NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019

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Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.

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PLEASE NOTE

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. The NCCN Guidelines Insights highlight important changes in the NCCN Guidelines recommendations from previous versions. Colored markings in the algorithm show changes and the discussion aims to further the understanding of these changes by summarizing salient portions of the panel's discussion, including the literature reviewed.

The NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their application or use in any way.

The complete and most recent of these NCCN Guidelines is available free of charge at NCCN.org.

© National Comprehensive Cancer Network, Inc. 2019. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.

  • 1.

    A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997;89:39093918.

    • Search Google Scholar
    • Export Citation
  • 2.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:730.

  • 3.

    Tsimberidou AM, Keating MJ. Richter syndrome: biology, incidence, and therapeutic strategies. Cancer 2005;103:216228.

  • 4.

    Tsimberidou AM, O'Brien S, Kantarjian HM. Hodgkin transformation of chronic lymphocytic leukemia: the M. D. Anderson cancer center experience. Cancer 2006;107:12941302.

    • Search Google Scholar
    • Export Citation
  • 5.

    Bockorny B, Codreanu I, Dasanu CA. Hodgkin lymphoma as Richter transformation in chronic lymphocytic leukaemia: a retrospective analysis of world literature. Br J Haematol 2012;156:5066.

    • Search Google Scholar
    • Export Citation
  • 6.

    Tsimberidou AM, O'Brien S, Khouri I. Clinical outcomes and prognostic factors in patients with richter's syndrome treated with chemotherapy or chemoimmunotherapy with or without stem-cell transplantation. J Clin Oncol 2006;24:23432351.

    • Search Google Scholar
    • Export Citation
  • 7.

    Rossi D, Spina V, Cerri M. Stereotyped B-cell receptor is an independent risk factor of chronic lymphocytic leukemia transformation to Richter syndrome. Clin Cancer Res 2009;15:44154422.

    • Search Google Scholar
    • Export Citation
  • 8.

    Rossi D, Spina V, Deambrogi C. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood 2011;117:33913401.

    • Search Google Scholar
    • Export Citation
  • 9.

    Parikh SA, Rabe KG, Call TG. Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients. Br J Haematol 2013;162:774782.

    • Search Google Scholar
    • Export Citation
  • 10.

    Scandurra M, Rossi D, Deambrogi C. Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas. Hematol Oncol 2010;28:6267.

    • Search Google Scholar
    • Export Citation
  • 11.

    Rossi D, Rasi S, Spina V. Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome. Br J Haematol 2012;158:426429.

    • Search Google Scholar
    • Export Citation
  • 12.

    Villamor N, Conde L, Martinez-Trillos A. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia 2013;27:11001106.

    • Search Google Scholar
    • Export Citation
  • 13.

    Chigrinova E, Rinaldi A, Kwee I. Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome. Blood 2013;122:26732682.

    • Search Google Scholar
    • Export Citation
  • 14.

    Fabbri G, Khiabanian H, Holmes AB. Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome. J Exp Med 2013;210:22732288.

    • Search Google Scholar
    • Export Citation
  • 15.

    Kadri S, Lee J, Fitzpatrick C. Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL. Blood Adv 2017;1:715727.

    • Search Google Scholar
    • Export Citation
  • 16.

    Innocenti I, Rossi D, Trape G. Clinical, pathological, and biological characterization of Richter syndrome developing after ibrutinib treatment for relapsed chronic lymphocytic leukemia [published online February 27, 2018]. Hematol Oncol. doi: 10.1002/hon.2502

    • Search Google Scholar
    • Export Citation
  • 17.

    Anderson MA, Tam C, Lew TE. Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax. Blood 2017;129:33623370.

    • Search Google Scholar
    • Export Citation
  • 18.

    Gine E, Martinez A, Villamor N. Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (“accelerated” chronic lymphocytic leukemia) with aggressive clinical behavior. Haematologica 2010;95:15261533.

    • Search Google Scholar
    • Export Citation
  • 19.

    Bruzzi JF, Macapinlac H, Tsimberidou AM. Detection of Richter's transformation of chronic lymphocytic leukemia by PET/CT. J Nucl Med 2006;47:12671273.

    • Search Google Scholar
    • Export Citation
  • 20.

    Noy A, Schoder H, Gonen M. The majority of transformed lymphomas have high standardized uptake values (SUVs) on positron emission tomography (PET) scanning similar to diffuse large B-cell lymphoma (DLBCL). Ann Oncol 2009;20:508512.

    • Search Google Scholar
    • Export Citation
  • 21.

    Falchi L, Keating MJ, Marom EM. Correlation between FDG/PET, histology, characteristics, and survival in 332 patients with chronic lymphoid leukemia. Blood 2014;123:27832790.

    • Search Google Scholar
    • Export Citation
  • 22.

    Papajik T, Myslivecek M, Urbanova R. 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography examination in patients with chronic lymphocytic leukemia may reveal Richter transformation. Leuk Lymphoma 2014;55:314319.

    • Search Google Scholar
    • Export Citation
  • 23.

    Michallet AS, Sesques P, Rabe KG. An 18F-FDG-PET maximum standardized uptake value > 10 represents a novel valid marker for discerning Richter's syndrome. Leuk Lymphoma 2016;57:14741477.

    • Search Google Scholar
    • Export Citation
  • 24.

    Mato AR, Wierda WG, Davids MS. Analysis of PET-CT to identify Richter's transformation in 167 patients with disease progression following kinase inhibitor therapy [abstract]. Blood 2017;130:Abstract 834.

    • Search Google Scholar
    • Export Citation
  • 25.

    Ansell SM, Li CY, Lloyd RV, Phyliky RL. Epstein-Barr virus infection in Richter's transformation. Am J Hematol 1999;60:99104.

  • 26.

    Xiao W, Chen WW, Sorbara L. Hodgkin lymphoma variant of Richter transformation: morphology, Epstein-Barr virus status, clonality, and survival analysis-with comparison to Hodgkin-like lesion. Hum Pathol 2016;55:108116.

    • Search Google Scholar
    • Export Citation
  • 27.

    Mao Z, Quintanilla-Martinez L, Raffeld M. IgVH mutational status and clonality analysis of Richter's transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution. Am J Surg Pathol 2007;31:16051614.

    • Search Google Scholar
    • Export Citation
  • 28.

    Langerbeins P, Busch R, Anheier N. Poor efficacy and tolerability of R-CHOP in relapsed/refractory chronic lymphocytic leukemia and Richter transformation. Am J Hematol 2014;89:E239243.

    • Search Google Scholar
    • Export Citation
  • 29.

    Rogers KA, Huang Y, Ruppert AS. A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor. Br J Haematol 2018;180:259266.

    • Search Google Scholar
    • Export Citation
  • 30.

    Tsimberidou AM, Kantarjian HM, Cortes J. Fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone plus rituximab and granulocyte-macrophage-colony stimulating factor (GM-CSF) alternating with methotrexate and cytarabine plus rituximab and GM-CSF in patients with Richter syndrome or fludarabine-refractory chronic lymphocytic leukemia. Cancer 2003;97:17111720.

    • Search Google Scholar
    • Export Citation
  • 31.

    Dabaja BS, O'Brien SM, Kantarjian HM. Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoXome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome. Leuk Lymphoma 2001;42:329337.

    • Search Google Scholar
    • Export Citation
  • 32.

    Tsimberidou AM, Wierda WG, Plunkett W. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2008;26:196203.

    • Search Google Scholar
    • Export Citation
  • 33.

    Tsimberidou AM, Wierda WG, Wen S. Phase I-II clinical trial of oxaliplatin, fludarabine, cytarabine, and rituximab therapy in aggressive relapsed/refractory chronic lymphocytic leukemia or Richter syndrome. Clin Lymphoma Myeloma Leuk 2013;13:568574.

    • Search Google Scholar
    • Export Citation
  • 34.

    Cwynarski K, van Biezen A, de Wreede L. Autologous and allogeneic stem-cell transplantation for transformed chronic lymphocytic leukemia (Richter's syndrome): a retrospective analysis from the chronic lymphocytic leukemia subcommittee of the chronic leukemia working party and lymphoma working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2012;30:22112217.

    • Search Google Scholar
    • Export Citation
  • 35.

    Kharfan-Dabaja MA, Kumar A, Stingo FE. Allogeneic hematopoietic cell transplantation for Richter syndrome: a single-center experience. Clin Lymphoma Myeloma Leuk 2018;18:e3539.

    • Search Google Scholar
    • Export Citation
  • 36.

    Jain N, Basu S, Thompson PA. Nivolumab combined with ibrutinib for CLL and Richter transformation: a phase II trial [abstract]. Blood 2016;128:Abstract 59.

    • Search Google Scholar
    • Export Citation
  • 37.

    Younes A, Brody J, Carpio C. Safety and efficacy of the combination of ibrutinib and nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia [abstract]. Blood 2017;130:Abstract 833.

    • Search Google Scholar
    • Export Citation
  • 38.

    Ding W, LaPlant BR, Call TG. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood 2017;129:34193427.

  • 39.

    Rogers KA, Huang Y, Dotson E. Use of PD-1 (PDCD1) inhibitors for the treatment of Richter syndrome: experience at a single academic centre [published online July 20, 2018]. Br J Haematol. doi: 10.1111/bjh.15508

    • Search Google Scholar
    • Export Citation
  • 40.

    Tadmor T, Shvidel L, Goldschmidt N. Hodgkin's variant of Richter transformation in chronic lymphocytic leukemia; a retrospective study from the Israeli CLL study group. Anticancer Res 2014;34:785790.

    • Search Google Scholar
    • Export Citation
  • 41.

    Parikh SA, Habermann TM, Chaffee KG. Hodgkin transformation of chronic lymphocytic leukemia: Incidence, outcomes, and comparison to de novo Hodgkin lymphoma. Am J Hematol 2015;90:334338.

    • Search Google Scholar
    • Export Citation
  • 42.

    Mauro FR, Galieni P, Tedeschi A. Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma. Am J Hematol 2017;92:529535.

    • Search Google Scholar
    • Export Citation
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