Effect of Graft Source on Unrelated Donor Hemopoietic Stem Cell Transplantation in Adults with Acute Myeloid Leukemia after Reduced-Intensity or Nonmyeloablative Conditioning: A Study from the Société Francaise de Greffe de Moelle et de Thérapie Cellulaire

Abstract

This retrospective report compared the 4-year outcomes of allogeneic stem cell transplantation (allo-SCT) in 651 adult patients with acute myeloid leukemia receiving a reduced-intensity (RIC) or nonmyeloablative conditioning (NMA) regimen according to the type of unrelated donors. These were either umbilical cord blood (UCB, n = 205), a 9/10 mismatched unrelated donor (MisMUD, n = 99), or a 10/10 matched unrelated donor (MUD, n = 347) graft. Neutrophil recovery was slower in UCB (74.5% by day 42) compared with MisMUD (94.8%) and MUD (95.6%) (P < .001). There was no significant difference in nonrelapse mortality between UCB and both MUD (hazard ratio [HR], 1.05; 95% confidence interval [CI], .62 to 1.78; P = .85) and MisMUD (HR, 1.58; 95% CI, .88 to 2.83; P = .13) The relapse/progression was similar between UCB and MisMUD (HR, .62; 95% CI, .37 to 1.03; P = .07), but was significantly lower in MUD compared with UCB (HR, .60; 95% CI, .39 to .92; P = .02). The rate of extensive chronic graft-versus-host disease (GVHD) was similar between UCB and both MUD (HR, 2.15; 95% CI, .93 to 4.97; P = .08) and MisMUD (HR, 1.84; 95% CI, .68 to 4.95; P = .23). The rate of severe grade III and IV acute GVHD was significantly increased in MisMUD compared with UCB (HR, 2.61; 95% CI, 1.30 to 5.23; P = .007). There was no significant difference in overall survival between UCB and both MisMUD (HR, .98; 95% CI, .66 to 1.45; P = .92) and MUD (HR, .74; 95% CI, .52 to 1.03; P = .08). These data suggest that in the setting of RIC/NMA, allo-SCT UCB is a valid alternative graft source, with significantly less chronic GVHD, compared with MisMUD, when there is no MUD available or when urgent transplantation is needed.

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

“…In addition, several recent studies demonstrated highly similar survival results between CBT and MSD recipients [12][13][14]27,45,46]. However, in this study, the rate of OS after CBT was significantly inferior to that after BMT or PBSCT from MSDs.…”

Wanted: Prospective Studies of Alternative Donors

“…In a world where most retrospective studies show similar outcomes between MUD, misMUD, and CB, as in the Malard et al study [5], and now add haplo-identical donors, how do these data help us move the alternative donor transplantation field forward? Although there is no single answer Biology of Blood and Marrow Transplantation j o u r n a l h o m e p a g e : w w w .…”

“…In this issue of Biology of Blood and Marrow Transplantation, Malard et al reported on the outcomes of CB compared with MUD and misMUD after reduced-intensity or nonmyeloablative conditioning [5]. Although we could be tempted to dissect differences in patient populations to explain their effect, or lack thereof, on the results, the message would not change.…”

“…Not addressed in the study by Malard et al [5] is the fact that there is a "new kid on the block," the unmodified partially HLA-matched related donor (haplo-identical) bone marrow with post-transplantation cyclophosphamide (pTCy) as GVHD prophylaxis [7]. This new strategy for an old donor type has been rapidly growing, especially in regions where access to the unrelated donor or CB pool is limited.…”

“…The study of Malard et al included patients treated between 2002 and 2010, reflecting the era of rapid growth in use of CB [5]. Along with the growth in utilization, several groups and institutions started studies that have improved the safety and efficacy of CB transplantation, in particular by targeting the slower and lower engraftment rates compared with matched sibling donor and MUD as shown in the Malard et al data [5]. These studies to improve homing or ex vivo expansion of progenitor cells are ongoing.…”