Abstract

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 × 10^6/kg and >8.25 × 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.

Highlights

  • Reduced intensity conditioning (RIC) regimens have been developed with aim to extend the use of allogeneic hematopoietic stem cell therapy to older patients and those with pre-existing comorbidities [1]

  • The probabilities of overall survival (OS) and Leukemia-free survival (LFS) at 2 years from transplantation for the whole study group were 64% and 60% (53-68), respectively

  • In the current study we have addressed the issue of the potential impact of peripheral blood (PB) grafts composition on the outcome of RIC allo-SCT

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Summary

Introduction

Reduced intensity conditioning (RIC) regimens have been developed with aim to extend the use of allogeneic hematopoietic stem cell therapy (allo-SCT) to older patients and those with pre-existing comorbidities [1]. The impact of PB stem cell grafts cellularity on the outcome of RIC allo-SCT is still controversial This is mainly due to the fact that inconsistent results have been reported regarding the influence of CD3+ and CD34+ cell doses on the incidence of graft-versus-host disease (GVHD), disease control and survival in the studies published so far [5,6,7,8,9,10,11,12,13]. In the current retrospective EBMT registry study we aimed to analyze the impact of CD3+ and CD34+ cell doses in PBSC grafts on the outcome of RIC allo-SCT in a homogeneous population of patients, taking into account aforementioned factors. We focused on the population of patients with AML allografted in first complete remission (CR1) from fully matched (10/10 match) unrelated donors (MUD) after year 2000

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