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Comparable outcome after single-antigen-mismatched versus matched unrelated donor haematopoietic cell transplantation

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

Allogeneic haematopoietic stem cell transplantation (HSCT) is a proven treatment for patients with haematological malignancies. In this retrospective analysis, the impact of donor matching on outcome of unrelated HSCT was analysed in patients transplanted at the University of Leipzig.

Methods

From 2000 to 2009, 206 patients were transplanted from unrelated donors, of which 51 were mismatched (39 in 1 and 12 in ≥2 HLA-antigens), using peripheral blood or bone marrow grafts after total body irradiation and cyclophosphamide or busulfan and cyclophosphamide preparative regimens in combination with ATG. For graft-versus-host disease (GvHD) prophylaxis cyclosporine and MTX were administered.

Results

After a median follow-up of 49 months, outcome at 5 years in recipients of HLA-identical grafts was comparable to that of patients transplanted from HLA-incompatible donors with an overall survival (OS) of 52 % (95 % CI 43–61) versus 48 % (95 % CI 34–63), respectively (p = 0.48). Results were also comparable for event-free survival at 5 years [47 % (95 % CI 38–56) vs. 39 % (95 % CI 25–54); p = 0.44], relapse incidence (RI) [29 % (95 % CI 20–38) vs. 41 (95 % CI 25–57); p = 0.22] and non-relapse mortality [24 % (95 % CI 16–33) vs. 20 % (95 % CI 8–33); p = 0.84] in the matched versus mismatched groups. Incidence of acute and chronic GvHD was similar in both groups. Advanced disease (p = 0.02) and low-resolution typing (p = 0.04) are risk factors for OS and RI in univariate and multivariate analysis.

Conclusions

Donors with one antigen mismatch are an acceptable option for patients with malignant disease for whom no fully matched donor is available.

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References

  • Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD et al (1989) Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med 320(4):197–204

    Article  CAS  PubMed  Google Scholar 

  • Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S et al (2005) Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 23(15):3447–3454

    Article  PubMed  Google Scholar 

  • Ballen KK, Spitzer TR, Yeap BY, McAfee S, Dey BR, Attar E et al (2007) Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Biol Blood Marrow Transpl 13(1):82–89

    Article  CAS  Google Scholar 

  • Barker JN, Davies SM, DeFor T, Ramsay NK, Weisdorf DJ, Wagner JE (2001) 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 97(10):2957–2961

    Article  CAS  PubMed  Google Scholar 

  • Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE (2003) Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 102(5):1915–1919

    Article  CAS  PubMed  Google Scholar 

  • Basara N, Baurmann H, Kolbe K, Yaman A, Labopin M, Burchardt A et al (2005) Antithymocyte globulin for the prevention of graft-versus-host disease after unrelated hematopoietic stem cell transplantation for acute myeloid leukemia: results from the multicenter German cooperative study group. Bone Marrow Transpl 35(10):1011–1018

    Article  CAS  Google Scholar 

  • Beatty P, Dahlberg S, Mickelson EM, Nisperos B, Opelz G, Martin P et al (1988) Probability of finding HLA-matched unrelated marrow donors. Transplantation 45:714–718

    Article  CAS  PubMed  Google Scholar 

  • Beatty PG, Anasetti C, Hansen JA, Longton GM, Sanders JE, Martin PJ et al (1993) Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus. Blood 81(1):249–253

    CAS  PubMed  Google Scholar 

  • Copelan EA, Biggs JC, Thompson JM, Crilley P, Szer J, Klein JP et al (1991) Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2. Blood 78:838–843

    CAS  PubMed  Google Scholar 

  • Feinstein LC, Sandmaier BM, Hegenbart U, McSweeney PA, Maloney DG, Gooley TA et al (2003) Non-myeloablative allogafting from human leucocyte antigen-identical sibling donors for treatment of acute myeloid leukaemia in first complete remission. Br J Haematol 120:281–288

    Article  PubMed  Google Scholar 

  • Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94(446):496–509

    Article  Google Scholar 

  • Finke JÃ, Schmoor C, Lang H, Potthoff K, Bertz H (2003) Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin. J Clin Oncol 21(3):506–513

    Article  PubMed  Google Scholar 

  • Flomenberg N, Baxter-Lowe LA, Confer D, Fernandez-Vina M, Filipovich A, Horowitz M et al (2004) 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 104(7):1923–1930

    Article  CAS  PubMed  Google Scholar 

  • Goodrich JM, Mori M, Gleaves CA, Du Mond C, Cays M, Ebeling DF et al (1991) Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med 325(23):1601–1607

    Article  CAS  PubMed  Google Scholar 

  • Gooley TA1, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18(6):695–706

    Article  CAS  PubMed  Google Scholar 

  • Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M et al (2010) Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 363(22):2091–2101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gratwohl A, Hermans J, Goldman J, Arcese W, Carreras E, Devergie A et al (1998) Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Lancet 352:1087–1092

    Article  CAS  PubMed  Google Scholar 

  • Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, De Witte T et al (2009) Risk score for outcome after allogeneic hematopoietic stem cell transplantation. Cancer 115(20):4715–4726

    Article  PubMed  Google Scholar 

  • Gratwohl A, Brand R, Niederwieser D, Baldomero H, Chabannon C, Cornelissen J et al (2011) Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation. J Clin Oncol 29(15):1980–1986

    Article  PubMed  Google Scholar 

  • Gray RJ (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16(3):1441–1454

    Article  Google Scholar 

  • Greinix HT, Faé I, Schneider B, Rosenmayr A, Mitterschiffthaler A, Pelzmann B et al (2005) Impact of HLA class I high-resolution mismatches on chronic graft-versus-host disease and survival of patients given hematopoietic stem cell grafts from unrelated donors. Bone Marrow Transpl 35(1):57–62

    Article  CAS  Google Scholar 

  • Kanda J, Saji H, Fukuda T, Kobayashi T, Miyamura K, Eto T et al (2012) Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study. Blood 119(10):2409–2416

    Article  CAS  PubMed  Google Scholar 

  • Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  • Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A et al (1993) Analysis of 462 transplantations from unrelated donors facilitated by the national marrow donor program. N Engl J Med 328:593–602

    Article  CAS  PubMed  Google Scholar 

  • Kroeger N, Zabelina T, Binder T, Ayuk F, Bacher U, Amtsfeld G et al (2009) HLA-mismatched unrelated donors as an alternative graft source for allogeneic stem cell transplantation after antithymocyte globulin-containing conditioning regimen. Biol Blood Marrow Transpl 15(4):454–462

    Article  CAS  Google Scholar 

  • Kroger N, Zabelina T, Kruger W, Renges H, Stute N, Durken M et al (2001) Anti-thymocyte-globulin as part of the preparative regimen prevents graft failure and severe graft versus host disease (GvHD) in allogeneic stem cell transplantation from unrelated donors. Ann Hematol 80(4):209–215

    Article  CAS  PubMed  Google Scholar 

  • la Porta MG, Malcovati L, Strupp C, Ambaglio I, Kuendgen A, Zipperer E et al (2011) Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica 96(3):441–449

    Article  PubMed Central  PubMed  Google Scholar 

  • Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE et al (2001) Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 344(24):1815–1822

    Article  CAS  PubMed  Google Scholar 

  • Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M et al (2007) High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 110(13):4576–4583

    Article  CAS  PubMed  Google Scholar 

  • Ljungman P, Urbano Ispizua A, Cavazzani-Calvo M, Demirer T, Dini G, Einsele H et al (2006) Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe. Bone Marrow Transpl 37:439–449

    Article  CAS  Google Scholar 

  • Loiseau P, Busson M, Balere ML, Dormoy A, Bignon JD, Gagne K et al (2007) HLA association with hematopoietic stem cell transplantation outcome: the number of mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 is strongly associated with overall survival. Biol Blood Marrow Transpl 13(8):965–974

    Article  CAS  Google Scholar 

  • Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W et al (2006) Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 107(8):3065–3073

    Article  CAS  PubMed  Google Scholar 

  • Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50(3):163–170

    CAS  PubMed  Google Scholar 

  • Maris MB, Niederwieser D, Sandmaier BM, Storer B, Stuart M, Maloney D et al (2003) HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 102(6):2021–2030

    Article  CAS  PubMed  Google Scholar 

  • McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina A-J, Maloney DG et al (2001) Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 1(97):3390–3400

    Article  Google Scholar 

  • Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K et al (2002) The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood 99(11):4200–4206

    Article  CAS  PubMed  Google Scholar 

  • Nademanee A, Schmidt GM, Parker P, Dagis AC, Stein A, Snyder DS et al (1995) The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease prophylaxis regimen of cyclosporine, methotrexate, and prednisone. Blood 86(3):1228–1234

    CAS  PubMed  Google Scholar 

  • National Marrow Donor Program (1992) Donor center manual of operations. Minneapolis, Chapter 6 (p 11)

  • Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier B et al (2003) Low-dose total body irradiation (TBI) and fludarabine follwed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 101(4):1620–1629

    Article  CAS  PubMed  Google Scholar 

  • Petersdorf EW, Kollman C, Hurley CK, Dupont B, Nademanee A, Begovich AB et al (2001a) Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program Experience. Blood 98(10):2922–2929

    Article  CAS  PubMed  Google Scholar 

  • Petersdorf EW, Hansen JA, Martin PJ, Woolfrey A, Malkki M, Gooley T et al (2001b) Major-histocompatibility-complex class I alleles and antigens in hematopoetic-cell transplantation. N Engl J Med 345(25):1794–1800

    Article  CAS  PubMed  Google Scholar 

  • Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al (1995) 1994 Consensus conference on acute GVHD grading. Bone Marrow Transpl 15(6):825–828

    CAS  Google Scholar 

  • Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H et al (1998) Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. N Engl J Med 339(17):1177–1185

    Article  CAS  PubMed  Google Scholar 

  • Scott BL, Gooley TA, Sorror ML, Rezvani AR, Linenberger ML, Grim J et al (2012) The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood 119(11):2657–2664

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shaw BE, Madrigal JA, Potter M (2001) Improving the outcome of unrelated donor stem cell transplantation by molecular matching. Blood Rev 15(4):167–174

    Article  CAS  PubMed  Google Scholar 

  • Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al (1980) chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 seattle patients. Am J Med 69:204–217

    Article  CAS  PubMed  Google Scholar 

  • Slavin MA1, Osborne B, Adams R, Levenstein MJ, Schoch HG, Feldman AR et al (1995) Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation—a prospective, randomized, double-blind study. J Infect Dis 171(6):1545–1552

    Article  CAS  PubMed  Google Scholar 

  • Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106(8):2912–2919

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sorror ML, Sandmaier BM, Storer BE, Maris MB, Baron F, Maloney DG et al (2007) Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 25(27):4246–4254

    Article  PubMed  Google Scholar 

  • Storb R, Deeg HJ, Pepe M, Appelbaum FR, Anasetti C, Beatty P et al (1989) Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial. Blood 73:1729–1734

    CAS  PubMed  Google Scholar 

  • Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C et al (2008) Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival. Biol Blood Marrow Transpl 14(7):748–758

    Article  Google Scholar 

  • Woolfrey A, Klein JP, Haagenson M, Spellman S, Petersdorf E, Oudshoorn M et al (2011) HLA-C antigen mismatch is associated with worse outcome in unrelated donor peripheral blood stem cell transplantation. Biol Blood Marrow Transpl 17(6):885–892

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology, University Hospital Leipzig, 04103, Leipzig, Germany

    A. Rockstroh, H. K. Al-Ali, T. Lange, W. Pönisch, R. Krahl, M. Cross, G. Behre, D. Niederwieser & C. Pfrepper

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  1. A. Rockstroh
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  2. H. K. Al-Ali
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  3. T. Lange
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  4. W. Pönisch
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  5. R. Krahl
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  6. M. Cross
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  7. G. Behre
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  8. D. Niederwieser
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  9. C. Pfrepper
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Correspondence to C. Pfrepper.

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Informed consent was obtained from all individual patients included in this study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Rockstroh, A., Al-Ali, H.K., Lange, T. et al. Comparable outcome after single-antigen-mismatched versus matched unrelated donor haematopoietic cell transplantation. J Cancer Res Clin Oncol 141, 2193–2203 (2015). https://doi.org/10.1007/s00432-015-2003-5

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  • DOI: https://doi.org/10.1007/s00432-015-2003-5

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