NCCN Guidelines Index NHL Table of Contents Discussion NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® ) Non-Hodgkin’s Lymphomas Version 2.2015 NCCN.org Continue Version 2.2015, 03/03/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® . Diffuse Large B-Cell Lymphoma NCCN Guidelines Version 2.2015 NCCN Guidelines Index NHL Table of Contents Diffuse Large B-Cell Lymphoma Discussion DIAGNOSISa,b SUBTYPES ESSENTIAL: · Hematopathology review of all slides with at least one paraffin block representative of the tumor. Rebiopsy if consult material is nondiagnostic. · An FNA or core needle biopsy alone is not generally suitable for the initial diagnosis of lymphoma. In certain · Subtypes included: circumstances, when a lymph node is not easily accessible > DLBCL, NOSf for excisional or incisional biopsy, a combination of core > DLBCL coexistent with follicular lymphoma of any grade biopsy and FNA biopsies in conjunction with appropriate > DLBCL coexistent with gastric MALT lymphoma > DLBCL coexistent with nongastric MALT lymphoma See ancillary techniques for the differential diagnosis Workup > Follicular lymphoma grade 3g (immunohistochemistry, flow cytometry, PCR for IgH and (BCEL-2) TCR gene rearrangements, and FISH for major > Intravascular large B-cell lymphoma translocations) may be sufficient for diagnosis. > DLBCL associated with chronic inflammation > · Adequate immunophenotyping to establish diagnosis and ALK-positive DLBCL > GCB versus non-GCB originc,d EBV-positive DLBCL of the elderly > > IHC panel: CD20, CD3, CD5, CD10, CD45, BCL2, BCL6, T-cell-/histiocyte-rich large B-cell lymphoma Ki-67, IRF4/MUM1, MYC or · > Cell surface marker analysis by flow cytometry: Subtypesnot included: > kappa/lambda, CD45, CD3, CD5, CD19, CD10, CD20 Primary cutaneous B-cell lymphomas (See CUTB-1 ) > USEFUL UNDER CERTAIN CIRCUMSTANCES: Primary DLBCL of the CNS (See NCCN Guidelines for CNS ) · Additional immunohistochemical studies to establish lymphoma subtype Primary Mediastinal Large B-Cell Lymphoma (PMBL), see BCEL-B 1 of 2. > IHC panel:Cyclin D1 , kappa/lambda, CD30, CD138, Grey Zone Lymphoma, see BCEL-B 2 of 2. EBER-ISH, ALK, HHV8 · e Cytogenetics or FISH: t(14;18), t(3;v), t(8;14), t(8;v) dSee Use of Immunophenotyping/Genetic Testing in Differential Diagnosis of Mature B- Cell and NK/T-Cell Neoplasms (NHODG-A). eThere are no established guidelines to select DLBCL patients to investigate for aBurkitt lymphoma intermediate histology or DLBCL CD10+ tumors with very double-hit lymphomas. Standard of care is not established for DLBCL with t(14;18) high proliferation >90% with or without Burkitt lymphoma-like features might with concurrent MYC rearrangements. be considered for more aggressive treatment as perBURK-A . These cases fGerminal center (or follicle center) phenotype is not equivalent to follicular lymphoma would be appropriate to evaluate forBCL2 , BCL6, and MYC rearrangements. and can occur in DLBCL and Burkitt lymphoma. Morphology is required to establish bSee International Prognostic Index (BCEL-A). diagnosis. cTypical immunophenotype: CD20+, CD45+, CD3-; other markers used for gControversy exists regarding management of FL grade 3. Some may treat FL grade 3a subclassification. as follicular lymphoma and others may treat it as DLBCL. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 2.2015, 03/03/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® . BCEL-1 NCCN Guidelines Version 2.2015 NCCN Guidelines Index NHL Table of Contents Diffuse Large B-Cell Lymphoma Discussion WORKUP ESSENTIAL: · Physical exam: attention to node-bearing areas, including Waldeyer’s ring, and to size of liver and spleen · Performance status · B symptoms · CBC, differential, platelets · LDH · Comprehensive metabolic panel · Uric acid · Chest/abdominal/pelvic CT with contrast of diagnostic quality and/or PET-CT scan · Adequate bone marrow biopsy (>1.6 cm) ± aspirate; bone marrow may not be needed if PET scan negative unless finding of another See Induction lymphoma subtype is important for treatment decision Therapy (BCEL-3) · Calculation of International Prognostic Index (IPI)b · Hepatitis B testingh · MUGA scan/echocardiogram if anthracycline or anthracenedione- based regimen is indicated · Pregnancy testing in women of child-bearing age USEFUL IN SELECTED CASES: · Neck CT, head CT, or MRI · Discussion of fertility issues and sperm banking · HIV · Lumbar puncture, consider if paranasal sinus, testicular, epidural, bone marrow with large cell lymphoma, HIV lymphoma, or³ 2 extranodal sites and elevated LDH · Beta-2-microglobulin bSee International Prognostic Index (BCEL-A). hHepatitis B testing is indicated because of the risk of reactivation with immunotherapy + chemotherapy. Tests include hepatitis B surface antigen and core antibody for a patient with no risk factors. For patients with risk factors or previous history of hepatitis B, add e-antigen. If positive, check viral load and consult with gastroenterologist. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 2.2015, 03/03/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® . BCEL-2 NCCN Guidelines Version 2.2015 NCCN Guidelines Index NHL Table of Contents Diffuse Large B-Cell Lymphoma Discussion STAGE INDUCTION THERAPYm Consider prophylaxis for tumor lysis syndrome (See NHODG-B) See monoclonal antibody and RCHOPno x 3 cycles + RT See Pre RT viral reactivation (NHODG-B ) Nonbulky or Evaluation (<7.5 cm) RCHOPno x 6 cycles ± RT (BCEL-4) Stage I, IIi,j See Pre RT Bulky RCHOPn x 6 cycles± RTo (category 1) Evaluation (³7.5 cm) (BCEL-4) Clinical trialp Stage III, IVi,k,l or See Interim RCHOPqr (category 1) After 2–4 cycles Restaging (BCEL-5) iIn testicular lymphoma, after completion of chemotherapy, scrotal RT should be given (25–30 Gy). l j For systemic disease with concurrent CNS disease, see BCEL-C. In patients who are not candidates for chemotherapy, involved-site radiation m therapy (ISRT) is recommended. Recommendations are for HIV-negative lymphoma only. k For HIV-positive DLBCL, see AIDS-2. In selected cases (paranasal sinus, testicular, epidural, bone marrow with large n cell lymphoma, HIV lymphoma, kidney or adrenal gland involvement, concurrent For patients who cannot tolerate anthracyclines, seeBCEL-C for regimens for ³ patients with poor left ventricular function. expression of MYC and BCL2 protein, or 2 extranodal sites and elevated LDH), o there may be an increased risk of CNS events. The optimal management of See Principles of Radiation Therapy (NHODG-D ). p these events is uncertain, but CNS prophylaxis can be considered with 4–8 May include high-dose therapy. doses of intrathecal methotrexate and/or cytarabine, or systemic methotrexate qBased on current clinical trials, CHOP is preferable due to reduced toxicities, but (3–3.5 g/m2 ) during the course of treatment. Recent data regarding stage IE other comparable anthracycline-based regimens are acceptable (see BCEL-C). DLBCL of the breast have been suggested as a potential risk for CNS disease. rIn selected cases, RT to initially bulky sites of disease may be beneficial See Prognostic Model for Assessing Risk of CNS Disease (BCEL-A 2 of 2). (category 2B). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Version 2.2015, 03/03/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN® . BCEL-3 NCCN Guidelines Version 2.2015 NCCN Guidelines Index NHL Table of Contents Diffuse Large B-Cell Lymphoma Discussion PRE RT EVALUATION FOLLOW-UP END OF INITIAL RESPONSE FOLLOW-UP (End of induction THERAPY TREATMENT (after completion of chemoimmunotherapy) RESTAGING induction chemotherapy) Clinical · H&P and labs, Complete Complete planned t every 3–6 mo for response course of treatmentv (PET negative) 5 y and then yearly or as clinically Complete Complete course of indicated At completion of t,w Relapse, therapy with higher RT response Imaging treatment, repeat See doseo,v · Repeat CT scan Stage I, II: all positive Relapse or Pre RT or v only as clinically If PET+ after 6 cycles of studies. If PET-CT Refractory evaluation, s indicated Disease RCHOP, high-dose scan positive, repeat all (BCEL-6) therapy with autologous rebiopsy before positive studies. Partial Partial t,u stem cell rescue ± RT changing course If PET-CT scans response responset pre- or post-transplantu of treatment. positive, (PET positive) or rebiopsy before Clinical trialu (may No response changing include allogeneic stem or course of cell