1 / 65

NHL Board Review

NHL Board Review. Brad Kahl, MD 1/20/04. NHL: Outline. Epidemiology Classification Prognostic Factors Treatment Principles Disease by disease breakdown. NHL: Epidemiology. Most common hematologic malignancy 54,000 new cases annually 6 th leading cause of cancer death (women)

honey
Télécharger la présentation

NHL Board Review

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. NHL Board Review Brad Kahl, MD 1/20/04

  2. NHL: Outline • Epidemiology • Classification • Prognostic Factors • Treatment Principles • Disease by disease breakdown

  3. NHL: Epidemiology • Most common hematologic malignancy • 54,000 new cases annually • 6th leading cause of cancer death (women) • 5th in men • incidence rising • overall incidence up by 73% since 1973 • “epidemic” • 2nd most rapidly rising malignancy

  4. 32% Breast 12% Lung & bronchus 11% Colon & rectum 6% Uterine corpus 4% Ovary 4% Non-Hodgkin’s lymphoma 3% Melanoma of skin 3% Thyroid 2% Pancreas 2% Urinary bladder 20% All other sites Estimated New Cancer Cases*:10 Leading Sites, by Sex, United States, 2003 Prostate 33% Lung & bronchus 14% Colon & rectum 11% Urinary bladder 6% Melanoma of skin 4% Non-Hodgkin’s 4% lymphoma Kidney 3% Oral cavity 3% Leukemia 3% Pancreas 2% All other sites 17% *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Jemal et al. CA Cancer J Clin. 2003;53:5-26.

  5. Incidence of NHL Is Increasing,Especially in the Elderly (60 Years) SEER NHL incidence by age, 1975–1977 and 1998–2000 (male, all races) 140 120 1998–2000 1975–1977 100 80 No. per100,000 60 40 20 0 5 85 5–9 20–24 45–49 10–14 15–19 25–29 30–34 40–44 65–69 70–74 35–39 50–54 55–59 60–64 75–79 80–84 Age at diagnosis (years) Ries et al (eds). SEER Cancer Statistics Review, 1975-2000. National Cancer Institute. Bethesda, Md, http://seer.cancer.gov/csr/1975_2000, 2003.

  6. NHL: Epidemiology • Why the increase? • Increase noted mostly in farming states • MN #1, WI #7 NHL incidence • possible role of herbicides, insecticides, etc. • Other environmental factors • hair dye-very weak association • radiation-no association

  7. NHL: Epidemiology • Other risk factors • immunodeficiency states • AIDS, post-transplant, genetic • Chronic immune stimulation/activation • autoimmune diseases • Sjogrens • Sprue • infections • H. pylori, EBV, HHV-8

  8. Revised European-American Lymphoma (REAL) Classification: B-Cell Neoplasms • Indolent • CLL/SLL • Lymphoplasmacytic/IMC/WM • HCL • Splenic marginal zone lymphoma • Marginal zone lymphoma • Extranodal (MALT) • Nodal • Follicle center lymphoma, follicular, grade I-II • Aggressive • PLL • Plasmacytoma/Multiple myeloma • MCL • DLCL • Primary mediastinal large B-cell lymphoma • Follicle center lymphoma, follicular, grade III • Very Aggressive • Precursor B-lymphoblastic lymphoma/Leukemia • Burkitt’s lymphoma/ B-cell acute leukemia • Burkitt’s-like • Plasma cell leukemia Hiddemann. Blood. 1996;88:4085.

  9. NHL: Approach to the Patient • Staging evaluation • History and PE • Routine blood work • CBC, diff, plts, electrolytes, BUN, Cr, LFT’s, uric acid, LDH, B2M, HIV • CT scans chest/abd/pelvis • Bone marrow evaluation • Other studies as indicated (lumbar puncture, MRI, PET, etc…)

  10. Modified Ann Arbor Staging of NHL Stage I Involvement of a single lymph node region Stage II Involvement of  2 lymph node regions on the same side of the diaphragm Stage III Involvement of lymph node regions on both sides of the diaphragm Stage IV Multifocal involvement of  1 extralymphatic sites ± associated lymph nodes or isolated extralymphatic organ involvement with distant nodal involvement Cancer. 1982;49:2112.

  11. Modified Ann Arbor Staging of NHL • “E” designation for extranodal disease • B symptoms • recurrent drenching night sweats during previous month • unexplained, persistent, or recurrent fever with temps above 38 C during the previous month • unexplained weight loss of more than 10% of the body weight during the previous 6 months • Criteria for bulk • 10 cm nodal mass • mediastinal mass > 1/3 thorax diameter

  12. International Prognostic Index (IPI) Patients of all ages Risk factors Age > 60 years Performance status (PS) 2-4 Lactate dehydrogenase (LDH) levelElevated Extranodal involvement> 1 site Stage (Ann Arbor)III–IV Patients  60 years (age-adjusted) PS 2-4 LDHElevated StageIII–IV Shipp. N Engl J Med. 1993;329:987.

  13. IPI Risk Strata Risk Factors All ages Low (L) 0-1 Low-intermediate (LI) 2 High-intermediate (HI) 3 High (H) 4-5 Age-adjusted L 0 LI 1 HI 2 H 3 Risk Group Shipp. Blood. 1994;83:1165.

  14. IPI: Overall Survival by Risk Strata 100 75 Patients (%) 50 L LI HI 25 H 0 0 2 4 6 8 10 Year Adapted from Shipp. N Engl J Med. 1993;329:987.

  15. Age-Adjusted IPI: Overall Survival by Risk Strata 100 L 75 LI Patients (%) 50 HI H 25 0 0 2 4 6 8 10 Year Adapted from Shipp. N Engl J Med. 1993;329:987.

  16. Follicular Lymphoma (FL) : Overall Survival 100 80 IPI 0/1 60 Overall Survival (%) IPI 2/3 40 20 P < 0.001 IPI 4/5 0 0 1 2 3 4 5 6 7 8 Year Adapted from Armitage. J Clin Oncol. 1998;16:2780.

  17. NHL: Approach to the Patient • Approach dictated mainly by histology • reliable hematopathology crucial • Approach also influenced by: • stage • prognostic factors • co-morbidities

  18. Stage I-II Disease “Watchful waiting” Radiation Stage III-IV Disease “Watchful waiting” Purine analogs Alkylating agents Combination chemotherapy MoAbs (conjugated and unconjugated) Chemotherapy + MoAbs Intensive chemotherapy + autologous/allogeneic bone marrow (BM) or peripheral blood (PB) transplantation Treatment Strategies for Indolent NHL

  19. Indolent NHL: chlorambucil vs W&W

  20. Indolent NHL: What are reasonable first line therapies?

  21. NHL: Approach to the Patient • Indolent NHL: guiding treatment principle • early treatment does not prolong overall survival • When to treat? • constitutional symptoms • compromise of a vital organ by compression or infiltration, particularly the bone marrow • bulky adenopathy • rapid progression • evidence of transformation

  22. NHL: Approach to the Patient • Aggressive NHL: treatment approach • Stage I-II: combined modality therapy • R-CHOP chemotherapy x 3 + IF radiotherapy • Consider more chemo if bulky, high LDH, stage II • Stage III-IV (also bulky stage II) • R-CHOP chemotherapy x 6-8 cycles • Great lesson in clinical trials

  23. National High Priority Lymphoma Study: Progression-Free Survival 100 CHOP m-BACOD ProMACE-CytaBOM 80 MACOP-B 60 Patients (%) 40 20 0 0 1 2 3 4 5 6 Years After Randomization Adapted from Fisher. N Engl J Med. 1993;328:1002.

  24. Diffuse Large B-Cell Lymphoma (DLCL): Overall Survival 100 80 IPI 0-1 60 Patients (%) 40 IPI 2-3 IPI 4-5 20 P < 0.001 0 0 1 2 3 4 5 6 7 8 Year Adapted from Armitage. J Clin Oncol. 1998;16:2780.

  25. NHL: Approach to the Patient • Role for Stem Cell Transplantation (auto) • Aggressive NHL • clear benefit when used for aggressive NHL in first relapse in appropriately selected patients • 1/3 of these patients can be cured by SCT • Indolent NHL • no convincing evidence that patients are cured • CUP trial suggests survival advantage for ASCT

  26. NHL: Elderly • Indolent histology • usual principles apply • Aggressive histologies • trials have consistently shown that prophylactic dose reductions/delays/omissions result in inferior outcomes • PS predicts outcome rather than chronological age • routine use of growth factors reduces FN and infections, does not improve survival. NCCN guidelines recommends routine use in patients over age 70 treated with CHOP. • R-CHOP superior to CHOP in GELA trial for DLBCL

  27. DLBCL Actually a heterogenous group • 3 subtypes by microarray • Germinal center B cell like • Activated peripheral blood B cell like • Type 3

  28. DNA Microarray Alizadah et al, Nature,2000:403;503 • examined gene expression profiles in DLCL tumor samples • compared to profiles of non-malignant B cells • noted emergence of patterns

  29. DNA Microarray Alizadah et al, Nature,2000:403;503 • Reviewed clinical outcome data • Gene expression profiles had prognostic value • Added to IPI

  30. DNA Microarray Rosenwald et al. NEJM 2002:346;1937

  31. DNA Microarray Rosenwald et al. NEJM 2002:346;1937

  32. Biologic Factors Bcl-2 Predictive Power in DLBCL • Hermine et al. Blood 87:265, 1996 DFS, OS • Kramer et al. JCO 14:2131, 1996 DFS • Hill et al. Blood 88:1046, 1996 DFS • Gascoyne et al. Blood 90:244, 1997 DFS, OS • Kramer et al. Blood 92:3152, 1998 DFS, OS

  33. BCL-2 expression vs survivalR. Gascoyne et al, Blood 90:244, 1997

  34. Biology Summary • Microarray studies indicate 3 distinct subtypes of DLBCL based upon gene expression profile • Challenge is to better understand the intracellular derangements unique to each subtype so that new targeted therapies can be developed • Develop easily applicable lab techniques to distinguish the different biological entities (morphology does not do it)

  35. Follicular Center Cell NHL • 3 Grades • Grade 1: 0-5 centoblasts/HPF • Grade 2: 6-15 centroblasts/HPF • Grade 3: > 15 centroblasts/HPF • 3a: no sheets of large cells • 3b: sheets of large cells • Characterized by t(14;18) • Overexpression of bcl-2 • Flow cytometry: CD10+

  36. MALT • Lymphoma arises in tissue normally devoid of lymphoid tissue • Stomach, lungs, orbit, skin, breast, salivary glands • Gastric MALT unique due to high association with H. pylori • Often regresses after H. pylori eradication therapy • t(11;18) predicts non response to H pylori therapy

  37. T-Cell NHL • Will lack B cell antigens • CD20, sIg • Should have T cell markers • CD3+, CD4+ or CD8+ • Harder to tell if clonal • Can’t do simple kappa/lamda • Can look for clonal T cell receptor gene rearrangements with molecular studies

More Related