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.

Autor: O’Donnell, P V, Jones, R J, Vogelsang, G B, Seber, A, Ambinder, R F, Flinn, I, Miller, C, Marcellus, D C, Griffin, C, Abrams, R, Braine, H G, Grever, M, Hess, A D, Piantadosi, S, Noga, S J
Předmět:
Zdroj: Bone Marrow Transplantation; 11/15/98, Vol. 22 Issue 10, p947, 9p
Abstrakt: 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 × 107 mononuclear cells/kg, 3.3 × 106 CD34+ cells/kg, 1.5 × 105 CFU-GM/kg and 5.5 × 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. Peri-transplant (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. [ABSTRACT FROM AUTHOR]
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