Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies

Abstract

We present a comparative study on 124 patients with hematologic malignancies who had undergone reduced-intensity conditioning and then received a transplant from an HLA-matched related (MRD), an HLA-matched unrelated (MUD), or an HLA-haploidentical related (HAPLO) donor. The conditioning regimen, which consisted of fludarabine, melphalan or busulfan, and alemtuzumab was administered to patients with lymphoid (n = 62) or myeloid disease (n = 62). Mycophenolate mofetil was used as prophylaxis for graft-versus-host disease (GVHD), and 38, 58, and 33 patients received transplants from MRD, MUD, and HAPLO donors, respectively. Only 2 patients experienced primary graft failure (GF) after melphalan-based regimen, whereas 8 of the 17 patients who received a transplant from HAPLO donors experienced a primary GF after busulfan-based regimen. The cumulative incidence of grade III to IV acute GVHD in engrafted patients who had received transplants from MRD, MUD, or HAPLO donors was 3%, 11%, and 27%, respectively, and the 2-year overall survival (OS) rates were 51%, 22%, and 23%, respectively. According to multivariate analysis, transplantation from either MUD or HAPLO donors compared with MRD were adverse factors that affected the OS (P = .006 and P = .002, respectively). In conclusion, the reduced-intensity regimen that included fludarabine, busulfan, or melphalan and alemtuzumab using only mycophenolate mofetil as the GVHD prophylaxis conferred favorable outcomes in the MRD group but lower survival rates in the MUD and HAPLO groups. The busulfan-based regimen led to a high incidence of GF in the HAPLO group, suggesting the need for modification or intensification of immunosuppression.

Keywords: Alemtuzumab; Haploidentical; Matched-related; Matched-unrelated; Reduced-intensity.

Conflict of interest statement

Conflict of interest statement: There are no conflicts of interest to report.

Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Cumulative incidence of acute and chronic GVHD. Black line shows HLA-matched related donor (MRD), dotted line shows HLA-matched unrelated donor, and gray line shows HLA-haploidentical related donor (HAPLO).

Figure 2

Probability of disease-free survival, progression-free survival, and overall survival. Black line shows HLA-matched related donor (MRD), dotted line shows HLA-matched unrelated donor, and gray line shows HLA-haploidentical related donor (HAPLO).

Figure 3

Cumulative incidence of relapse and nonrelapse mortality. Black line shows HLA-matched related donor (MRD), dotted line shows HLA-matched unrelated donor, and gray line shows HLA-haploidentical related donor (HAPLO).

Figure 4

Immune recovery of the (A) CD3+, (B) CD4+, and (C) CD8+ T cells. The median values before transplantation and 1.5, 3, 6, and 12 months after transplantation are shown with the standard error bars. Black line shows HLA-matched related donor (MRD), dotted line shows HLA-matched unrelated donor, and gray line shows HLA-haploidentical related donor (HAPLO).