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Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review

Bone Marrow Transplantation volume 41, pages 455–464 (2008)Cite this article

Abstract

Acute lymphoblastic leukemia is highly sensitive to induction chemotherapy; however, long-term survival in adults has been less than 35%, primarily as a result of high relapse rate. Treatment for relapsed disease is even less successful. The optimal post-remission therapy in the first complete remission offers the best opportunity for leukemia-free survival. Allogeneic donor stem cell transplantation can offer a unique anti-leukemia effect and a potential for extended survival. We will discuss advances in unrelated donor (URD) stem cells transplantation, improvements in transplantation process and supportive care along with growing experience with umbilical cord blood (UCB) allografts.

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References

  1. Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant 2006; 12: 1–30.

    Article  CAS  Google Scholar 

  2. Thomas X, Boiron JM, 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.

    Article  CAS  Google Scholar 

  3. Thiebaut A, Vernanr JP, Degos L, Huguet FR, Reiffers J, Debban C et al. Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation. A follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am 2000; 14: 1353–1365.

    Article  CAS  Google Scholar 

  4. Dombret H, Gabert J, Boiron JM, Rigal-Huguet F, Blaise B, Thomas X et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia—results of the prospective multicenter LALA-94 trial. Blood 2002; 100: 2357–2366.

    Article  CAS  Google Scholar 

  5. Labar B, Suciu S, Zittoun R, Muus P, Marie JP, Fillet G, et al., EORTC Leukemia Group. Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients <or=50 years old in first complete remission: results of the EORTC ALL-3 trial. Haematologica 2004; 89: 809–817.

    PubMed  Google Scholar 

  6. Ringden O, Labopin M, Bacigalupo A, Arcese W, Schaefer UW, Willemze R et al. Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia. J Clin Oncol 2002; 20: 4655–4664.

    Article  CAS  Google Scholar 

  7. Attal M, Blaise D, Marit G, Payen C, Michallet M, Vernant JP et al. Consolidation treatment of adult acute lymphoblastic leukemia: a prospective, randomized trial comparing allogeneic versus autologous bone marrow transplantation and testing the impact of recombinant interleukin-2 after autologous bone marrow transplantation. BGMT Group. Blood 1995; 86: 1619–1628.

    CAS  PubMed  Google Scholar 

  8. Ribera JM, Oriol A, Bethencourt C, Parody R, Hernandez-Rivas JM, Moreno MJ et al. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica 2005; 90: 1346–1356.

    CAS  PubMed  Google Scholar 

  9. Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S et al. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia 2002; 16: 1259–1266.

    Article  CAS  Google Scholar 

  10. Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F, et al., GOELAMS (Groupe Ouest-Est des Leucemies Airgues et Maladies du Sang) Group. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 2004; 104: 3028–3037.

    Article  CAS  Google Scholar 

  11. Gupta V, Yi QL, Brandwein J, Minden MD, Schuh AC, Wells RA et al. The role of allogeneic bone marrow transplantation in adult patients below the age of 55 years with acute lymphoblastic leukemia in first complete remission: a donor vs no donor comparison. Bone Marrow Transplant 2004; 33: 397–404.

    Article  CAS  Google Scholar 

  12. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM et al. Induction therapy for adults with acute lymphoblastic leukemia (ALL): results of over 1500 patients from the International ALL Trial (MRC UKALL/ECOG 2993). Blood 2005; 106: 3760–3767.

    Article  CAS  Google Scholar 

  13. Yanada M, Metsue K, Takeshi S, Tomoki N . Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia. A meta-analysis. Cancer 2006; 106: 2657–2663.

    Article  Google Scholar 

  14. Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL): an MRC UKALL12/ECOG 2993 study. Blood 2007; 109: 944–950.

    Article  CAS  Google Scholar 

  15. Weisdorf D, Bishop M, Dharan B, Bolwell B, Cahn JY, Cairo M et al. Autologous versus allogeneic unrelated donor transplantation for acute lymphoblastic leukemia: comparative toxicity and outcomes. Biol Blood Marrow Transplant 2002; 8: 213–220.

    Article  Google Scholar 

  16. Center of International Blood and Marrow Transplant Research 2006. Newsletter 2006; 12: 8 (www.cibmtr.org).

  17. Sierra J, Radich J, Hansen JA, Martin PJ, Petersdorf EW, Bjerke J et al. Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 1997; 90: 1410–1414.

    CAS  PubMed  Google Scholar 

  18. Marks DI, Bird JM, Cornish JM, Goulden NJ, Jones CG, Knechtli CJ et al. Unrelated donor bone marrow transplantation for children and adolescents with Philadelphia-positive acute lymphoblastic leukemia. J Clin Oncol 1998; 16: 931–936.

    Article  CAS  Google Scholar 

  19. Talano JM, Casper JT, Camitta BM, Keever-Taylor CA, Murray KJ, Eapen M et al. Alternative donor bone marrow transplant for children with Philadelphia chromosome ALL. Bone Marrow Transplant 2006; 37: 135–141.

    Article  CAS  Google Scholar 

  20. de Labarthe A, Rousselot P, Huguet-Rigal F, Delabesse E, Witz F, Maury S et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 2007; 109: 1408–1413.

    Article  CAS  Google Scholar 

  21. Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a Phase II study. Blood 2007; 110: 2309–2315.

    Article  CAS  Google Scholar 

  22. Garderet L, Labopin M, Gorin NC, Polge E, Fouillard L, Ehringer GE et al. Patients with acute lymphoblastic leukemia allografted with a matched unrelated donor may have a lower survival with a peripheral blood stem cell graft compared to bone marrow. Bone Marrow Transplant 2003; 31: 23–29.

    Article  CAS  Google Scholar 

  23. Kiehl MG, Kraut L, Schwerdtfeger R, Hertenstein B, Remberger M, Kroeger N et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission. J Clin Oncol 2004; 22: 2816–2825.

    Article  Google Scholar 

  24. Cornelissen JJ, Carston M, Kollman C, King R, Dekker AW, Lowenberg B 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: 1572–1577.

    Article  CAS  Google Scholar 

  25. Dahlke J, Kröger N, Zabelina T, Ayuk F, Fehse N, Wolschke C et al. Comparable results in patients with acute lymphoblastic leukemia after related and unrelated stem cell transplantation. Bone Marrow Transplant 2006; 37: 155–163.

    Article  CAS  Google Scholar 

  26. Ringden O, Labopin M, Tura S, Arcese W, Iriondo A, Zittoun R et al. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 1996; 93: 637–645.

    Article  CAS  Google Scholar 

  27. Marks DI, Forman SJ, Blume KG, Pérez 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: 293–300.

    Article  Google Scholar 

  28. 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.

    Article  CAS  Google Scholar 

  29. Martino R, Giralt S, Caballero MD, Mackinnon S, Corradini P, Fernández-Avilés F et al. Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning in acute lymphoblastic leukemia: a feasibility study. Haematologica 2003; 88: 555–560.

    PubMed  Google Scholar 

  30. Bacigalupo A, Lambarelli T, Ciceri F, Peccatori F, Locasciulli A, Majolino I et al. A randomized trial of rabbit anti-thymocyte globulin, given on day+7 after alternative donor transplants. Blood 2006; ASH Annual Meeting Abstract 106: 754.

  31. Cutler C, Li S, Ho V, Koreth J, Alyea E, Soiffer RJ et al. Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation. Blood 2007; 109: 3108–3114.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 2005; 105: 1343–1347.

    Article  CAS  Google Scholar 

  33. Bunin N, Aplenc R, Kamani N, Shaw K, Cnaan A, Simms S . Randomized trial of busulfan vs. total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant 2003; 32: 543–548.

    Article  CAS  Google Scholar 

  34. Massenkeil G, Nagy M, Neuburger S, Tamm I, Lutz C, et al. Survival after reduced-intensity conditioning is not inferior to standard high-dose conditioning before allogeneic haematopoietic cell transplantation in acute leukemias. Bone Marrow Transplantation 2005; 36: 683–689.

    Article  CAS  Google Scholar 

  35. Hamaki T, Kami M, Kanda Y, Yuji K, Inamoto Y, Kishi Y et al. Reduced intensity stem-cell transplantation for acute lymphoblastic leukemia: a retrospective study of 33 patients. Bone Marrow Tranplant 2005; 35: 549–556.

    Article  CAS  Google Scholar 

  36. Barker JN, Davies SM, DeFor T, Ramsay NK, Weisdorf DJ, Wagner JE . Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Blood 2001; 97: 2957–2961.

    Article  CAS  Google Scholar 

  37. Lekakis L, Giralt S, Couriel D, Shpall EJ, Hosing C, Khouri IF et al. Phase II study of unrelated cord blood transplantation for adults with high-risk hematologic malignancies. Bone Marrow Transplant 2006; 38: 421–426.

    Article  CAS  Google Scholar 

  38. Hahn T, Bunworasate U, George MC, Bir AS, Chinratanalab W, Alam AR et al. Use of non-volume reduced (unmanipulated after thawing) umbilical cord blood stem cells for allogeneic transplantation results in safe engraftment. Bone Marrow Transplant 2003; 32: 145–150.

    Article  CAS  Google Scholar 

  39. Cornetta K, Laughlin M, Carter S, Wall D, Weinthal J, Delaney C et al. Umbilical cord blood transplantation in adults: results of the prospective cord blood transplantation (COBLT). Biol Blood Marrow Transplant 2005; 11: 149–160.

    Article  Google Scholar 

  40. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.

    Article  CAS  Google Scholar 

  41. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.

    Article  CAS  Google Scholar 

  42. Takahashi S, Iseki T, Ooi J, Tomonari A, Takasugi K, Shimohakamada Y et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood 2004; 104: 3813–3820.

    Article  CAS  Google Scholar 

  43. Kumar P, Defor TE, Brunstein C, Barker J, Wagner JE, Weisdorf DJ et al. Allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of acute lymphocytic leukemia (ALL) in 126 adults: impact of donor source on leukemia free survival. Blood 2005; ASH Annual Meeting Abstracts 106: 2064.

  44. Hwang WY, Samuel M, Tan D, Koh LP, Lim W, Linn YC . A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplan 2007; 13: 444–453.

    Article  Google Scholar 

  45. Tomblyn MB, DeFor TE, Tomblyn MR, MacMillan M, Higgins PD, Dusenbery KE et al. Hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL): 25-year experience at the University of Minnesota. ASCO 2007; Abstract ID: 7001.

  46. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.

    CAS  PubMed  Google Scholar 

  47. Barker JN, Weisdorf D, Wagner JE . Creation of a double chimera after the transplantation of umbilical-cord blood from two partially matched unrelated donors. N Engl J Med 2001; 24: 1870–1881.

    Article  Google Scholar 

  48. Verneris MR, Brunstein CG, DeFor T, Barker J, Weisdorf DJ, Blazar BR et al. Risk of relapse after umbilical cord blood transplantation in patients with acute leukemia: marked reduction in recipients of two units. Blood 2005; ASH Annual Meeting Abstracts 106:305.

  49. Barker JN, Scaradavou A, Stevens CE, Rubinstein P . Analysis of 608 umbilical cord blood (UCB) transplants: HLA-match is a critical determinant of transplant-related mortality (TRM) in the post-engraftment period even in the absence of acute graft-vs-host disease (aGVHD). Blood 2005; ASH Annual Meeting Abstracts 106: 303.

  50. Yoo KH, Kang HJ, Lee SH, Jung HL, Sung KW, Koo HH et al. Double unit cord blood transplantation in children with acute leukemia. Blood 2005; ASH Annual Meeting Abstracts 106: 2043.

  51. Ballen KK, Spitzer TR, Yeap B, Steve M, Dey BR, Attar E et al. Excellent disease free survival after double cord blood transplantation using a reduced intensity chemotherapy only conditioning regimen in a diverse adult population. Blood 2005; ASH Annual Meeting Abstracts 106: 2048.

  52. Brunstein CG, Barker J, DeFor T, French K, Weisdorf DJ, Wagner JE . Non-myeloablative umbilical cord transplantation: promising disease-free survival in 95 consecutive patients. Blood 2005; ASH Annual Meeting Abstract 106:559.

  53. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE . Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.

    Article  CAS  Google Scholar 

  54. Majhail SN, Brunstein CG, Wagner JE . Double umbilical cord blood transplantation. Curr Opin Immunol 2006; 18: 571–575.

    Article  CAS  Google Scholar 

  55. Flomenberg N, Baxter-Lowe LA, Confer D, Fernandez-Vina M, Filipovich A, Horowitz M et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood 2004; 104: 1923–1930.

    Article  CAS  Google Scholar 

  56. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M et al. High resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood; e-pub ahead of print 4 September 2007.

  57. http://www.marrow.org/ABOUT/Publications/2004_Biennial_Report/PDF/biennial_report_2004.pdf.

  58. Hahn T, Bunworasate U, George MC, Bir AS, Chinratanalab W, Alam AR et al. Use of nonvolume-reduced (unmanipulated after thawing) umbilical cord stem cells for allogeneic transplantation results in safe engraftment. Bone Marrow Transplant 2003; 34: 145–150.

    Article  Google Scholar 

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  1. Department of Medicine, University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA

    V Bachanova & D Weisdorf

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Bachanova, V., Weisdorf, D. Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant 41, 455–464 (2008). https://doi.org/10.1038/sj.bmt.1705889

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