Lymphoma

 

Epidemiology

•        In 2008, HL was estimated 8,220 new diagnose and 1, 350 deaths in USA

•        An estimated 66,120 new cases of NHL will be diagnosed in 2008 and 19,160 deaths will occur in USA

•        The lymphoma are the most commonly occurring hematologic malignancies in the China

•        There are over 50,000 new cases of NHL and about 5,000 new cases of HL per year in China

 

Relative incidence of Lymphoma (4804 cases in southern China)

Etiology

•       A number of studies have suggested that there appears to be a genetic predisposition for Hodgkin lymphoma

•       The cause of most cases of NHL is unknown, although several genetic diseases, environmental agents, and infectious agents have been associated with the development of lymphoma

 

 

Several factor relative to  prognosis of lymphoma

lPathogenetic subgroup

lStaging

lPrognostic factors

lResponse Assessment

lParticular site

NHL

 

distinct subgroups and staging

IWF
REAL
WHO（2001/2008）Classification of Lymphoma

 

 

 

 

 

Ann Arbor Staging System

I   Involvement of a single lymph node region or a single extralymphatic organ or site (IE)

II  Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of an extralymphatic organ or site (IIE)

III Involvement of lymph node regions on both sides of the diaphragm (III) or localized involvement of an extralymphatic organ or site (IIIE) or spleen (IIIS) or both (IIISE)

IV Diffuse or disseminated involvement of one or more extralymphatic organs with or without associated lymph node involvement. Bone marrow and liver involvement are always stage IV

    Identification of the presence or absence of symptoms should be noted with each stage designation: A, asymptomatic; B, fever, sweats, weight loss greater than 10% of body weight.

PET-CT use in lymphoma staging

High risk or prognostic factors

Suitable study of IPI in Chinese DLBCL

Response Criteria for Malignant Lymphoma

IWG Response Criteria for NHL

PET(–) residual mass in a patient with DLBCL

Revised Response Criteria for Malignant Lymphoma（2007）

Clinical Features and  Treatment

DLBCL

Clinical Features

•        DLBCL was the most common lymphoma in the REAL/WHO classification

•        Patients typically present with a rapidly enlarging symptomatic mass, with B cell symptoms in one third of the cases.

•        Localized (stage I or II) extranodal disease occurs in up to 30%; bone marrow involvement was seen in only 16%.

•        Up to 40% of DLBCLs are extranodal; common sites include the gastrointestinal tract, bone, and CNS

Comparison of CHOP with Three Intensive Chemotherapy Regimens for Advanced NHL

•        Conclusions CHOP remains the best available treatment for patients with advanced-stage intermediate-grade or high-grade non-Hodgkin's lymphoma.

The efficacy of Radiotherapy in DLBCL

Chemo Alone Compared with Chemo+Radio for Localized aggressive NHL

•        Conclusions Three cycles of CHOP followed by involved-field radiotherapy are superior to eight cycles of CHOP alone for the treatment of localized aggressive NHL

Development of Dose-Dense and
Dose-Intense Regimens

Biweekly or 3-weekly CHOP for patients with DLBCL

Biweekly or 3-weekly CHOP ±etoposide for elderly patients with aggressive lymphomas

•        Conclusion: Due to its favorable efficacy and toxicity profile, CHOP-14 should be considered the new standard chemotherapy regimen for patients ages 60 or older with aggressive lymphoma.

The Rituximab Effect

Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients With DLBCL

•60–80y，previously untreated patients, 399

 

Treatment of DLBCL

R-CHOP21, golden standard regimen！

Burkitt‘s Lymphoma

 

Burkitt‘s Lymphoma

•         A highly aggressive B-cell neoplasm, often presenting in extranodal sites or as an acute leukemia, composed of monomorphic, medium-sized cells with basophilic cytoplasm and an extremely high proliferation rate

•         Translocation and deregulation of c-myc on chromosome 8 is a constant feature

•         EBV is found in a high proportion of the cases, particularly in the African-endemic form

•         one of the first malignancies shown to be curable with chemotherapy, and the majority of adult patients should be curable today with aggressive combination chemotherapy regimens

Burkitt‘s Lymphoma

•        High-dose regimens (such as CODOX-M/IVAC) of fairly brief duration are most often used to treat patients

•        These regimens include higher doses of alkylating agents than CHOP and include prophylaxis to the CNS with both intrathecal and high-dose systemic therapy

•        Patients with localized disease are cured in approximately 90% of the cases with these intensive regimens, and cure rates within excess of 50% have been reported in patients with extensive disease

 

Mantle Cell Lymphoma

Clinical Features

•         Accounts for approximately 7% of adult NHLs in the United States and Europe

•         It is a tumor of older adults, with a marked male predominance (75%). The majority (70%) of patients are in stage IV at diagnosis; sites involved include lymph nodes, spleen, Waldeyer's ring, bone marrow (greater than 60%), blood (up to 50%), and extranodal sites, especially the gastrointestinal tract

•         The course is moderately aggressive. The median OS in most historical series is 3 years, with no plateau in the curve, and failure-free survival is approximately 18 months. The blastoid variant is reported in some studies to be more aggressive

 

Mantle Cell Lymphoma

Mantle Cell Lymphoma

•                 Widely accepted as an entity only in the past 15 years

•                 The optimal treatment for these patients is not known.

•                 Approaches reported in these individuals include involved-field radiation and the combination of R-CHOP chemotherapy and involved-field irradiation

R- Hyper-CVAD/R-HD-MA

•        Of 97 assessable patients

•        97% responded and 87% achieved CR or unconfirmed CR.

•        the 3-year PFS and overall survival rates were 64% and 82%

 

Indolent NHL

Indolent NHL

*        Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

*        Lymphoplasmacytic Lymphoma (With or Without Waldenstrom's Macroglobulinemia)

*        Extranodal Marginal Zone B-Cell Lymphoma (B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue)

*        Nodal Marginal Zone B-Cell Lymphoma

*        Splenic Marginal Zone Lymphoma

*        Follicular Lymphoma

 

Clinical Features of Follicular Lymphoma

•         The second most common lymphoma in the United States and western Europe

•         Affects predominantly older adults, with a slight female predominance

•         Most patients have widespread disease at diagnosis, usually predominantly involving lymph nodes, but also spleen, bone marrow, and occasionally peripheral blood or extranodal sites

•         Despite the advanced stage, the clinical course is generally indolent; however, the disease is not usually curable with available treatment. Utilizing the follicular lymphoma IPI, a group of patients with relatively poor survival (50% at 5 years) can be identified

FLIPI

Survival (1795 cases)

 

25y experiences of treatment IV FL in M.D. Anderson Cancer Center

Initial Treatment of Follicular Lymphoma

•            Patients with early stage follicular lymphoma should be considered for treatment with primary RT

•            Many treatment options exist for the majority of patients with newly diagnosed, disseminated follicular lymphoma. Whenever possible, the patients were strongly encourage participation in clinical trials.

•            Observation remains an option for certain asymptomatic patients; however, this approach has no chance at improving survival for these individuals. Monoclonal antibodies, particularly rituximab, have activity as a single agent for patients with nonbulky disease.

Initial Treatment of Follicular Lymphoma

•            For symptomatic patients or those with bulky disease requiring a rapid response, combination chemotherapy regimens including alkylating agents or purine analogs, along with rituximab, are appropriate

•            The role of radioimmunoconjugates (Yttrium , Iodine ), Id vaccination, or more aggressive approaches, including autologous stem cell transplantation (ASCT) as part of initial therapy, remain to be defined.

CVP±R for FL

FLIPI

Long-Term Follow-Up of Gastric MALT Lymphoma After Helicobacter Pylori Eradication

Survival

•        CONCLUSION: Cure of Hp infection results in CCR in most patients. Histologic RD, B-cell monoclonality, and t(11;18) were present in a considerable number of CR patients. A watch-and-wait strategy is justified when close follow-up is guaranteed

Lymphoblastic Leukemia/Lymphoma

Lymphoblastic
 Leukemia/Lymphoma

•       Precursor B- and T-Cell Neoplasms

•       typically composed of small to medium-sized blast cells with scant cytoplasm, moderately condensed to dispersed chromatin and indistinct nucleoli, variably involving bone marrow and blood, thymus, or lymph nodes

Clinical Features

•        there is a mediastinal or other mass and fewer than 25% blasts in the bone marrow and as leukemia if there are greater than 25% bone marrow blasts, with or without a mass

•        Treatment regimen similar with lymphocyte leukemia (BFM, Hyper-CVAD)

 

Adult T-Cell Lymphoma and Leukemia

•         ATL is a peripheral T-cell neoplasm usually composed of highly pleomorphic cells involving lymph nodes and peripheral blood and often skin and extra-nodal sites. ATL is caused by the human retrovirus, human T-cell leukemia virus type 1 (HTLV-1)

•         The treatment of ATL has been unsatisfactory

Peripheral T-Cell Lymphoma, Unspecified

•            comprises a group of predominantly nodal and occasionally extranodal T-cell lymphomas, which do not have consistent immunophenotypic, genetic, or clinical features

•            The median age was in the 70th decade, and 65% of the patients had stage IV disease. Blood eosinophilia, pruritus, and hemophagocytic syndromes may occur; lymph nodes, skin, liver, spleen, and other viscera may be involved. The clinical course is aggressive, and relapses may be more common than in large B-cell lymphoma

Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

•         a rare disorder in the United States and Europe but is more common in Asia

•         Extranodal sites are invariably involved, including nose, palate, upper airway, gastrointestinal tract, and skin. The clinical course is typically aggressive, with relapses in other extranodal sites. Hemophagocytic syndromes may occur.

•         Radiotherapy is the important treatment

Mycosis Fungoides and the Sezary Syndrome

•        MF, the most frequently observed CTCL

•        The clinical features of the disease are variable and may be in the form of patches, plaques, erythroderma, cutaneous tumors, or ulcers. In early patch or plaque stage disease, the clinical features are indistinguishable from those of benign dermatoses, including psoriasis, eczema, large plaque parapsoriasis, or drug eruptions

 

Treatment

•       Skin-directed modalities (radiotherapy) 

•       Topical Chemotherapies

•       Topical Bexarotene Gel (retinoid X receptor)

•       Phototherapy

•       Total Skin Electron-Beam Therapy

•       Histone Deacetylase Inhibitors

 

Particular site

Primary intestinal lymphoma（operation +chemo）

Primary Gastric lymphoma

 

•       DLBCL：Chemo+Radio（operation）

Primary Breast lymphoma

•       Most of DLBCL

•       DLBCL: Chemo + Radio；Contralateral Radio；CNS?

Primary Testicular lymphoma

•       Most of DLBCL

•       Operation + Chemo

•       CNS: High dose MTX

•       Contralateral low dose radiotherapy

Primary CNS lymphoma

•       Most of DLBCL

•       AIDS?

•       High dose MTX+Ara-C+Dexa，intrathecal injection

•       Radiotherapy

•       High dose Chemo supporting SCT

•       Timodar\liposome Ara-C

 

Review focus

•   EBV-Burkitt’s; HTLV-1-ALT; HP-MALT

•   Ann Arbor Staging System

•   IPI

•   FLIPI

•   DLBCL is the most common subtype of NHL. R-CHOP21 is the golden standard regimen for DLBCL.

•   Advances in management of indolent lymphoma

 

Hodgkin Lymphoma

•          The clinical features and responses to treatment of HL differ dramatically from NHL

•          Totally, about 80% patients can be cured at present

 

Clinical Presentation (HL)

•            The most characteristic clinical presentation of HL is enlarged superficial lymph nodes in young adults, with the most frequent locations being cervical/supraclavicular (60% to 80%), high in the neck, or axillary

•            A mediastinal involvement is discovered often by routine staging chest radiography, and even fairly large masses may occur without producing local symptoms

•        Patients may present with abdominal swelling secondary to hepato- or splenomegaly or, rarely, with ascites.

Clinical Presentation (HL)

•            Involvement of the central nervous system or bone marrow is rare

•            Initial symptoms of disease limited to extranodal tissue are much rarer in HL than in NHL.

•            A significant proportion of undiagnosed patients with HL presents systemic symptoms prior to the discovery of enlarged lymph nodes. Typical symptoms are fever, drenching night sweats, and weight loss (so-called B-symptoms, relating to the Ann Arbor classification)

Specific Morphologic Features of Hodgkin Lymphoma

Classification of HL

•       Nodular Lymphocyte Predominance Hodgkin Lymphoma

•       Lymphocyte-Rich Classic Hodgkin Lymphoma

•       Nodular Sclerosis Hodgkin Lymphoma

•       Mixed Cellularity Hodgkin Lymphoma

•       Lymphocyte Depleted Hodgkin Lymphoma

 

Cotswolds staging classification for HL

Prognostic Factors for Early Stages (Stage I-II)

•        Age (45y)

•        Male sex.

•        B symptoms.

•        Large mediastinal mass (LMM).

•        Number of involved nodal regions (>3)

•        Elevated erythrocyte sedimentation rate (ESR).

•        Anemia.

•        Low serum albumin.

 

International Prognostic Factors Project for Advanced Stages

•       Age >45

•       Male

•       Stage IV

•       Serum albumin <4 g/dL

•       Hemoglobin <10.5 g/dL

•       White blood cell count >15,000/mm3

•       Lymphocyte count <600/mm3 or <8% of white blood cell count

IPS

irradiation
for early stage
HL

 

BEACOPP v COPP-ABVD for advanced stage HL

Criterion of Treatment

•        Early stages, favorable: radiation alone (extended field); chemotherapy (2-4 cycles ABVD) plus radiation

•        Early stages, unfavorable: moderate amount of chemotherapy (6 cycles ABVD) plus radiation

•        Advanced stages: extensive chemotherapy (8 cycles BEACOPP) with or without consolidation radiotherapy (usually local).

Response adaption using FDG-PET after two courses of chemotherapy to predict response and prognosis.

High-Dose Chemotherapy Plus Stem Cell Support

•        HDCT as an important component in the management of progressive and relapsed Hodgkin lymphoma. HDCT followed by ASCT has been shown to produce 30% to 70% long-term disease-free survival in selected patients with primary progressive and relapsed disease

•        Although results of HDCT have generally been better than those observed after conventional-dose salvage therapy, the validity of this comparison has been questioned because of the lack of randomized trials

The patients are encouraged to participate in clinical trial!

Review focus

•           Classification of HL

•           Cotswolds staging classification for HL

•           Prognostic Factors for Early Stages

•           IPS

•           Criterion of Treatment in HL