Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34 ⁺ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation

Abstract

© Ferrata Storti Foundation P.S. Martin et al. 500haematologica | 2016; 101(4) nificant impact on transplant outcomes in the RIC setting. However, relatively few studies have reported on productrelated outcome data in RIC transplants. These studies have primarily focused on CD34 + cell dose, most reporting that higher CD34 + cell doses are associated with more rapid engraftment with a variable effect on the incidence of graft-versus-host disease (GVHD) and survival outcomes. [1][2][3][4][5] Gomez-Almaguer and colleagues reported on 138 recipients of RIC hematopoietic stem cell transplants, showing that higher CD34 + doses correlated with improved overall survival. 6 A CIBMTR registry analysis of 1054 RIC hematopoietic stem cell transplant recipients found that lower CD34 + doses correlated with increased transplant-related mortality and decreased overall survival. 7 In contrast, Remberger and colleagues reported that higher CD34 + doses were actually associated with higher relapse rates and lower overall survival. 8 Relative to CD34 + cell dose, total nucleated cell (TNC) dose has been less frequently studied. However, in the limited number of studies that have examined TNC, a trend toward improved survival outcomes with higher TNC dose, independently of CD34 + dose, has been found. 9,10 The current study examines the impact of both TNC and CD34 + cell dose on major transplant outcomes in a cohort of 705 consecutive patients undergoing RIC allogeneic peripheral blood hematopoietic stem cell transplantation. MethodsWe analyzed data from 705 consecutive patients with hematologic malignancies undergoing RIC utilizing granulocyte colonystimulating factor-mobilized donor peripheral blood mononuclear cells as a graft source. Patients who underwent either in vivo T-cell depletion with antithymocyte globulin or ex-vivo T-cell depletion were excluded from the study. All patients had at least 3 years of follow-up after their transplant. All patients provided consent to the use of protected health data for research, as approved by a common institutional review board of the Dana-Farber/Harvard Cancer Center. Definitions and end-pointsNeutrophil engraftment was defined as the first day of an absolute neutrophil count >500/mL on three consecutive measurements. Platelet recovery was defined as the first day of two consecutive measurements of >20,000/mL (unsupported). Acute and chronic GVHD were graded by consensus grading criteria and their cumulative incidence was calculated through day +200 after hematopoietic stem cell transplantation. Chronic GVHD was defined clinically by treating physicians utilizing standard criteria ultimately supplanted by NIH Consensus Conference recommendations.11 Relapse was defined as disease recurrence documented by morphological, histological or radiographic means. Treatmentrelated mortality was defined as death while in continuous remission. Progression-free survival was defined as the time from transplantation to relapse or death from any cause, and overall survival was defined as ...

Graft Immune Cell Composition Associates with Clinical Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with AML

“…Our finding that a high CD34 + cell content in the graft predisposed to cGVHD may be related to CD34 + -derived dendritic cells that have been reported to be able to augment antigen presentation to donor T cells and induce cGVHD (46). It is of note that according to a recent study by Martin et al (47), estimates of the total number of nucleated cells, especially CD34 negative cells, might in fact be better predictors of HSCT outcome than the CD34 + cell dose at least in HSCT performed using RIC and PB.…”

CD3+ graft cell count influence on chronic GVHD in haploidentical allogeneic transplantation using post-transplant cyclophosphamide

“…Regarding the definition of a CD3+ threshold in relation to chronic GVHD incidence (only for the PBSC subgroup analysis), we compared quartiles referring to CD3+ graft content and reported the most significant result (1st + 2nd vs. 3rd + 4th quartile), which corresponds to the use of the median value of CD3+ graft content. Other studies used the quartiles to stratify graft cell content [20,21]. However, since CD3+ was considered as a continuous variable in the context of a multivariate model, a CD3+ threshold alone should not be considered as a precise risk factor.…”

Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide

“…38 Finally, our finding of improved GRFS and CRFS with higher total nucleated cell dose is consistent with the association of graft dose and improved overall survival in past studies. [39][40][41] By incorporating GvHD endpoints, GRFS and CRFS may prove useful in comparing allogeneic BMT platforms especially when reduction in GvHD is the desired clinical outcome. Moreover, GvHD composite endpoints may be better measures of successful allogeneic BMT, affording a more comprehensive picture of patients' outcomes than overall survival or disease-free survival alone.…”