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(NCCN Guidelines®) Non-Hodgkin's Lymphomas 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® . Hairy Cell Leukemia NCCN Guidelines Version 2.2015 NCCN Guidelines Index NHL Table of Contents Hairy Cell Leukemia Discussion DIAGNOSISa WORKUP ESSENTIAL: ESSENTIAL: · Presence of characteristic hairy cells upon morphologic · Physical exam: Presence of enlarged spleen examination of peripheral blood and characteristic and/or liver; presence of peripheral infiltrate with increased reticulin in bone marrow biopsy lymphadenopathy (uncommon) samples. Dry tap is frequent. · Performance status · IHC and flow cytometry are essential for establishing the · Peripheral blood examination diagnosis and for distinguishing between hairy cell · CBC, differential, platelets b leukemia and hairy cell variant. · Comprehensive metabolic panel with particular · c,d Adequate immunophenotyping to establish diagnosis attention to renal function > See Initial IHC panel: CD20, CD25, CD123, cyclin D1 · LDH Treatment (HCL-2) or · Bone marrow biopsy ± aspirate > Cell surface marker analysis by flow cytometry: CD3, · Hepatitis B testinge if rituximab contemplated CD5, CD10, CD11c, CD19, CD20, CD22, CD25, CD103 · Pregnancy testing in women of child-bearing age USEFUL UNDER CERTAIN CIRCUMSTANCES: (if chemotherapy planned) · Molecular analysis to detect: IGHV mutational status USEFUL UNDER CERTAIN CIRCUMSTANCES: · · Sequencing ofBRAF for V600E mutation or IHC for Chest/abdominal/pelvic CT with contrast of mutant BRAF diagnostic quality · · Annexin A1 Discussion of fertility issues and sperm banking aThis guideline applies to hairy cell leukemia, not hairy cell variant. There are no dSee Use of Immunophenotyping/Genetic Testing in Differential Diagnosis of Mature sufficient data on treatment of hairy cell variant. B-Cell andNK/T-Cell Neoplasms (NHODG-A). bHairy cell variant is characteristically CD25- CD123-, annexin A1-. This helps to eHepatitis B testing is indicated because of the risk of reactivation with distinguish the variant form from classical HCL. immunotherapy + chemotherapy. Tests include hepatitis B surface antigen and cTypical immunophenotype: CD5-, CD10-, CD11c+, CD20+ (bright), CD22+, core antibody for a patient with no risk factors. For patients with risk factors or CD25+, CD103+, CD123+, cyclin D1+, annexin A1+. Monocytopenia is previous history of hepatitis B, add e-antigen. If positive, check viral load and characteristic. 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® . HCL-1 NCCN Guidelines Version 2.2015 NCCN Guidelines Index NHL Table of Contents Hairy Cell Leukemia Discussion INDICATION FOR INITIAL TREATMENTh FOLLOW-UP RELAPSED/ TREATMENT REFRACTORYh · Retreat with initial purine analog ± Relapse at rituximab ³1 year No · Alternative purine Observe indication analog± rituximab · Systemic symptoms Observe until Complete · Splenic discomfort indication for responseg · Recurrent infection treatment · Hemoglobin <12 g/dL · Platelets <100,000/mcL Progression Relapse at · ANC <1000/mcL <1 year Indication · Cladribinef present · Pentostatin Vemurafenibi · Clinical trial · Alternate purine < Complete Consider prophylaxis for tumor analog ± rituximab responseg lysis syndrome (See NHODG-B) · Interferon alpha · Rituximab alone See monoclonal antibody and viral reactivation (NHODG-B ) Adapted from: Grever MR. How I treat hairy cell leukemia. Blood 2010;115:21-28. fCladribine should not be administered to patients with active life-threatening or chronic infection. gComplete response defined as: recovery of blood counts (Hgb >12 g/dL, ANC >1500/mcL, platelet >100,000/mcL), absence of HCL cells by morphologic examination of bone marrow biopsy or peripheral blood samples, resolution of organomegaly by physical exam, and absence of disease symptoms. Eradication of minimal residual disease (as determined by flow cytometry, immunohistochemistry, or molecular analysis) is of unproven value at this point. hSee Treatment References (HCL-A). iShould be non-responsive to purine analog therapy. 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® . HCL-2 NCCN Guidelines Version 2.2015 NCCN Guidelines Index NHL Table of Contents Hairy Cell Leukemia Discussion TREATMENT REFERENCES Single-agent purine analogs Purine analogs with rituximab Flinn IW, Kopecky KJ, Foucar MK, et al. Long-term follow-up of remission duration, Else M, Osuji N, Forconi F, et al. The role of rituximab in combination with mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin. pentostatin or cladribine for the treatment of recurrent/refractory hairy cell Blood 2000;96:2981-2986. leukemia. Cancer 2007;110:2240-2247. Goodman GR, Burian C, Koziol JA, Saven A. Extended follow-up of patients with hairy cell Else M, Dearden CE, Matutes E, et al. Rituximab with pentostatin or cladribine: an leukemia after treatment with cladribine. J Clin Oncol 2003;21:891-896. effective combination treatment for hairy cell leukemia after disease recurrence. Zinzani PL, Tani M, Marchi E, et al. Long-term follow-up of front-line treatment of hairy cell Leuk Lymphoma 2011;52 Suppl 2:75-78. leukemia with 2-chlorodeoxyadenosine. Haematologica 2004;89:309-313. Ravandi F, O'Brien S, Jorgensen J, et al. Phase 2 study of cladribine followed by Chadha P, Rademaker AW, Mendiratta P, et al. Treatment of hairy cell leukemia with 2- rituximab in patients with hairy cell leukemia. Blood 2011;118:3818-3823. chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University Gerrie AS, Zypchen LN, Connors JM. Fludarabine and rituximab for relapsed or experience. Blood 2005;106:241-246. refractory hairy cell leukemia. Blood 2012;119:1988-1991. Robak T, Jamroziak K, Gora-Tybor J, et al. Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group Interferon-alpha (PALG) of a prospective, randomized, multicenter trial. Blood 2007;109:3672-3675. Damasio EE, Clavio M, Masoudi B, et al. Alpha-interferon as induction and Else M, Dearden CE, Matutes E, et al. Long-term follow-up of 233 patients with hairy cell maintenance therapy in hairy cell leukemia: a long-term follow-up analysis. Eur J leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from Haematol 2000;64:47-52. diagnosis. Br J Haematol 2009;145:733-740. Benz R, Siciliano RD, Stussi G, Fehr J. Long-term follow-up of interferon-alpha Zenhausern R, Schmitz SF, Solenthaler M, et al. Randomized trial of daily versus weekly induction and low-dose maintenance therapy in hairy cell leukemia. Eur J administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter Haematol 2009;82:194-200. phase III trial (SAKK 32/98). Leuk Lymphoma 2009;50:1501-1511. Dearden CE, Else M, Catovsky D. Long-term results for pentostatin and cladribine Vemurafenib treatment of hairy cell leukemia. Leuk Lymphoma 2011;52 Suppl 2:21-24. Tiacci E, et al. Vemurafenib is highly effective in hairy cell leukemia [abstract]. Grever M, Kopecky K, Foucar MK, et al. Randomized comparison of pentostatin versus Haematologica 2014;99(s1): Abstract S696. interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol 1995;13:974-982. Tallman MS, Hakimian D, Variakojis D, et al. A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. Blood 1992;80:2203-2209. Kraut EH, Bouroncle BA, Grever MR. Low-dose deoxycoformycin in the treatment of hairy cell leukemia. Blood 1986;68:1119-1122. Rituximab Lauria F, Lenoci M, Annino L, et al. Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia. Haematologica 2001;86:1046- 1050. Nieva J, Bethel K, Saven A. Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood 2003;102:810-813. Thomas DA, O'Brien S, Bueso-Ramos C, et al. Rituximab in relapsed or refractory hairy cell leukemia. Blood 2003;102:3906-3911. 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
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