Hodgkins lymphoma kiran

Hodgkins lymphoma kiran

1. HODGKINS LYMPHOMA Dr Kiran

2. EPIDEMIOLOGY AND RISK FACTORS Incidence  less than 3 per 100,000. Accounts for 0.56% of all cancers diagnosed. Male predominance (1.2:1). Rare in children <10 years of age. Median age at diagnosis  26 years.

3. Incidence has a bimodal peak as a function of age. Early peak  from ages 25 to 30 years. Second peak  from age 75 to 80 years. Peak in older adults  “contaminated” by cases that were actually anaplastic large-cell or diffuse large-cell lymphoma.

4. Weiss et al. : Relation between HD and EBV infection. EBV genome in the DNA of Reed-Sternberg (RS) cells. Mueller et al . : Elevated levels of IgG and IgA against the EBV capsid antigen. Antibody against EBV nuclear antigen. Antigen D in the serum 3 to 156 months before the diagnosis of Hodgkins lymphoma.

5. Risk for development of Hodgkin lymphoma  2.55 times higher among individuals who have a history of infectious mononucleosis . Several series demonstrated an association between EBV infection and mixed- cellularity Hodgkin lymphoma, especially in children in developing countries. Ultimate relationship between EBV infection and development of Hodgkin lymphoma remains undefined .

6. NATURAL HISTORY AND CLINICAL PRESENTATION Present with painless lymphadenopathy  90% of patients contiguous sites of involvement. Systemic symptoms such as : Unexplained fevers : classic waxing-and-waning Systemic ‘B ’ Pel-Ebstein pattern . Drenching night sweats . Symptoms Significant weight loss . Generalized pruritus. Fatigue. Alcohol-induced pain in tissues involved by Hodgkin lymphoma. Diagnosed after detection of a mediastinal mass on a routine chest radiograph.

7. Organ involvement by Hodgkin lymphoma  secondary to extension from adjacent lymph nodes. Eg : Spread from enlarged mediastinal or pulmonary hilar nodes: Directly into the pulmonary parenchyma or Hematogenous such as nodular disease in the liver or multiple bony sites. Involvement of the bones  cause blastic changes in the vertebrae (creating the classic “ ivory vertebra ” on plain radiographs), pelvis, sternum, or ribs.

8. Nearly all patients with hepatic or bone marrow involvement by Hodgkin lymphoma  extensive involvement of the spleen. Rarely involves the gut-associated lymphoid tissues such as Waldeyer ring and Peyer patches. Rarely involves the upper aerodigestive tract, central nervous system, and skin .

9. Children  good prognosis compared with adults. Older adults (>60 years)  worse prognosis  secondary to intercurrent illness or the ability to tolerate standard therapies, especially bleomycin, anthracyclines and extended-field irradiation.

10. DIAGNOSTIC WORK UP A. History. B. Physical examination. C. Biopsy.

11. D. Hematologic evaluation : Complete blood count , differential and platelet : Anemia , leukopenia , lymphopenia , or thrombocytosis . Paraneoplastic effect but it may be indicative of bone marrow involvement. Anemia , lymphopenia , and hypoalbuminemia  adverse prognostic factors , especially for patients with advanced disease (stage III–IV).

12. Serum alkaline phosphatase  nonspecific marker of tumor activity or hepatic, bone marrow, or bone disease. Erythrocyte sedimentation rate (ESR)  correlate with response to treatment and subsequent disease activity and is a prognostic factor for patients with limited disease (stage I–II). Other useful markers  lactate dehydrogenase and β 2 - microglobulin levels.

13. E. Radiographic evaluation : PA and lateral chest radiographs : Mediastinal adenopathy  quantitated by a measurement of the maximum width of the mediastinal mass divided by the maximum intrathoracic diameter (near the level of the diaphragm) on a standing PA chest radiograph. If ratio exceeds 1:3  disease is defined as bulky and this affects assignment to many clinical trials. Other definitions of bulky mediastinal adenopathy : A mass >10 cm. Ratio of mediastinal mass to the chest diameter at T5-6 exceeding 0.35 (EORTC clinical trials).

14. Contrast-enhanced (diagnostic) computed tomographic (CT) scans of the chest, abdomen, and pelvis  reveal adenopathy or organ involvement. Splenomegaly or hepatomegaly alone cannot be interpreted to represent involvement by Hodgkin lymphoma  enlarged spleens often are not involved at the time of splenectomy . Presence of focal nodules  indicative of involvement.

15. Positron emission tomography (PET) : using 2-fluoro-2-deoxy-D-glucose (FDG), especially with fused CT images (PET-CT scan)  an important component of initial staging in Hodgkin lymphoma. FDG-PET  more sensitive than CT for detecting disease  r eveal unsuspected bone or bone marrow disease. Essential study for response assessment  useful for the evaluation of residual masses detected by CT scanning. Useful prognostic indicator when repeated after just a portion of chemotherapy has been administered.

16. Magnetic resonance imaging : alternative to chest or abdominal-pelvic CT scanning for initial staging. For staging evaluation of women during pregnancy. Bone marrow biopsy : posterior iliac crest bone marrow  selected patients. Bone marrow biopsy rarely positive . Not required  Stages I–IIA disease. Should be done if : CBC is abnormal. Stages III and IV disease. B symptoms . Overall incidence of bone marrow involvement in Hodgkin lymphoma  ~5%.

17. STAGING Ann Arbor staging system  used since 1971. Includes designation of a clinical stage, based on: Results of the initial biopsy and clinical staging studies and a pathologic stage . Any subsequent biopsies, including bone marrow biopsy and those obtained at staging laparotomy .

18. THE ANN ARBOR STAGING CLASSIFICATION FOR HODGKIN’S DISEASE

19. PATHOLOGIC CLASSIFICATION Neoplastic cell of classic Hodgkin lymphoma  Reed–Sternberg cell. Binucleate . A prominent centrally located nucleolus in each nucleus. A well-demarcated nuclear membrane. Eosinophilic cytoplasm with a perinuclear halo. Account for <1% of the cells in a lymph node involved by Hodgkin lymphoma. Majority are lymphoid cells, eosinophils , plasma cells, and other normal cells.

20. REED STERNBERG CELLS

21. 5 histologic subtypes of Hodgkin lymphoma as defined by the WHO modification of the Lukes and Butler system. Nodular lymphocyte-predominant Hodgkin lymphoma. Four subtypes of classic Hodgkin lymphoma: Nodular sclerosis. Mixed cellularity . Lymphocyte-rich. Lymphocyte-depleted.

22. 1. NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA (NLPHD) Accounts for <5% of HL. Characterized by the presence of an RS cell variant known as L & H cell or popcorn cell . Express Bcell markers  CD20+, CD79a+, CD45+ and J chain+. CD15 - ve and CD30 - ve . Usually presents in middle-aged males. Present with early-stage disease. Localized peripheral lymph node involvement (cervical, axillary , and inguinal regions). Systemic symptoms  uncommon (<10%).

23. Natural history  most favorable . Occasional patients demonstrate a pattern of late relapse but good survival  similar to that observed in the follicular (B-cell) lymphoma. 14% of patients with nLPHD may transform to an aggressive B-cell lymphoma. A reactive process termed progressive transformation of germinal centers may be observed in conjunction with nLPHD .

24. CLASSIC HODGKINS LYMPHOMA 4 histologic subtypes. Classical HL the RS cells are Positive  CD30 and CD15. Negative  CD45 and the J chain .

25. 2. NODULAR SCLEROSIS CLASSICAL HODGKIN LYMPHOMA (NSHD) Most common histologic subtype  accounting for 65–70% of cases. Characterized by : Nodular growth pattern. Presence of collagen bands . RS cell variant known as the lacunar cell .

26. Only subtype without a male predominance  male : female ratio approximately 1:1. Clinical presentation  mediastinal involvement, and 1/3rd of patients have B symptoms. Natural history  L ess favorable than that of nLPHD .

27. 3. MIXED-CELLULARITY CLASSIC HODGKIN LYMPHOMA (MCHD) Represents 10–15% of cases Present with advanced disease . Tendency to involve spleen, bone marrow and a lesser tendency for mediastinal involvement. Slightly older than those with NSHD or nLPHD . Natural history  L ess favorable than that of NSHD .

28. 4. LYMPHOCYTE-RICH CLASSIC HODGKIN LYMPHOMA (LRHD) Represents ~5% of HL. Nodular growth pattern. Clinical characteristics of patients affected by LRHD are similar to those of nLPHD  Early stage . Absence of B symptoms. Excellent prognosis .

29. 5. LYMPHOCYTE-DEPLETED CLASSIC HODGKIN LYMPHOMA (LDHD) Uncommon subtype. Difficult to differentiate from anaplastic large-cell lymphoma. Older patients. Associated with advanced disease and B symptoms. Worst prognosis .

30. PROGNOSTIC FACTORS DEFINITION OF “UNFAVORABLE” STAGE I TO II HODGKIN LYMPHOMA IN RECENT CLINICAL TRIALS

31. INTERNATIONAL PROGNOSTIC SCORE FOR ADVANCED HODGKIN LYMPHOMA FACTOR UNFAVOURABL E COVARIATE Serum albumin <4 g/dl Hemoglobin <10.5 g/dl Sex Male Age > = 4 5yrs Stage IV (Ann Arbor) Leukocyte count >= 15,000/mm 3 Lymphocyte count <600/mm 3 or <89% of white count

32. GENERAL MANAGEMENT

33. CHEMOTHERAPY Initial successful drug combination : MOPP reported by DeVita et al. from the National Cancer Institute in 1970. Nitrogen mustard. Vincristine . Procarbazine and Prednisone Acute toxicities  significant. Late effects of concern  sterility (especially in men) and risk for secondary myelodysplastic syndrome or leukemia . MOPP-like programs  chlorambucil , vinblastine , procarbazine , and prednisone ( ChlVPP )  comparable results with similar drugs and less toxicity

34. ABVD  D oxorubicin Bleomycin Vinblastine Dacarbazine Replaced MOPP. Gold standard of chemotherapy for Hodgkin lymphoma.

35. COMMON DRUG COMBINATIONS

36. COMBINED-MODALITY THERAPY Important considerations : Sequence of therapy . Selection of irradiation fields . Decision to irradiate all involved sites : - only initially “bulky” site or - only sites that have not responded completely to chemotherapy. Prescription of dose. Potential overlapping toxicities.

37. Treatment is almost always initiated with chemotherapy. Advantages of treating all sites of disease at the outset (especially important in stage III or IV)  reducing bulky disease to facilitate subsequent irradiation (especially in the mediastinum ). Irradiation dose used in combined-modality studies in adults ranges from 20 to 36 Gy.

38. Radiation therapy is used in the combined-modality setting  Doses vary depending on the : Prognostic category of patients. Bulk of disease and Type and duration of chemotherapy. The range of doses considered acceptable according to the NCCN guidelines : 20 to 30 Gy for nonbulky and 1.5 to 1.8 Gy 30 to 36 Gy for bulky sites of disease per fraction

39. In the context of combined-modality therapy programs Clinical trials have demonstrated an equivalence of “involved-field” treatment (IFRT) with “extended-field” or “subtotal-lymphoid” irradiation. Involved-field irradiation  adopted as the standard for combined-modality therapy. More recent trials  application of even more restricted fields  “involved-node radiotherapy” (INRT) of “involved-region” or “involved-site” irradiation.

40. RADIATION THERAPY Classic field configurations for the treatment of Hodgkin lymphoma by radiotherapy alone  M antle and inverted-Y.

41. INVOLVED FIELD AND INVOLVED SITE FIELD

42. TREATMENT OF EARLY FAVORABLE DISEASE

43. TREATMENT OF EARLY UNFAVORABLE DISEASE

44. TREATMENT OF ADVANCED-STAGED DISEASE ABVD  6 to 8 cycles  S tandard treatment . Alternative approach of Stanford V being acceptable. BEACOPP  better disease control  in patients with adverse prognosis  increased treatment toxicity.

45. TREATMENT OPTIONS FOR NLPHL

46. TREATMENT OF REFRACTORY AND RELAPSED HL Refractory HL  progression of disease during initial therapy or within 3 months of completion of treatment. Relapsed HL  disease progression after a CR to primary treatment (early relapse is further defined as within 12 months of CR)

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