Haematologica (Oct 2012)

Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study

  • Birgit Federmann,
  • Martin Bornhauser,
  • Christoph Meisner,
  • Lambros Kordelas,
  • Dietrich W. Beelen,
  • Gernot Stuhler,
  • Matthias Stelljes,
  • Rainer Schwerdtfeger,
  • Maximilian Christopeit,
  • Gerhard Behre,
  • Christoph Faul,
  • Wichard Vogel,
  • Michael Schumm,
  • Rupert Handgretinger,
  • Lothar Kanz,
  • Wolfgang A. Bethge

DOI
https://doi.org/10.3324/haematol.2011.059378
Journal volume & issue
Vol. 97, no. 10

Abstract

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Background We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3.Design and Methods Sixty-one adults with a median age of 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic myeloid leukemia (n=3), chronic lymphatic leukemia (n=1) and myelodysplastic syndrome (n=1). Patients were considered high risk because of refractory disease (n=18), cytogenetics (n=6), complete remission (≥2) (n=9), chemosensitive relapse in partial remission (n=4) or relapse after prior hematopoietic stem cell transplantation (n=15 allogeneic, n=8 autologous, n=1 both). At haploidentical hematopoietic stem cell transplantation, 30 patients were in complete remission and 31 in partial remission. Grafts contained a median of 7.0×106 (range 3.2-22) CD34+ cells/kg, 4.2×104 (range 0.6-44) CD3+ T cells/kg and 2.7×107 (range 0.00-37.3) CD56+ cells/kg.Results Engraftment was rapid with a median of 12 days to granulocytes more than 0.5×109/L (range 9-50 days) and 11 days to platelets more than 20×109 (range 7-38 days). Incidence of grade IIIV acute graft-versus-host-disease and chronic graft-versus-host-disease was 46% and 18%, respectively. Non-relapse mortality on Day 100 was 23% and 42% at two years. Cumulative incidence of relapse/progression at two years was 31%. Kaplan-Meier estimated 1-year and 2-year overall survival with median follow up of 869 days (range 181-1932) is 41% and 28%, respectively.Conclusions This regimen allows successful haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning in high-risk patients lacking a suitable donor. (clinicaltrials.gov identifier:NCT00202917).