Decreased Incidence of Relapse in Patients with Acute Leukemia Transplanted from Matched Unrelated Donors: Induction of GvL.
Authors: Arellano Martha L. , Langston Amelia , Lonial Sagar , Flowers Christopher , Khoury Jean H. , Winton Elliott , Waller Edmund K. , Mary Lechowicz J. 
Published: October 2019

Introduction: Previous studies have suggested a greater graft versus leukemia (GvL) effect among patients (pts.) with chronic myeloid leukemia (CML) who received hamatopoietic progenitor cell transplants (HPCT) from volunteer unrelated donors (VUD) compared with CML pts. who received matched related donor (MRD) transplants. We analyzed the incidence of relapse and survival among pts. with acute leukemia (AL) to determine whether graft source (VUD vs. MRD) had an impact on relapse or survival after allogeneic HPCT.

Methods: We analyzed 308 pts. with AML (N=228) and ALL (N=80) who received BM or blood HPCT from MRD (N= 224) or VUD (N= 84). The primary goal was to determine the incidence of post-transplant relapse and factors associated with relapsed disease. The secondary endpoint was survival. Relapsed disease was defined as presence of active leukemia (by morphologic, flow cytometric, cytogenetic, or molecular testing) at the time of transplant. Kaplan-Meier estimates of relapse and survival were calculated, and log rank statistics were used to compare the survival curves. 2-tailed t-tests were used to compare characteristics among relapsed pts. Significant variables on univariate analysis were entered into a Cox regression model for multivariable analysis. A p-value ≤ 0.05 was deemed significant. IRB approval was obtained for this retrospective study.

Results: 72/228 (32%) pts. with AML and 27/80 (34%) pts. with ALL relapsed at a median of 135 days post-transplant. Relapse was significantly higher among pts. with active leukemia at the time of transplant (44/99, 44%) and in recipients of grafts from MRD (82/224, 37%), compared with patients in remission (55/209, 26%) at time of transplant and recipients of VUD grafts (17/84, 20%) (p= 0.008 and 0.003 respectively). Stratifying for disease status at transplant, the graft source was significantly associated with the incidence of relapse only in the subset of 99 pts. with active disease at transplant, with 78% relapse among pts. with active AL who received MRD transplants compared with 42% relapse among pts. with active AL transplanted with grafts from VUD (P=0.03) (fig. 1). However, there was no significant difference in overall post-transplant survival among recipients of MRD and VUD (P=0.82).

Fig. 1. Fig. 1.

Relapsed and non-relapsed pts. had similar age, graft type (PBSC vs. BMT), conditioning regimen, and GVHD prophylaxis (data not shown).

Conclusions: Overall outcome for pts. with AL who receive allogeneic transplants with active disease at the time of transplant is poor. While pts. with active AL transplanted with grafts from VUD have less post-transplant relapse than those transplanted with grafts from MRD, overall survival was similar due to greater non-relapse mortality. While this retrospective study could not account for other significant factors that may affect relapse, such as the longer interval from diagnosis to transplant for recipients of VUD grafts, these results indicate that decreasing treatment-related mortality may accentuate the benefit of the enhanced GvL effect of VUD transplant.