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The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921)

Abstract

This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor.

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References

  1. Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D . Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 1984; 59: 425–433.

    Article  Google Scholar 

  2. Bennett JM, Catovsky D, Daniel MD, Flandrin G, Galton DAG, Gralnick HR et al. (FAB cooperative group). Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.

    Article  CAS  PubMed  Google Scholar 

  3. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088 (erratum Blood 1998; 91: 1100).

    CAS  PubMed  Google Scholar 

  4. O'Donnell MR, Nademanee A, Snyder DS, Schmidt GM, Parker PM, Bierman PJ et al. Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes. J Clin Oncol 1987; 5: 1822–1826.

    Article  CAS  PubMed  Google Scholar 

  5. Longmore G, Guinan EC, Weinstein HJ, Gelber RD, Rappeport JM, Antin JH . Bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukaemia. J Clin Oncol 1990; 8: 1707–1714.

    Article  CAS  PubMed  Google Scholar 

  6. De Witte T, Zwaan F, Hermans J, Vernant J, Kolb H, Vossen J et al. Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukemia Working Party of the European Bone Marrow Transplantation Group (EBMTG). Br J Haematol 1990; 74: 151–155.

    Article  CAS  PubMed  Google Scholar 

  7. Sutton L, Chastang C, Ribaud P, Jouet JP, Kuentz M, Attal M, Reiffers J et al. Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients. Blood 1996; 88: 358–365.

    CAS  PubMed  Google Scholar 

  8. Nevill TJ, Shepherd JD, Reece DE, Barnett MJ, Nantel SH, Klingeman HG et al. Treatment of myelodysplastic syndrome with busulfan-cyclophosphamide conditioning followed by allogeneic BMT. Bone Marrow Transplantation 1992; 10: 445–450.

    CAS  PubMed  Google Scholar 

  9. Anderson JE, Appelbaum FR, Fisher LD, Schoch G, Shulman H, Anasetti C et al. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood 1993; 82: 677–681.

    CAS  PubMed  Google Scholar 

  10. Anderson JE, Appelbaum FR, Storb R . An update on allogeneic marrow transplantation for myelodysplastic syndrome. Leukemia Lymphoma 1995; 17: 95–99.

    Article  CAS  PubMed  Google Scholar 

  11. Anderson JE, Appelbaum FR, Schoch G, Gooley T, Anasetti C, Bensinger WI et al. Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimen and analysis of prognostic factors. Blood 1996; 87: 51–58.

    CAS  PubMed  Google Scholar 

  12. Runde V, de Witte T, Arnold R, Gratwohl A, Hermans J, van Biezen A et al. On behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Bone Marrow Transplantation 1998; 21: 255–260.

    Article  CAS  PubMed  Google Scholar 

  13. De Witte T, Muus P, De Pauw B, Haanen C . Intensive antileukemic treatment of patients younger than 65 years with myelodysplastic syndromes and secondary acute myelogenous leukaemia. Cancer 1990; 66: 831–837.

    Article  CAS  PubMed  Google Scholar 

  14. Fenaux P, Morel P, Rose C, Lai JL, Jouet JP, Bauters F . Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy. Br J Haematol 1991; 77: 497–501.

    Article  CAS  PubMed  Google Scholar 

  15. De Witte T, Suciu S, Peetermans M, Fenaux P, Strijckmans P, Hayat M et al. Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myelogenous leukaemia following MDS of more than 6 months duration A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment of Cancer (EORTC-LCG). Leukemia 1995; 9: 1805–1811.

    CAS  PubMed  Google Scholar 

  16. Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM et al. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol 1997; 99: 939–944.

    Article  CAS  PubMed  Google Scholar 

  17. Estey E, Thall P, Beran M, Kantarjian H, Pierce S, Keating M . Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukaemia [AML]) on outcome of AML-type chemotherapy. Blood 1997; 90: 2969–2977.

    CAS  PubMed  Google Scholar 

  18. Laporte JP, Isnard F, Lesage S, Fenaux P, Douay L, Lopez M et al. Autologous bone marrow transplantation with marrow purged by Mafosfamide in seven patients with myelodysplastic syndromes in transformation (AML-MDS): a pilot study. Leukemia 1993; 7: 2030–2033.

    CAS  PubMed  Google Scholar 

  19. De Witte T, Van Biezen A, Hermans J, Labopin M, Runde V, Or R et al. Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia following MDS. Blood 1997; 90: 3853–3857.

    CAS  PubMed  Google Scholar 

  20. Wattel E, Solary E, Leleu X, Dreyfus F, Brion A, Jouet JP et al. Groupe Français des Myélodysplasies (GFM) and Groupe Ouest-Est d'étude des Leucémies aiguës myéloïdes (GOELAM). A prospective study of autologous bone marrow or peripheral stem cell transplantation in myelodysplastic syndromes. Leukemia 1999; 13: 524–529.

    Article  CAS  PubMed  Google Scholar 

  21. de Witte T, Suciu S, Verhoef G, Labar B, Archimbaud E, Aul C et al. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukaemia following MDS. Blood 2001; 98: 2326–2331.

    Article  CAS  PubMed  Google Scholar 

  22. Mitelman F (ed): ISCN (1995). An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: Karger.

  23. Keating MJ, Smith TL, Kantarjian H, Cork A, Walters R, Trujillo JM et al. Cytogenetic pattern in acute myelogenous leukaemia: a major reproducible determinant of outcome. Leukemia 1988; 2: 403–412.

    CAS  PubMed  Google Scholar 

  24. Kalbfleisch JD, Prentice RL. ISCN (1990). The Statistical Analysis of Failure Time Data. New York: J Wiley.

  25. Anderson JE, Gooley TA, Schoch G, Anasetti C, Bensinger WI, Clift RA et al. Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy. Blood 1997; 89: 2578–2585.

    CAS  PubMed  Google Scholar 

  26. Suciu S . The value of BMT in AML patients in first remission, a statistician's view-point. Ann Hematol 1991; 62: 41–44.

    Article  CAS  PubMed  Google Scholar 

  27. Mattijsen V, Schattenberg A, Schaap N, Preijers F, de Witte T . Outcome of allogeneic bone marrow transplantation with lymphocyte-depleted marrow grafts in adult patients with myelodysplastic syndromes. Bone Marrow Transplantation 1997; 19: 791–794.

    Article  Google Scholar 

  28. De Witte T, Hermans J, Vossen J, Bacigalupo A, Meloni G, Jacobsen N et al. Haematopoietic stem cell transplantation for patients with myelodysplastic syndromes and secondary acute myeloid leukaemias: a report an behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2000; 110: 620–630.

    Article  CAS  PubMed  Google Scholar 

  29. Ljungman P, De Witte T, Verdonck L, Gahrton G, Freycon F, Gravett P et al. Bone marrow transplantation for acute myeloblastic leukaemia: an EBMT Leukemia Working Party prospective analysis from HLA-typing. Br J Haematol 1993; 84: 61–66.

    Article  CAS  PubMed  Google Scholar 

  30. Keating S, De Witte T, Suciu S, Willemze R, Hayat M, Labar B et al. The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukemia Cooperative Group and GIMEMA. Br J Haematol 1998; 102: 1344–1353.

    Article  CAS  PubMed  Google Scholar 

  31. Gray R, Wheatley K . How to avoid bias when comparing bone marrow transplantation with chemotherapy. Bone Marrow Transplantation 1991; 7: 9–12.

    PubMed  Google Scholar 

  32. Archimbaud E, Thomas X, Michallet M, Jauber J, Troncy J, Guyotat D et al. Prospective genetically randomized comparison between intensive postinduction chemotherapy and marrow transplantation in adults with newly diagnosed acute myeloid leukemia. J Clin Oncol 1994; 12: 262–267.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The work was supported in part by a grant of the National Cancer Institute (Grant nos 2U10-CA11488-22 to 2U10-CA11488-31). Its contents are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute. We acknowledge Saint Jude Children's Research Hospital for providing a SAS macro allowing the analyses of competing risks.

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University Medical Centre Nijmegen, Nijmegen (T de Witte); Brussels U.Z. Gasthuisberg, Leuven (G Verhoef); University Hospital Rebro, Zagreb (B Labar); Hôpital Edouard Herriot, Lyon (A Belhabri); Leijenburg Ziekenhuis, The Hague (P Wijermans); Universitaetsklinikum Essen, Essen (V Runde); St Jan's Hospital, Brugge (D Selleslag); Leiden University Medical Centre (R Willemze); Kantonsspital Basel, Basel (A Gratwohl); Universita La Sapienza, Roma (F Mandelli); Cliniques Universitaires St Luc, Brussels (A Ferrant); Hôpital Dieu, Paris (R Zittoun); Klinikum Grosshadern Ludwig-Maximilians University, Munich (U Jehn); Universitair Ziekenhuis Antwerpen, Antwerpen (Z Berneman); Hopital Universitaire Erasme, Brussels (W Feremans); Inselspital, Bern (M Fey); Ospedale San Eugenio, Roma (S Amadori); Academisch Medisch Centrum, Amsterdam (J van der Lelie); Institut J Bordet, Brussels (P Strijckmans); Cliniques Universitaires de Mont Godinne, Yvoir (A Bosly); Centre Antoine Lacassagne, Nice (A Thyss); Onze Lieve Vrouwen gasthuis, Amsterdam (KJ Roozendaal); Atrium Medisch Centrum, Heerlen (M Fickers); Hospital de la Santa Creu I Sant Pau (Barcelona); Academisch Ziekenhuis Maastricht (H Schouten); Klinikum Nurnberg, Nurnberg (H Wandt); Innsbruck Universitaetsklinikum, Innsbruck (H Zwierzina); Jeroen Bosch Ziekenhuis, ‘s Hertogenbosch (H Sinnege); St Josef Ziekenhuis, Veldhoven (G Vreugdenhil); Algemeen Ziekenhuis Middelheim, Antwerpen (R de Bock); CHU Sart-Tilman, Liège (G Fillet); Kantonsspital Sankt Gallen, Sankt Gallen (U Hess); Heinrich Heine University, Dusseldorf (C Aul); Ospedale San Giovanni, Bellinzona (F Cavelli); Institute of Hematology and Blood Transfusion, Prague (J Cermak); Instituto Portugues de Oncologia-Centro de Coimbra, Coimbra (I Sousa).

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Oosterveld, M., Suciu, S., Verhoef, G. et al. The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921). Leukemia 17, 859–868 (2003). https://doi.org/10.1038/sj.leu.2402897

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