Effects of CD34+ cell dose on haematopoietic recovery in acute lymphoblastic leukaemia patients with positive pretransplant measurable residual disease.

Abstract

A higher CD34+ cell dose in allografts is associated with faster haematopoietic recovery after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Leukaemia stem cells impair normal bone marrow (BM) niches and induce BM failure during leukemogenesis. However, whether measurable residual disease (MRD), known as the persistence of low-level leukaemic cells, could influence the effects of CD34+ cell dose on haematopoietic recovery after transplantation in acute lymphoblastic leukaemia (ALL) patients is unknown. A total of 975 ALL patients were enrolled and classified into pre-HSCT MRD-positive and MRD-negative subgroups. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariate analysis was performed to determine independent influencing factors from the univariate analysis. An appropriate CD34+ cell dose was positively associated with faster haematopoietic recovery in the total ALL population. More importantly, in pre-HSCT MRD-positive ALL patients, a higher CD34+ cell dose (≥2.76 × 106 /kg) was related to faster neutrophil (HR 1.330, 95% CI 1.045-1.692, p=0.021) and platelet engraftment (HR 1.808, 95% CI 1.412-2.316, p < 0.001) in multivariate analysis. CD34+ cell dose was a crucial factor associated with either engraftment or transplant outcomes, although we did not demonstrate direct correlations of CD34+ cell dose with relapse, TRM, LFS or OS after allo-HSCT. Our results indicated that no additional CD34+ stem and progenitor cell harvests were needed to ensure successful haematopoietic recovery in pre-HSCT MRD-positive patients compared to pre-HSCT MRD-negative patients.