CD34+ stem cell augmentation of elutriated allogeneic bone marrow grafts: Results of a phase II clinical trial of engraftment and graft-versus-host disease prophylaxis in high-risk hematologic malignancies

P. V. O'Donnell, R. J. Jones, G. B. Vogelsang, A. Seber, R. F. Ambinder, I. Flinn, C. Miller, D. C. Marcellus, C. Griffin, R. Abrams, H. G. Braine, M. Grever, A. D. Hess, S. Piantadosi, S. J. Noga

Research output: Contribution to journalArticlepeer-review

Abstract

Although T cell depletion of allografts used in BMT has reduced GVHD, it has been associated with inferior engraftment and an increased risk of relapse. We have found that T cell depletion by counterflow centrifugal elutriation (CCE) also results in depletion of CD34+ stem cells. In order to determine if the discarded CD34+ cells would improve engraftment, we undertook a phase II trial of allogeneic BMT in which 110 patients (median age 43) with a variety of hematologic malignancies received CD34+ stem cell augmented, elutriated marrow grafts. The T cell-depleted grafts were tightly controlled and contained a mean of 4.3 x 107 mononuclear cells/kg, 3.3 x 106 CD34+ cells/kg, 1.5 x 105 CFU-GM/kg and 5.5 x 105 CD3+ T cells/kg. Median time to engraftment of granulocytes (> 500/μl) was 16 days and of platelets (> 50,000/μl) was 25 days, comparable to that seen with unmanipulated marrow. No mixed hematopoietic chimerism was observed that was not associated with disease relapse. The four patients (3.6%) who failed to engraft were all at high risk because of prior donor transfusions or underlying marrow disorders. The incidence of GVHD was dependent on the duration of cyclosporin A (CsA) immunosuppression. In patients who received CsA for ≥ 80 days, the incidence of clinically significant acute GVHD (> stage 1) and extensive, chronic GVHD was 5% and 11%, respectively. Peritransplant (≤ 100 day post-BMT) mortality for this group of patients was 15%. Event-free survival in selected subsets of patients compared favorably to previous studies in which patients received unmanipulated marrow allografts.

Original languageEnglish (US)
Pages (from-to)947-955
Number of pages9
JournalBone marrow transplantation
Volume22
Issue number10
DOIs
StatePublished - 1998

Keywords

  • Allogeneic BMT
  • CD34
  • Elutriation
  • GVHD
  • Hematologic malignancies
  • Mortality

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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