The role of stem cell source in autologous hematopoietic stem cell transplantation for patients with myelodysplastic syndromes.

BACKGROUND AND OBJECTIVES Intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) is a curative treatment option for patients with myelodysplastic syndromes (MDS). Peripheral blood (PB) HSCT was introduced in 1992 and PB has become the source of choice of autologous stem cells worldwide. Autologous PB stem cells result in faster hematopoietic recovery, but may be associated with a higher risk of relapse. DESIGN AND METHODS We analyzed the data of 336 patients transplanted after 1992 with either bone marrow (BM) (n=104) or PB (n=232). RESULTS Various factors had an impact on event-free survival in univariate analysis: age hazard ratio [HR]=1.1 per 10 years; p=0.12), source of stem cells (HR=1.2, p=0.22), interval between diagnosis and transplantation (HR=1.0 per month; p=0.87), and therapy-related vs primary disease (HR=0.5; p=0.002). In the multivariate Cox model, the event-free survival was not different after PB or BM HSCT with a HR of 0.93 (95% confidence interval of 0.67 - 1.30; p=0.67). The relapse risk after transplantation with stem cells from either source was similar with a HR of 1.1. A significant interaction (p=0.02) between age and the source of stem cells indicated a more favorable potential of autologous PB HSCT in young age groups. INTERPRETATION AND CONCLUSIONS Autologous PB and BM HSCT result in equivalent outcomes. Therefore, given the more rapid hematopoietic recovery PB is the preferred source of stem cells.

[1]  B. Horisberger,et al.  Change in stem cell source for hematopoietic stem cell transplantation (HSCT) in Europe: a report of the EBMT activity survey 2003 , 2005, Bone Marrow Transplantation.

[2]  H. Deeg,et al.  NOD/SCID mice transplanted with marrow from patients with myelodysplastic syndrome (MDS) show long-term propagation of normal but not clonal human precursors. , 2003, Leukemia research.

[3]  E. Estey,et al.  Chemotherapy only compared to chemotherapy followed by transplantation in high risk myelodysplastic syndrome and secondary acute myeloid leukemia; two parallel studies adjusted for various prognostic factors , 2002, Leukemia.

[4]  A. Hagemeijer,et al.  Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. , 2001, Blood.

[5]  G. Meloni,et al.  Haematopoietic stem cell transplantation for patients with myelo‐dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) , 2000, British journal of haematology.

[6]  T. Dewitte.  Stem cell transplantation in myelodysplastic syndromes. , 1999 .

[7]  F. Mandelli,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 Leukaemia Cooperative Group and GIMEMA , 1998, British journal of haematology.

[8]  M. Labopin,et al.  Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome , 1998, Bone Marrow Transplantation.

[9]  B. Czepulkowski,et al.  Fludarabine, cytarabine, G‐CSF and idarubicin (FLAG‐IDA) for the treatment of poor‐risk myelodysplastic syndromes and acute myeloid leukaemia , 1997, British journal of haematology.

[10]  M. Labopin,et al.  Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS , 1997 .

[11]  P. Thall,et al.  Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia [AML]) on outcome of AML-type chemotherapy. , 1997, Blood.

[12]  F. Preijers,et al.  Outcome of allogeneic bone marrow transplantation with lymphocyte-depleted marrow grafts in adult patients with myelodysplastic syndromes , 1997, Bone Marrow Transplantation.

[13]  R. Storb,et al.  Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy. , 1997, Blood.

[14]  T Hamblin,et al.  International scoring system for evaluating prognosis in myelodysplastic syndromes. , 1997, Blood.

[15]  F. Benvenuto,et al.  IN VIVO MOBILIZATION OF KARYOTyPICALLY NORMAL PERIPHERAL BLOOD PROGENITOR CELLS IN HIGH‐RISK MDS, SECONDARY OR THERAPY‐RELATED ACUTE MYELOGENOUS LEUKAEMIA , 1996, British journal of haematology.

[16]  Marie-Cécile Michallet,et al.  Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Societe Francaise de Greffe de Moelle , 1996 .

[17]  G. Verhoef,et al.  Feasibility of peripheral blood progenitor cell harvest and transplantation in patients with poor‐risk myelodysplastic syndromes , 1996, British journal of haematology.

[18]  K. Sullivan,et al.  Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors. , 1996, Blood.

[19]  G. Verhoef,et al.  Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes. , 1995, Blood.

[20]  H. Zwierzina,et al.  Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG). , 1995, Leukemia.

[21]  P. Fenaux,et al.  Autologous bone marrow transplantation with marrow purged by mafosfamide in seven patients with myelodysplastic syndromes in transformation (AML-MDS): a pilot study. , 1993, Leukemia.

[22]  F. Appelbaum,et al.  Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. , 1993, Blood.

[23]  G. Gahrton,et al.  Bone marrow transplantation for acute myeloblastic leukaemia: an EBMT Leukaemia Working Party prospective analysis from HLA‐typing , 1993, British journal of haematology.

[24]  D. Reece,et al.  Treatment of myelodysplastic syndrome with busulfan-cyclophosphamide conditioning followed by allogeneic BMT. , 1992, Bone marrow transplantation.

[25]  P. Morel,et al.  Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy , 1991, British journal of haematology.

[26]  R. Gelber,et al.  Bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukemia. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  C. Haanen,et al.  Intensive antileukemic treatment of patients younger than 65 years with myelodysplastic syndromes and secondary acute myelogenous leukemia , 1990, Cancer.

[28]  A. Gratwohl,et al.  Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG) , 1990, British journal of haematology.

[29]  P. Bierman,et al.  Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes. , 1987, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  D. Machin,et al.  Myelodysplastic syndromes: a scoring system with prognostic significance , 1985, British journal of haematology.

[31]  H. Gralnick,et al.  Proposals for the classification of the myelodysplastic syndromes , 1982, British journal of haematology.