Non-Hodgkin Lymphoma in Clinically Difficult Situations

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1 Winship Cancer Institute of Emory University Non-Hodgkin Lymphoma in Clinically Difficult Situations James Armitage, MD Professor, Department of Internal Medicine Joe Shapiro Distinguished Chair of Oncology University of Nebraska Medical Center

2 Lymphoma In Pregnancy Diagnosis Still requires an adequate biopsy Staging Avoid CT and PET/CT Therapy Different issues in 1 st vs. 2 nd and 3 rd trimesters 2

3 Lancet 2012; 379: 580 3

4 Joe Connors 4

5 Maternal And Fetal Complications Based On Lymphoma Type And Therapy (n = 72) JCO 2013; 31:4132 5

6 Evens A M et al. JCO 2013;31: Survival - DLBCL

7 Survival - HL Evens A M et al. JCO 2013;31:

8 Q1. The safest treatment for a four month pregnant 23 year old with stage IIA classical Hodgkin s disease would be? A. ABVD B. Stanford V C. Radiotherapy D. BEACOPP E. ChlVPP

9 A. ABVD B. Stanford V C. Radiotherapy D. BEACOPP E. ChlVPP

10 Relative Risk of Lymphoma Treatments During Pregnancy (based on limited data) Highest Lowest XRT, methotrexate, procarbazine Alkylating agents, antimetabolites ABVD, CHOP, rituximab (?)

11 Q2. A 58-year-old man with recently diagnosed diffuse large B-cell lymphoma was referred. He complains of drenching night sweats and also has a history of coronary artery disease and congestive heart failure with a recent ejection fraction of 35%. Staging evaluation showed an elevated LDH and disease above and below the diaphragm but no extra nodal disease. 11

12 Based on recent data, the best approach would be? 1. CVP-R 2. CHOP-R 3. COPP-R 4. CVP plus etoposide plus R 12

13 Regimens For Patients With Congestive Heart Failure Delete doxorubicin and add: mitoxantrone liposomal doxorubicin etoposide procarbazine 13

14 CHOP-R vs CEOP-R In Patients With DLBCL (Vancouver) Patients with a contra-indication to anthracycline (88% cardiac, 9% previous anthracycline) received etoposide 50 mg/m 2 D1 and 100 mg/m 2 D2,3 CHOP-R CEOP-R Patients 162 (matched controls) 81 5 Year TTP 62% 57% (p=ns) 5 Year OS 64% 49% (p=.02) ASH Abstract #408, Blood 2009;114:170 14

15 1. CVP-R 2. CHOP-R 3. COPP-R 4. CVP plus etoposide plus R 15

16 ALCL And Breast Implants 16

17 Primary Breast Anaplastic Large Cell Lymphoma In Women With Breast Implants 1 st report in 1997, although cases as early as 1994 have been found Mostly silicone filled/coated Incidence is low (i.e. 11 cases in Holland in 17 years) However, when a breast lymphoma develops in a patient with an implant, the odds ratio for ALCL was 18 1 JAMA 2008;300:2030

18 Clinical Characteristics (15 patients) Age years (median 41) Unilateral 81% Usual presentation is pain and swelling Sites of involvement: Local - 58% Regional nodes - 16% >90% ALK negative Distant mets - 26% JAMA 2008;300:2030

19 Treatment For ALCL Associated With A Breast Implant Remove prosthesis and fibrous capsule Surgery alone vs radiotherapy vs chemotherapy +/- radiotherapy Reported 5 year OS 80-90% Oncologist 2013;18:301

20 Follicular Lymphoma In Situ Partial colonization of follicles by neoplastic cells in a patient with no overt follicular or other lymphoma The same concept has been applied to mantle cell lymphoma

21 Follicular Lymphoma In Situ A distinction has been made between this and partial involvement by follicular lymphoma

22 Diagnostic features of FLIS and PFL FLIS Architecture intact Follicle size normal Involved follicles widely scattered Intact cuff with sharp edge to GC Very strong expression of BCL2 and CD10 Almost pure centrocytes Atypical cells confined to GC Jegalian, Blood 2011;118:2976 Altered architecture PFL Follicle size often expanded Involved follicles grouped together in LN Blurred edge to GC and attenuated cuff BCL2 and CD10 more variable in intensity Centrocytes with few centroblasts Atypical cells (CD10 + /BCL2 + B cells) may be found outside the GC

23 Clinical Results In 21 Cases (NCI) Age years (median 52) Female 67% Developed follicular lymphoma 5% Blood 2011;118:2976

24 Management Approach For In Situ Follicular Lymphoma Stage as for overt FL with appropriate biopsies Watch and wait, even with positive flow on peripheral blood Careful follow-up Carbone, Blood 2011;117:39545

25 Mediastinal Gray (or Grey) Zone Lymphoma Not composite mediastinal DLBCL and HL CD 20 (usually), CD 30 and CD 15 positive CD10 and ALK negative Male predominance Usually age yrs Joe Connors

26 Mediastinal Gray Zone Lymphoma PMBCL MGZL NSHL Median age Female 55-70% <50% ~50% Local/regional 70% 90% 50% LDH ~70% ~70% ~20% Extra nodal disease ~60% ~35% ~30% Pleural effusion ~50% ~20% ~10% Joe Connors

27 Comparative Outcomes of Primary Mediastinal B-Cell and Mediastinal Grey Zone Lymphomas Treated with Dose-adjusted EPOCH-R PFS OS Dunlevy, Blood 2009;114 (Abstract #106)

28 Conclusions Mediastinal Gray Zone Lymphoma It appears to be a distinct entity More often localized than PMBCL Most patients will require radiotherapy for cure

29 A 52 year old man is sent to you because of a scalp nodule that was found to be a cutaneous diffuse large B- cell lymphoma on excisional biopsy. The patient was asymptomatic with a normal physical examination. CBC, serum LDH, CT scan of the chest, abdomen and pelvis, and PET scan were all normal after the surgery.

30 Q3. Which would be the best treatment for the completely resected cutaneous diffuse large B-cell lymphoma presenting in the scalp? A. CHOP plus rituximab for 6 cycles B. CHOP plus rituximab for 3 cycles followed by involved field radiotherapy C. 4 weekly doses of rituximab followed by 2 years of maintenance therapy D. Involved field radiotherapy

31 Cutaneous B-cell Lymphomas MALT Primary follicle center (indolent DLBCL) Large B-cell lymphoma leg type (aggressive)

32 A. CHOP plus rituximab for 6 cycles B. CHOP plus rituximab for 3 cycles followed by involved field radiotherapy C. 4 weekly doses of rituximab followed by 2 years of maintenance therapy D. Involved field radiotherapy

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