Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide

Shannon R McCurdy, Jennifer A Kanakry, Margaret M Showel, Hua-Ling Tsai, Javier Bolaños-Meade, Gary L Rosner, Christopher G Kanakry, Karlo Perica, Heather J Symons, Robert A Brodsky, Douglas E Gladstone, Carol Ann Huff, Keith W Pratz, Gabrielle T Prince, Amy E Dezern, Ivana Gojo, William H Matsui, Ivan Borrello, Michael A McDevitt, Lode J Swinnen, B Douglas Smith, Mark J Levis, Richard F Ambinder, Leo Luznik, Richard J Jones, Ephraim J Fuchs, Yvette L Kasamon, Shannon R McCurdy, Jennifer A Kanakry, Margaret M Showel, Hua-Ling Tsai, Javier Bolaños-Meade, Gary L Rosner, Christopher G Kanakry, Karlo Perica, Heather J Symons, Robert A Brodsky, Douglas E Gladstone, Carol Ann Huff, Keith W Pratz, Gabrielle T Prince, Amy E Dezern, Ivana Gojo, William H Matsui, Ivan Borrello, Michael A McDevitt, Lode J Swinnen, B Douglas Smith, Mark J Levis, Richard F Ambinder, Leo Luznik, Richard J Jones, Ephraim J Fuchs, Yvette L Kasamon

Abstract

Related HLA-haploidentical blood or marrow transplantation (BMT) with high-dose posttransplantation cyclophosphamide (PTCy) is being increasingly used because of its acceptable safety profile. To better define outcomes of nonmyeloablative (NMA) HLA-haploidentical BMT with PTCy, 372 consecutive adult hematologic malignancy patients who underwent this procedure were retrospectively studied. Risk-stratified outcomes were evaluated using the refined Disease Risk Index (DRI), developed to stratify disease risk across histologies and allogeneic BMT regimens. Patients received uniform conditioning, T-cell-replete allografting, then PTCy, mycophenolate mofetil, and tacrolimus. Six-month probabilities of nonrelapse mortality and severe acute graft-versus-host disease were 8% and 4%. With 4.1-year median follow-up, 3-year probabilities of relapse, progression-free survival (PFS), and overall survival (OS) were 46%, 40%, and 50%, respectively. By refined DRI group, low (n = 71), intermediate (n = 241), and high/very high (n = 60) risk groups had 3-year PFS estimates of 65%, 37%, and 22% (P < .0001), with corresponding 3-year OS estimates of 71%, 48%, and 35% (P = .0001). On multivariable analyses, the DRI was statistically significantly associated with relapse, PFS, and OS (each P < .001). This analysis demonstrates that the DRI effectively risk stratifies recipients of NMA HLA-haploidentical BMT with PTCy and also suggests that this transplantation platform yields similar survivals to those seen with HLA-matched BMT.

© 2015 by The American Society of Hematology.

Figures

Figure 1
Figure 1
Overall outcomes of NMA haplo BMT with high-dose posttransplantation cyclophosphamide. (A) Progression-free and overall survival. (B-D) Cumulative incidences by competing-risk analysis of relapse and nonrelapse mortality (B), acute graft-versus-host disease (C), and any chronic graft-versus-host disease (D). Point estimates are provided in Table 2.
Figure 2
Figure 2
Risk-stratified outcomes of NMA haplo BMT based on refined DRI group. (A) Progression-free survival. (B) Overall survival. (C) Cumulative incidence of relapse. (D) Cumulative incidence of nonrelapse mortality. Point estimates are provided in Table 2. Int., intermediate; V, very.
Figure 3
Figure 3
Disease-specific relapse risks. Cumulative incidences by competing-risk analysis of relapse in intermediate-risk aggressive NHL (n = 84) (A) and relapse in intermediate-risk AML (n = 64) (B) based on refined DRI grouping.

Source: PubMed

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