Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC

Abstract

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgments

We wish to thank all investigators and data managers. We thank all staff involved in patient care for their dedication, and we especially thank the patients who took part.

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A.L.B. and P.C. designed, performed, and coordinated the research; analyzed and interpreted the data; and wrote the manuscript. M.L. performed the statistical analyses and provided the figures. F.S., R.P.d.L., D.B., S.C., S.N.G., N.M., R.T., I.Y.A., A.H., T.M., K.B., P.C., A.C., P.T., M.T.R., T.G., and M.M. contributed data and commented on the manuscript.

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Correspondence to Amandine Le Bourgeois or Patrice Chevallier.

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All patients gave informed consent for collection of their personal data in the PROMISE data base.

The study has been approved by the ethics committee of the STGM-TC.

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Le Bourgeois, A., Labopin, M., Marçais, A. et al. Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC. Ann Hematol 99, 1855–1862 (2020). https://doi.org/10.1007/s00277-020-04074-7

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Keywords

  • Allogeneic stem cell transplantation
  • Clofarabine
  • Sequential regimen
  • Reduced intensity conditioning regimen
  • Acute myeloid leukemia