Hodgkin Lymphoma - Diagnosis to Management

Presentation is about Hodgkin lymphoma, its incidence and epidemiology, diagnosis, molecular and immunophenotype, work up, staging, treatment and follow up

1. Lymphoma-An Introduction & Hodgkin Lymphoma Dr. Subhash Thakur Sr.Lecturer, CMC, Bharatpur, Nepal MD (PGIMER, Chandigarh) 06 th May 2021

2. Content Introduction to Lymphoma Classification Immunophenotyping evaluation Cytogenetic and molecular evaluation Hodgkin Lymphoma Incidence/Epidemiology Diagnosis Staging and risk assessment Treatment A. Classical Limited Stage disease Intermediate Stage disease Relapsed disease B. NLPHL Stage IA without risk factors Other Stages Relapsed NLPHL Response Evaluation Prognosis Follow up, Long term implications and survivorship

3. Lymphoma Clonal neoplasm Expansion of abnormal lymphoid cells that may develop in any organ but commonly involve lymph nodes. Introduction Heterogeneous group of neoplasm with diverse clinical presentation, prognosis and response to therapy

4. Classification: WHO Official and most correct guideline for diagnosis of lymphoid neoplasm Classifies according to type of cell from which they are derived (B Cell, T Cell or NK Cells) Findings determined by morphology, IHC, Clinical, Cytogenetic and/or molecular features

5. Diagnosis: Biopsy Procedure Fresh and unfixed Diagnosis is determined not only by cytological features but also on architectural pattern , So large specimen is preferred ( Excisional Biopsy )

6. Immunophenotype Evaluation Lineage of Lymphoma Cells can not be determined by morphology alone Evaluated by IHC or flow cytometry B-Cell PAX5, CD19, CD79a, CD20 T-Cell CD-2, CD5, CD7 NK Cell CD3, CD5, CD2, CD7, CD16/56

7. Mature B-cell Lymphoma Diffuse large B Cell Lymphoma (DLBCL) Follicular Lymphoma Small B Cell Lymphoma Mantle Cell Lymphoma Marginal zone Lymphoma Burkitt Lymphoma Lymphoplasmacytic Lymphoma

8. Hodgkin Lymphoma Classical NLPHL CD 30 + - CD 15 + - CD 20 +/- + CD 45 - 45

9. Cytogenetic and Molecular Evaluation When morphologic and Immunophenotype analysis is inconclusive or non-diagnostic Molecular Tests: Analysis for rearrangements of the variable region of Ig or T-Cell receptor (TCR) genes Mutation of specific genes

10. Hodgkin Lymphoma Hodgkin Lymphoma Clinical Features Incidence/Epidemiology Diagnosis Staging and risk assessment Treatment A. Classical Limited Stage disease Intermediate Stage disease Relapsed disease B. NLPHL Stage IA without risk factors Other Stages Relapsed NLPHL Response Evaluation Prognosis Follow up, Long term implications and survivorship

11. Clinical Features Painless swelling of lymph nodes in your neck, armpits or groin Persistent fatigue Severe itching Increased sensitivity to the effects of alcohol or pain in your lymph nodes after drinking alcohol

12. B-Symptoms : microscopic spread of disease around the body Fever Drenching Night Sweat Unexplained weight loss (>10% over 6 months)

13. Incidence and Epidemiology Incidence in EU: 2.3 Mortality: 0.4 cases/100000/year Young adult age: 20-40 years most commonly affected Slightly Men > Women Classical HL: 95% NLPHL: 5%

14. Diagnosis Excisional Biopsy According to WHO classification cHL (Classical HL): Reed Sternberg Cell NLPHL: detection of Lymphocyte predominant Cells IHC Classical NLPHL CD 30 + - CD 15 + - CD 20 +/- + CD 45 - 45

15. Hodgkin Lymphoma: classification Classical HL Nodular Sclerosing Lymphocyte Rich Lymphocyte Deficient Mixed Cellularity Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

16. Nodular Sclerosing Common Type, 60 -80 % Women>Men, <50 years Mediastinum Good Prognosis Lymph Nodes: Classical RS cells Lacunar RS Cells

17. Lymphocyte Rich 5 % of HL Cases Rich in small Lymphocytes Small number of classic RS cells

18. Lymphocyte Depletion Rarest and aggressive Older or HIV patients Presents in Stage III/IV Poor Prognosis

19. Mixed Cellularity 15 -30 % of HL cases Usually presents in stage III/IV Poor prognosis

20. Work Up (Investigations Full Blood Count Blood Chemistry analysis: ESR, CRP, ALP, LDH, Liver Enzymes and Albumin Screening for HBV, HCV, HIV

21. Imaging Chest X-ray CECT-Neck, Chest and Abdomen PET-CT, if available If PET not available, Bone marrow Biopsy is must

22. Staging Ann Arbor Staging

23. Risk Stratification

24. Pre-Treatment Examinations ECG Echocardiography Pulmonary Function Tests Reproductive counselling for young patients Serum Pregnancy test in reproductive age group female

25. Treatment – Classical HL A. Limited Stage Disease

26. A. Limited Stage Disease Combined modality treatment consisting of brief Chemotherapy followed by Radiotherapy – Superior Tumour control in comparison to RT alone 2- 3 Cycles of ABVD followed by conventionally fractionated RT

27. Intermediate Stage Disease

28. Intermediate Stage Disease Four Cycles of ABVD followed by conventionally Fractionated RT (30 Gy ) Elderly patients, age > 60 years, Bleomycin should be discontinued after 2 nd Cycle due to Bleomycin induced lung toxicity

29. Advanced Stage Disease Usually treated with Chemotherapy alone Additional RT is confined to patients with residual disease after Chemotherpy

30. Advanced Stage Disease Patients < 60 years are usually treated with either ABVD (six Cycles) or BEACOPPescalated ( 4 – 6 Cycles) optionally followed by localized RT Elderly and Patients at increased risk of Lung toxicity: Bleomycin omitted after 2 nd Cycle

31. Relapsed Disease High Dose Chemotherapy followed by Autologous Stem Cell Transplant (ASCT) Consolidative Treatment with Brentuximab: improved tumour control in patients with at least one of the following feature: Primary disease progression Early disease recurrence <12 months after the end of 1 st line treatment and Extra nodal disease at the time of relapse

32. Disease Recurrence after HDCT followed by ASCT and Brentuximab therapy Anti PD 1 antibodies: Nivolumab , Pembrolizumab approved by FDA In Patients with multiple relapses without further options: Gemcitabine based palliative ChT

33. Treatment of B. NLPHL Stage IA without Risk Factors: Involved Site RT @ 30 Gy alone Other Stages : R-CHOP Rituximab Cyclophosphamide Adriamycin ( Hydroxy -Adriamycin) Oncovin (Vincristine) Prednisolone

34. Relapsed NLPHL Renewed biopsy should be obtained in patients of suspected NLPHL relapse Transformation into aggressive NHL must be ruled out Localized NLPHL: Anti CD20 antibodies (Rituximab or Ofatumumab ) given as single agent Disseminated disease at relapse: aggressive Chemotherapy combined with Anti CD 20 antibody Due to lack of CD30 ab in NLPHL: Brentuximab has no role

35. Response Evaluation If PET is not available then CECT-Neck, chest and Abdomen

36. Follow Up History, Physical Examination and Lab analysis: every 3 months for first 6 month, every 6 months until 4 th year, Once a year thereafter TFT once a year if neck had been irradiated Young Female: mammogram annual after 8-10 year of RT exposure and patients who were < 30 years at time of RT exposure, Breast MRI should be done too.

37. NHL (Non Hodgkin Lymphoma) Some other Class Few important points Chemotherapy and Radiotherapy side effects

38. Thank You !