Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Allogeneic transplantation for ALL in adults

Abstract

Allogeneic transplantation is an effective treatment for adult patients with high-risk ALL, including patients in first or second remission. Although only a few studies have evaluated the optimal transplant regimens, the data would suggest that a TBI-based regimen results in better disease control. Although not as potent as it is in other hematologic malignancies, the GVL effect is an important component of achieving cure of ALL. Because of the toxicity of the fully ablative regimen, reduced-intensity transplants are being explored in older patients with ALL when the prognosis is especially poor with standard chemotherapy.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

References

  1. Hoelzer D, Ludwig WD, Thiel E, Gassmann W, Löffler H, Fonatsch C et al. Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 1996; 87: 495–508.

    CAS  PubMed  Google Scholar 

  2. Laport GF, Larson RA . Treatment of adult acute lymphoblastic leukemia. Semin Oncol 1997; 24: 70–82.

    CAS  PubMed  Google Scholar 

  3. Hoelzer D, Gökbuget N . New approaches to acute lymphoblastic leukemia in adults: where do we go? Semin Oncol 2000; 27: 540–559.

    CAS  PubMed  Google Scholar 

  4. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 2005; 106: 3760–3767.

    CAS  Article  Google Scholar 

  5. Faderl S, Kantarjian M, Talpaz M, Estrov Z . Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia. Blood 1998; 91: 3996–4019.

    Google Scholar 

  6. Graux C, Cools J, Michaux L, Vandenberghe P, Hagemeijer A . Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia 2006; 20: 1496–1510.

    CAS  Article  Google Scholar 

  7. Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 2007; 109: 3189.

    CAS  Article  Google Scholar 

  8. Hoelzer D, Goekbuget N, Ottmann OG . Targeted therapies in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Semin Hematol 2002; 39: 32–37.

    CAS  Article  Google Scholar 

  9. Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004; 103: 4396–4407.

    CAS  Article  Google Scholar 

  10. Wassmann B, Pfeifer H, Goekbuget N, Beelen DW, Beck J, Stelljes M et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Blood 2006; 108: 1469–1477.

    CAS  Article  Google Scholar 

  11. Linker CA, Leavitt LJ, O'Donnell M, Forman SJ, Ries CA . Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 1991; 78: 2814–2822.

    CAS  PubMed  Google Scholar 

  12. Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: Cancer and Leukemia Group B study 8811. Blood 1995; 85: 2025–2037.

    CAS  PubMed  Google Scholar 

  13. Hoelzer D, Thiel H, Loffler H, Buchner T, Ganser A, Heil G et al. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 1988; 71: 123–131.

    CAS  PubMed  Google Scholar 

  14. Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphoblastic leukemia. J Clin Oncol 2000; 18: 547–561.

    CAS  Article  Google Scholar 

  15. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 2005; 106: 3760–3767.

    CAS  Article  Google Scholar 

  16. Thomas X, Boiron J-M, Huguet F, Dombret H, Bradstock K, Vey N et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004; 22: 4075–4086.

    CAS  Article  Google Scholar 

  17. Gokbuget N, Hoelzer D . Treatment of adult acute lymphoblastic leukemia. Am Soc Hematol Educ Program 2006; 133–141.

    Article  Google Scholar 

  18. Barry E, DeAngelo DJ, Neuberg D, Stevenson K, Loh ML, Asselin BL et al. Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana–Farber Cancer Institute acute lymphoblastic leukemia consortium protocols. J Clin Oncol 2007; 25: 813–819.

    CAS  Article  Google Scholar 

  19. Cave H, van der Werff ten Bosch J, Suciu S, Guidal C, Waterkeyn C, Otten J et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. N Engl J Med 1998; 339: 591–598.

    CAS  Article  Google Scholar 

  20. Rovera G, Wasserman R, Yamada M . Detection of minimal residual disease in childhood leukemia with the polymerase reaction. N Engl J Med 1991; 324: 774–781.

    Google Scholar 

  21. Mortuza FY, Papaioannou M, Moreira IM, Coyle LA, Gameiro P, Gandini D et al. Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol 2002; 20: 1094–1104.

    Article  Google Scholar 

  22. Bruggemann M, Raff T, Flohr T, Gokbuget N, Nakao M, Droese J et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood 2006; 107: 1116–1123.

    Article  Google Scholar 

  23. Forman SJ . Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults. In: Blume KG, Forman SJ, Appelbaum FR (eds). Thomas' Hematopoietic Cell Transplantation, 3rd edn. Blackwell Publishing Inc.: Malden, MA, 2004, pp 1055–1066.

    Google Scholar 

  24. Marks DI, Forman SJ, Blume KG, Perez WS, Weisdorf DJ, Keating A 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: 438–453.

    CAS  Article  Google Scholar 

  25. Jamieson CH, Amylon MD, Wong RM, Blume KG . Allogeneic hematopoietic cell transplantation for patients with high-risk acute lymphoblastic leukemia in first or second complete remission using fractionated total-body irradiation and high-dose etoposide: a 15-year experience. Exp Hematol 2003; 31: 981–986.

    Article  Google Scholar 

  26. Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK et al. In adults with standard-risk acute lymphoblastic leukemia (ALL) the greatest benefit is achieved from a matched sibling allogeneic transplant in first complete remission (CR) and an autologous transplant is less effective than conventional consolidation/maintenance chemotherapy in ALL patients: final results of the international ALL trial (MRC UKALL XII/ECOG E2993). Blood 2007 (Nov 29; e-pub ahead of print).

  27. Orsi C, Bartolozzi B, Messori A, Bosi A . Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation. Bone Marrow Transplant 2007; 40: 643.

    CAS  Article  Google Scholar 

  28. Snyder D, Nademanee A, O'Donnell MR, Parker PM, Stein AS, Margolin K et al. Allogeneic bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in first complete remission: long term followup. Blood 1998; 92: 657a.

    Google Scholar 

  29. Lee S, Kim YJ, Min CK, Kim HJ, Eom KS, Kim DW et al. The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 2005; 105: 3449–3457.

    CAS  Article  Google Scholar 

  30. Carpenter PA, Snyder DS, Flowers ME . Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood 2007; 109: 2791–2793.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Giona F, Testi A, Amadori G, Meloni G, Carotenuto M, Resegotti L et al. Idarubicin and high-dose cytarabine in the treatment of refractory and relapsed acute lymphoblastic leukemia. Ann Oncol 1990; 1: 51–55.

    CAS  Article  Google Scholar 

  32. Hiddemann W, Kreutzmann H, Straif K, Ludwig WD, Mertelsmann R, Planker M et al. High-dose cytosine arabinoside in combination with mitoxantrone for the treatment of refractory acute myeloid leukemia and lymphoblastic leukemia. Semin Oncol 1987; 14: 73–77.

    CAS  PubMed  Google Scholar 

  33. Cohen MH, Johnson JR, Massie T, Sridhara R, McGuinn Jr WD, Abraham S et al. Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma. Clin Cancer Res 2006; 12: 5329–5335.

    CAS  Article  Google Scholar 

  34. Specchia G, Pastore D, Carluccio P, Liso A, Mestice A, Rizzi R et al. FLAG-IDA in the treatment of refractory/relapsed adult acute lymphoblastic leukemia. Ann Hematol 2005; 84: 792–795.

    CAS  Article  Google Scholar 

  35. Doney K, Hagglund H, Leisenring W, Chauncey T, Appelbaum FR, Storb R . Predictive factors for outcome of allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2003; 9: 472–481.

    Article  Google Scholar 

  36. Bachanova V, Weisdorf D . Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant 2008; 41: 455–464.

    CAS  Article  Google Scholar 

  37. Chim CS, Lie AK, Liang R, Au WY, Kwong YL . Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor. Bone Marrow Transplant 2007; 40: 339.

    CAS  Article  Google Scholar 

  38. Coccia PF, Strandjord SE, Warkentin PI, Cheung NK, Gordon EM, Novak LJ et al. High-dose cytosine arabinoside and fractionated total-body irradiation: an improved preparative regimen for bone marrow transplantation of children with acute lymphoblastic leukemia in remission. Blood 1988; 71: 888–893.

    CAS  PubMed  Google Scholar 

  39. Champlin R, Jacobs A, Gale RP, Ho W, Selch M, Lenarsky C et al. High-dose cytarabine in consolidation chemotherapy or with bone marrow transplantation for patients with acute leukemia: preliminary results. Semin Oncol 1985; 12: 190–195.

    CAS  PubMed  Google Scholar 

  40. Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB et al. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 1983; 309: 1347–1353.

    CAS  Article  Google Scholar 

  41. Tutschka PJ, Copelan EA, Klein JP . Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood 1987; 70: 1382–1388.

    CAS  PubMed  Google Scholar 

  42. Davies SM, Ramsay NKC, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 2000; 18: 340–347.

    CAS  Article  Google Scholar 

  43. Russell JA, Savoie ML, Balogh A, Turner AR, Larratt L, Chaudhry MA et al. Allogeneic transplantation for adult acute leukemia in first and second remission with a novel regimen incorporating daily intravenous busulfan, fludarabine, 400 CGY total-body irradiation, and thymoglobulin. Biol Blood Marrow Transplant 2007; 13: 814–821.

    CAS  Article  Google Scholar 

  44. Blume KG, Forman SJ, O'Donnell MR, Doroshow JH, Krance RA, Nademanee AP et al. Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies. Blood 1987; 69: 1015–1020.

    CAS  PubMed  Google Scholar 

  45. Blume KG, Kopecky KJ, Henslee-Downey JP, Forman SJ, Stiff PJ, LeMaistre CF 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: 2187–2193.

    CAS  PubMed  Google Scholar 

  46. Matthews DC, Appelbaum FR, Eary JF, Fisher DR, Durack LD, Hui TE et al. Phase I study of 131I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome. Blood 1999; 94: 1237–1247.

    CAS  PubMed  Google Scholar 

  47. Wong JY, Liu A, Schultheiss T, Popplewell L, Stein A, Rosenthal J et al. Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation. Biol Blood Marrow Transplant 2006; 12: 306–315.

    Article  Google Scholar 

  48. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  49. Appelbaum FR . Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL). Leukemia 1997; 11: S15–S17.

    PubMed  Google Scholar 

  50. Doney K, Fisher LD, Appelbaum FR, Buckner CD, Storb R, Singer J 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: 453–459.

    CAS  PubMed  Google Scholar 

  51. Passweg JR, Tiberghien P, Cahn J-Y, Vowels MR, Camitta BM, Gale RP et al. Graft-versus-leukemia effects in T lineage and B lineage acute lymphoblastic leukemia. Bone Marrow Transplant 1998; 21: 153–158.

    CAS  Article  Google Scholar 

  52. Appelbaum FR . Hematopoietic cell transplantation as immunotherapy. Nature 2001; 411: 385–389.

    CAS  Article  Google Scholar 

  53. Mutis T, Verdijk R, Schrama E, Esendam B, Brand A, Goulmy E . Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens. Blood 1999; 94: 4374–4376.

    Google Scholar 

  54. Warren EH, Greenberg PD, Riddell SR . Cytotoxic T-lymphocyte-defined human minor histocompatibility antigens with a restricted tissue distribution. Blood 1998; 91: 2197–2207.

    CAS  PubMed  Google Scholar 

  55. Jensen MC, Clarke P, Tan G, Wright C, Chung-Chang W, Clark TN et al. Human T lymphocyte genetic modification with naked DNA. Mol Ther 2000; 1: 49–55.

    CAS  Article  Google Scholar 

  56. Cooper LJ, Topp MS, Serrano LM, Gonzalez S, Chang WC, Naranjo A et al. T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect. Blood 2003; 101: 1637–1644.

    CAS  Article  Google Scholar 

  57. Valcarcel D, Martino R, Sureda A, Canals C, Altes A, Briones J et al. Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematological malignancies. Eur J Haematol 2005; 74: 144–151.

    CAS  Article  Google Scholar 

  58. Arnold R, Massenkeil G, Bornhäuser M, Ehninger G, Beelen DW, Fauser AA et al. Nonmyeloablative stem cell transplantation in adults with high-risk ALL may be effective in early but not in advanced disease. Leukemia 2002; 16: 2423–2428.

    CAS  Article  Google Scholar 

  59. Gutierrez-Aguirre CH, Gomez-Almaguer D, Cantu-Rodriguez OG, Gonzalez-Llano O, Jaime-Perez JC, Herena-Perez S et al. Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia: results of a multicenter study. Bone Marrow Transplant 2007; 40: 535–539.

    CAS  Article  Google Scholar 

  60. Stein A, O'Donnell M, Snyder D, Parker P, Nademanee A, Falk P et al. Reduced-intensity stem cell transplantation for high-risk acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2007; 13: 134.

    Article  Google Scholar 

  61. Rowe JM, Goldstone AH . How I treat acute lymphocytic leukemia in adults. Blood 2007; 110: 2268–2275.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S J Forman.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Stein, A., Forman, S. Allogeneic transplantation for ALL in adults. Bone Marrow Transplant 41, 439–446 (2008). https://doi.org/10.1038/bmt.2008.1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.1

Keywords

  • ALL
  • transplant regimens
  • reduced-intensity transplant

Further reading

Search

Quick links