Hematopoietic cell transplantation in chronic lymphocytic leukemia
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
- Kanti R Rai, MD
Kanti R Rai, MD
- Professor of Medicine and Molecular Medicine
- Hofstra North Shore-LIJ School of Medicine at Hofstra University
Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms). It is characterized by a progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin.
CLL is considered to be identical (ie, one disease at different stages) to the mature (peripheral) B-cell neoplasm small lymphocytic lymphoma (SLL), one of the indolent non-Hodgkin lymphomas. The term CLL is used when the disease manifests primarily in the bone marrow and blood, while the term SLL is used when involvement is primarily nodal. While there are some differences in the treatment of early stage CLL and SLL, the treatment of advanced stage disease is the same. (See "Clinical presentation, pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia".)
The natural history of CLL is extremely variable. While many cases follow an indolent course that is well controlled with standard therapy, others progress rapidly and die within two to three years after diagnosis from complications or causes directly related to CLL. The initial treatment of symptomatic CLL primarily consists of an immunotherapy-based chemotherapy regimen (eg, rituximab plus chemotherapy). (See "Overview of the treatment of chronic lymphocytic leukemia" and "Staging and prognosis of chronic lymphocytic leukemia" and "Overview of the complications of chronic lymphocytic leukemia".)
The use of either autologous or allogeneic hematopoietic cell transplantation (HCT) in CLL is an emerging therapy for selected patients and is the subject of ongoing clinical trials. Autologous HCT is not curative, but may result in prolonged remissions and has a low treatment-related mortality rate. In comparison, allogeneic HCT may cure a percentage of patients with CLL, but is associated with higher treatment-related mortality. The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of progenitor cells from any source (eg, bone marrow, peripheral blood, cord blood). Otherwise, the source of such cells will be specified (eg, autologous peripheral blood progenitor cell transplantation). (See "Sources of hematopoietic stem cells".)
The use of HCT in CLL is reviewed below. Other treatment options are presented separately. (See "Treatment of relapsed or refractory chronic lymphocytic leukemia".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Moreno C, Villamor N, Colomer D, et al. Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J Clin Oncol 2005; 23:3433.
- Gribben JG, Zahrieh D, Stephans K, et al. Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia. Blood 2005; 106:4389.
- Rondón G, Giralt S, Huh Y, et al. Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. Bone Marrow Transplant 1996; 18:669.
- Marks DI, Lush R, Cavenagh J, et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100:3108.
- Mehta J, Powles R, Singhal S, et al. Clinical and hematologic response of chronic lymphocytic and prolymphocytic leukemia persisting after allogeneic bone marrow transplantation with the onset of acute graft-versus-host disease: possible role of graft-versus-leukemia. Bone Marrow Transplant 1996; 17:371.
- Michallet M, Corront B, Hollard D, et al. Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG. Bone Marrow Transplant 1991; 7:275.
- Rabinowe SN, Soiffer RJ, Gribben JG, et al. Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia. Blood 1993; 82:1366.
- Khouri IF, Keating MJ, Vriesendorp HM, et al. Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results. J Clin Oncol 1994; 12:748.
- Malhotra P, Hogan WJ, Litzow MR, et al. Long-term outcome of allogeneic stem cell transplantation in chronic lymphocytic leukemia: analysis after a minimum follow-up of 5 years. Leuk Lymphoma 2008; 49:1724.
- Khouri IF, Przepiorka D, van Besien K, et al. Allogeneic blood or marrow transplantation for chronic lymphocytic leukaemia: timing of transplantation and potential effect of fludarabine on acute graft-versus-host disease. Br J Haematol 1997; 97:466.
- Khouri IF, Keating MJ, Saliba RM, Champlin RE. Long-term follow-up of patients with CLL treated with allogeneic hematopoietic transplantation. Cytotherapy 2002; 4:217.
- Sorror ML, Maris MB, Sandmaier BM, et al. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol 2005; 23:3819.
- Sorror ML, Storer BE, Sandmaier BM, et al. Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol 2008; 26:4912.
- Dreger P, Döhner H, Ritgen M, et al. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood 2010; 116:2438.
- Sorror ML, Storer BE, Maloney DG, et al. Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood 2008; 111:446.
- Delgado J, Pillai S, Phillips N, et al. Does reduced-intensity allogeneic transplantation confer a survival advantage to patients with poor prognosis chronic lymphocytic leukaemia? A case-control retrospective analysis. Ann Oncol 2009; 20:2007.
- Khouri IF, Bassett R, Poindexter N, et al. Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia: long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility antigen subtype on outcome. Cancer 2011; 117:4679.
- Brown JR, Kim HT, Armand P, et al. Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome. Leukemia 2013; 27:362.
- Khouri IF, Wei W, Korbling M, et al. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood 2014; 124:2306.
- Dreger P, Schnaiter A, Zenz T, et al. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood 2013; 121:3284.
- Schetelig J, Thiede C, Bornhauser M, et al. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol 2003; 21:2747.
- Ritgen M, Stilgenbauer S, von Neuhoff N, et al. Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 2004; 104:2600.
- Khouri IF, Saliba RM, Admirand J, et al. Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia. Br J Haematol 2007; 137:355.
- Delgado J, Thomson K, Russell N, et al. Results of alemtuzumab-based reduced-intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study. Blood 2006; 107:1724.
- Arai S, Sahaf B, Narasimhan B, et al. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood 2012; 119:6145.
- Milligan DW, Fernandes S, Dasgupta R, et al. Results of the MRC pilot study show autografting for younger patients with chronic lymphocytic leukemia is safe and achieves a high percentage of molecular responses. Blood 2005; 105:397.
- Dreger P, Stilgenbauer S, Benner A, et al. The prognostic impact of autologous stem cell transplantation in patients with chronic lymphocytic leukemia: a risk-matched analysis based on the VH gene mutational status. Blood 2004; 103:2850.
- Dreger P, Döhner H, McClanahan F, et al. Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial. Blood 2012; 119:4851.
- Michallet M, Dreger P, Sutton L, et al. Autologous hematopoietic stem cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation. Blood 2011; 117:1516.
- de Wreede LC, Watson M, van Os M, et al. Improved relapse-free survival after autologous stem cell transplantation does not translate into better quality of life in chronic lymphocytic leukemia: lessons from the randomized European Society for Blood and Marrow Transplantation-Intergroup study. Am J Hematol 2014; 89:174.
- Sutton L, Chevret S, Tournilhac O, et al. Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC. Blood 2011; 117:6109.
- Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival. Exp Hematol 2004; 32:28.
- Rozovski U, Benjamini O, Jain P, et al. Outcomes of Patients With Chronic Lymphocytic Leukemia and Richter's Transformation After Transplantation Failure. J Clin Oncol 2015; 33:1557.
- Ryan CE, Sahaf B, Logan AC, et al. Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT. Blood 2016; 128:2899.
- Link CS, Teipel R, Heidenreich F, et al. Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation. Bone Marrow Transplant 2016; 51:793.
- DETERMINING TRANSPLANT ELIGIBILITY
- TIMING OF TRANSPLANT
- Previously untreated disease
- Relapsed or refractory disease
- Following histologic transformation
- TYPE OF TRANSPLANTATION
- Allogeneic HCT
- - Myeloablative HCT
- - Nonmyeloablative HCT
- Autologous HCT
- TREATMENT OF RELAPSE AFTER HCT
- INFORMATION FOR PATIENTS