻀﻣﺮﯾ) ٪٨٫٦٣ (. ىاﻷﺧﺮ ﺮﯾﺔﺒاﻟﻤﺨﺘ ﯿﺎﻧﺎتﺒاﻟ ﺖﻤﻨﻀوﺗ
ﻓﻲ اﻟﺪم ﺮﻘﻓ٤١٣٫ ﻓﻲ اﻟﺪﻣﻮﯾﺔ اﻟﺼﻔﯿﺤﺎت ﺺﻘوﻧ اﻟﻤﺮﺿﻰ ﻣﻦ ٫٤٪ اﻟﻤﺮﺿﻰ١ ﻣﻦ ٪ .
ﺎﻘاﻟﻌﺎﻟﻤﯿﺔووﻓ اﻟﺘﺸﺨﯿﺼﯿﺔ ﻞﻟﻠﻌﻮاﻣ ﻛﺎن ١، ٤٨ ﺎﻀﻣﺮﯾ) ٪٨٫٦٣ ( ﺾﻣﻨﺨﻔ ﺮﻄﺧ ﻓﻲ
ﻛﺎن ١ﺑﯿﻨﻤﺎ ٥٥ ﺎﻀﻣﺮﯾ) ٣١٪٠٫ ( وﻛﺎن اﻟﻤﺨﺎﻃﺮ، ﺾاﻟﻤﻨﺨﻔ ﻂاﻟﻤﺘﻮﺳ ٢١ﻓﻲ ٦ ﺎﻀﻣﺮﯾ
)٣١٪٣٫ ( كھﻨﺎ وﻛﺎن ﺔﻄاﻟﻤﺘﻮﺳ اﻟﻌﺎﻟﯿﺔ اﻟﻤﺨﺎﻃﺮ اتذ ﻓﻲ٥٣ ﺎﻀﻣﺮﯾ) ٪٠٫٧ ( ﻣﺨﺎﻃﺮ ﻓﻲ
ﻋﺎﻟﯿﺔ . ﻟﻠﺪراﺳﺔ اﻟﺨﺎﺿﻌﯿﻦ اﻟﻤﺮﺿﻰ ﻓﻲ جاﻟﻌﻼ اﻟﻨﻈﺎم اﺬھ

اﻟﻌﺮﺑﻰ اﻟﻤﻠﺨﺺ
٣ﺖﻤﻨﻀوﺗ جﻟﻠﻌﻼ ﺳﺘﺠﺎﺑﺔﻻا ﻓﻲ ﻟﻠﺪراﺳﺔاﻟ اﻟﺨﺎﺿﻌﯿﻦ ﻤﺮﺿﻰ ﻞﻛﺎﻣ ءﺷﻔﺎ ٢ﻓﻲ٩٦
ﺎﻀﻣﺮﯾ ٨٫٣٥) ٪( ، ءﺷﻔﺎ ﺟﺰﺋﻲ ١ﻓﻲ٠٧ ﺎﻀﻣﺮﯾ( ٠٫٤٣)ض وأﻣﺮا ،٪ ﺪﻣﻲﻘاﻟﺘ ﻓﻲ ٤٤
ﺎﻀﻣﺮﯾ( ٨٫٨٪ )ضواﻟﻤﺮ ﻓﻲاﻟ ﺮﻘﻤﺴﺘ ١٧ ﺎﻀﻣﺮﯾ( ٪٤٫٣ .) ﺑﯿﻦ وﻣﻦ اﻟﻤﺮﺿﻰ
ﻟﻠﺪراﺳﺔ اﻟﺨﺎﺿﻌﯿﻦ ٩٩ ١٨٫٩)٪ ( ﻟﺪﯾﮭﻢ ﻧﺘﻜﺎﺳﻻا وﺔ ) ١٠٠ ٢٪٠٫٠ ( ﺣﺘﻔﮭﻢ ﻮاﻘﻟ .
ﺎتـﺎﺟـاﻻﺳﺘﻨﺘ
• ﻛﺎن اﻟﺪراﺳﺔ، ﺬهھ ﻓﻲ٩٣٣ ﺎﻀﻣﺮﯾ) ٪٨٫٧٦( اﻟﻌﺪواﻧﻲ عاﻟﻨﻮ ﻣﻦ ورامﻸﻟ
ھﺪﺟﯿﻜﻦ اﻟﻐﯿﺮ اﻟﻠﯿﻤﻔﺎوﯾﺔ ﻛﺎن ﺣﯿﻦ ﻓﻲ ، ١٢١ ﺎﻀﻣﺮﯾ) ٢٫٤٢٪ ( عاﻟﻨﻮ ﻣﻦ
واﻟﻤﺘﺨﺎزل٠٤ ﺎﻀﻣﺮﯾ) ٪٠٫٨( عاﻟﻨﻮ ﻣﻦ ﻟﻠﻐﺎﯾﺔاﻟﻌﺪواﻧﻲ .
• ﺖﻤﻨﻀوﺗ ﻟﻠﺪراﺳﺔ اﻟﺨﺎﺿﻌﯿﻦ اﻟﻤﺮﺿﻰ ﻓﻲ جاﻟﻌﻼ اﺳﺘﺠﺎﺑﺔﻞ ﻛﺎﻣ ءﺷﻔﺎ ﻓﻲ ٢٩٦
ﺎﻀﻣﺮﯾ)٪٨٫٣٥ (،ءﺷﻔﺎ ﺟﺰﺋﻲ ١ﻓﻲ٠٧ ﺎﻀﻣﺮﯾ) ٪٠٫٤٣ ( اﻟﺘﺪرﯾﺠﻲ ضوأﻣﺮا ،
ﻓﻲ٤٤ ﺎﻀﻣﺮﯾ) ٪٨٫٨( ضواﻟﻤﺮ اﻟ ﻓﻲ ﺮﻘ١ﻤﺴﺘ ٧ ﺎﻀﻣﺮﯾ) ٪٤٫٣ (.
• و ﻟﻠﺪراﺳﺔ، اﻟﺨﺎﺿﻌﯿﻦ اﻟﻤﺮﺿﻰ ﺑﯿﻦ وﻣﻦ٩٩ )١٪٨٫٩( ﻧﺘﻜﺎﺳﻻا ﻟﺪﯾﮭﻢﮫ و ١٠٠
)٢٪٠٫٠( ﺗﻮﻓﻮا .