Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

General principles of hematopoietic cell transplantation for acute lymphoblastic leukemia in adults

Richard A Larson, MD
Section Editor
Robert S Negrin, MD
Deputy Editor
Alan G Rosmarin, MD


The results of treatment of adults with acute lymphoblastic leukemia (ALL) have steadily improved and currently complete remission (CR) can be induced in 75 to 90 percent of patients. However, in contrast to ALL in children, relapse rates remain high and long-term survival rates are approximately 25 to 50 percent, depending upon patient age and disease characteristics [1,2]. (See "Induction therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults".)

The potential benefits of allogeneic hematopoietic cell transplantation (allo-HCT) are due to both the myeloablative chemoradiotherapy and the immune-mediated reaction of donor lymphocytes directed against residual ALL cells in the recipient (ie, the graft-versus-leukemia reaction). To be effective, the survival benefit should outweigh the greater expense and higher risk of early toxicity and death, and late complications such as graft versus host disease (GVHD) and sterility. Allo-HCT is commonly used as part of the post-remission therapy of patients with ALL demonstrating high-risk features, such as the presence of the Philadelphia (Ph) chromosome or a Ph-like molecular signature. Results have been best when allo-HCT is performed in first complete remission (CR), but allo-HCT can also cure some patients in second CR.

This topic review will discuss general issues in hematopoietic cell transplantation for ALL in adults including: selection of the donor, preparative chemoradiotherapy, and the graft-versus-leukemia effect. Outcomes with this procedure in different subsets of adults with ALL are discussed separately. (See "Donor selection for hematopoietic cell transplantation" and "Post-remission therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults".)

The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term for transplantation of progenitor cells from any source (eg, bone marrow, peripheral blood, umbilical 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 preferred donor for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for ALL is an HLA-matched sibling or matched unrelated donor (MUD). However, fewer than 25 percent of patients in the transplantable age group have an HLA-matched sibling donor. Allo-HCT using a partially matched family member donor or umbilical cord blood is a reasonable option for patients who do not have an HLA-identical matched donor [2,3]. (See "Sources of hematopoietic stem cells".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Feb 2017. | This topic last updated: Feb 06, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Juliusson G, Karlsson K, Lazarevic VLj, et al. Hematopoietic stem cell transplantation rates and long-term survival in acute myeloid and lymphoblastic leukemia: real-world population-based data from the Swedish Acute Leukemia Registry 1997-2006. Cancer 2011; 117:4238.
  2. Oliansky DM, Larson RA, Weisdorf D, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence-based review. Biol Blood Marrow Transplant 2012; 18:16.
  3. Nishiwaki S, Miyamura K, Ohashi K, et al. Impact of a donor source on adult Philadelphia chromosome-negative acute lymphoblastic leukemia: a retrospective analysis from the Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Ann Oncol 2013; 24:1594.
  4. Weisdorf DJ, Billett AL, Hannan P, et al. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia. Blood 1997; 90:2962.
  5. Speiser DE, Tiercy JM, Rufer N, et al. High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation. Blood 1996; 87:4455.
  6. Ringdén O, Labopin M, Gluckman E, et al. Donor search or autografting in patients with acute leukaemia who lack an HLA-identical sibling? A matched-pair analysis. Acute Leukaemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation (EBMT) and the International Marrow Unrelated Search and Transplant (IMUST) Study. Bone Marrow Transplant 1997; 19:963.
  7. Cornelissen JJ, Carston M, Kollman C, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood 2001; 97:1572.
  8. Marks DI, Pérez WS, He W, et al. Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission. Blood 2008; 112:426.
  9. Nishiwaki S, Inamoto Y, Sakamaki H, et al. Allogeneic stem cell transplantation for adult Philadelphia chromosome-negative acute lymphocytic leukemia: comparable survival rates but different risk factors between related and unrelated transplantation in first complete remission. Blood 2010; 116:4368.
  10. Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 2005; 23:3447.
  11. Mo XD, Xu LP, Zhang XH, et al. Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia: no difference in the high- and low-risk groups. Int J Cancer 2015; 136:1697.
  12. Longo DL. Chemotherapy for advanced aggressive lymphoma: more is better ...isn't it? J Clin Oncol 1990; 8:952.
  13. Sutton L, Kuentz M, Cordonnier C, et al. Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities. Bone Marrow Transplant 1993; 12:583.
  14. Robinson N, Sullivan KM. Complications of allogeneic bone marrow transplantation. Curr Opin Hematol 1994; 1:406.
  15. Belkacemi Y, Labopin M, Vernant JP, et al. Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the European Group for Blood and Marrow Transplantation. Int J Radiat Oncol Biol Phys 1998; 41:659.
  16. Woods WG, Ramsay NK, Weisdorf DJ, et al. Bone marrow transplantation for acute lymphocytic leukemia utilizing total body irradiation followed by high doses of cytosine arabinoside: lack of superiority over cyclophosphamide-containing conditioning regimens. Bone Marrow Transplant 1990; 6:9.
  17. Herzig RH, Coccia PF, Lazarus HM, et al. Bone marrow transplantation for acute leukemia and lymphoma with high-dose cytosine arabinoside and total body irradiation. Semin Oncol 1985; 12:184.
  18. Champlin R, Gale RP. Acute lymphoblastic leukemia: recent advances in biology and therapy. Blood 1989; 73:2051.
  19. Weisdorf DJ, Woods WG, Nesbit ME Jr, et al. Allogeneic bone marrow transplantation for acute lymphoblastic leukaemia: risk factors and clinical outcome. Br J Haematol 1994; 86:62.
  20. Snyder DS, Chao NJ, Amylon MD, et al. Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission. Blood 1993; 82:2920.
  21. Blume KG, Kopecky KJ, Henslee-Downey JP, et al. A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study. Blood 1993; 81:2187.
  22. Marks DI, Forman SJ, Blume KG, et al. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant 2006; 12:438.
  23. Copelan EA, Deeg HJ. Conditioning for allogeneic marrow transplantation in patients with lymphohematopoietic malignancies without the use of total body irradiation. Blood 1992; 80:1648.
  24. Copelan EA, Biggs JC, Avalos BR, et al. Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia. J Clin Oncol 1992; 10:237.
  25. Marks DI, Wang T, Pérez WS, et al. The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission. Blood 2010; 116:366.
  26. Mohty M, Labopin M, Volin L, et al. Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood 2010; 116:4439.
  27. Gale RP, Horowitz MM, Ash RC, et al. Identical-twin bone marrow transplants for leukemia. Ann Intern Med 1994; 120:646.
  28. Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86:2041.
  29. Slavin S, Naparstek E, Nagler A, et al. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Blood 1996; 87:2195.
  30. Tzeng CH, Lin JS, Lee JC, et al. Transfusion of donor peripheral blood buffy coat cells as effective treatment for relapsed acute leukemia after transplantation of allogeneic bone marrow or peripheral blood stem cells from the same donor. Transfusion 1996; 36:685.
  31. Socié G, Stone JV, Wingard JR, et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med 1999; 341:14.
  32. Uzunel M, Mattsson J, Jaksch M, et al. The significance of graft-versus-host disease and pretransplantation minimal residual disease status to outcome after allogeneic stem cell transplantation in patients with acute lymphoblastic leukemia. Blood 2001; 98:1982.
  33. Lee S, Kim DW, Cho B, et al. Risk factors for adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia in remission treated with allogeneic bone marrow transplantation: the potential of real-time quantitative reverse-transcription polymerase chain reaction. Br J Haematol 2003; 120:145.
  34. Barrett AJ, Horowitz MM, Gale RP, et al. Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival. Blood 1989; 74:862.
  35. Doney K, Fisher LD, Appelbaum FR, et al. Treatment of adult acute lymphoblastic leukemia with allogeneic bone marrow transplantation. Multivariate analysis of factors affecting acute graft-versus-host disease, relapse, and relapse-free survival. Bone Marrow Transplant 1991; 7:453.