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 Disclosures • Consulting fees from: – GlaxoSmithKline, Genentech, Roche, Seattle Genetics, Spectrum, Ziopharm – Board of Director’s for: Tesaro Bio., Inc. 1
Lymphoma In Pregnancy Diagnosis – Still requires an adequate biopsy Staging – Avoid CT and PET/CT Different issues in 1 st vs. 2 nd and Therapy – 3 rd trimesters 3 Lancet 2012; 379: 580 4 2
Joe Connors 5 Maternal And Fetal Complications Based On Lymphoma Type And Therapy (n = 72) 6 JCO 2013; 31:4132 3
Survival - DLBCL Evens A M et al. JCO 2013;31:4132-4139 Survival - HL Evens A M et al. JCO 2013;31:4132-4139 8 4
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 A. ABVD B. Stanford V C. Radiotherapy D. BEACOPP E. ChlVPP 5
Relative Risk of Lymphoma Treatments During Pregnancy (based on limited data) Highest • XRT, methotrexate, procarbazine • Alkylating agents, antimetabolites • ABVD, CHOP, rituximab (?) Lowest 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. 12 6
Based on recent data, the best approach would be? 1. CVP-R 2. CHOP-R 3. COPP-R 4. CVP plus etoposide plus R 13 Regimens For Patients With Congestive Heart Failure Delete doxorubicin and add: mitoxantrone liposomal doxorubicin etoposide procarbazine 14 7
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) 15 ASH Abstract #408, Blood 2009;114:170 1. CVP-R 2. CHOP-R 3. COPP-R 4. CVP plus etoposide plus R 16 8
ALCL And Breast Implants 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 9
Clinical Characteristics (15 patients) • Age 13-68 years (median 41) • Unilateral 81% • Usual presentation is pain and swelling Sites of involvement: Local - 58% Regional nodes - 16% Distant mets - 26% • >90% ALK negative JAMA 2008;300:2030 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 10
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 Follicular Lymphoma “In Situ” • A distinction has been made between this and “partial involvement” by follicular lymphoma 11
Diagnostic features of FLIS and PFL FLIS PFL Architecture intact Altered architecture Follicle size normal Follicle size often expanded Involved follicles widely scattered Involved follicles grouped together in LN Intact cuff with sharp edge to GC Blurred edge to GC and attenuated cuff Very strong expression of BCL2 and BCL2 and CD10 more variable in CD10 intensity Almost pure centrocytes Centrocytes with few centroblasts Atypical cells (CD10 + /BCL2 + B cells) may Atypical cells confined to GC be found outside the GC Jegalian, Blood 2011;118:2976 Clinical Results In 21 Cases (NCI) • Age 23-76 years (median 52) • Female – 67% • Developed follicular lymphoma – 5% Blood 2011;118:2976 12
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 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 20-40 yrs Joe Connors 13
Mediastinal Gray Zone Lymphoma PMBCL MGZL NSHL Median age 32 34 32 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 Comparative Outcomes of Primary Mediastinal B-Cell and Mediastinal Grey Zone Lymphomas Treated with Dose-adjusted EPOCH-R OS PFS Dunlevy, Blood 2009;114 (Abstract #106) 14
Conclusions – Mediastinal Gray Zone Lymphoma • It appears to be a distinct entity • More often localized than PMBCL • Most patients will require radiotherapy for cure • 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. 15
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 Cutaneous B-cell Lymphomas • MALT • Primary follicle center (indolent DLBCL) • Large B-cell lymphoma leg type (aggressive) 16
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 17
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