Donor-to-Recipient Weight Ratio Is Independently Associated with CD34+ Yield in Healthy Donors Undergoing Peripheral Blood Stem Cell Collection for Allogeneic Transplantation
Authors: Fiala Mark A , Park Soo , Abboud Camille N. , Cashen Amanda F. , Jacoby Meagan , Pusic Iskra , Romee Rizwan , Schroeder Mark A. , Uy Geoffrey L. , Vij Ravi , Westervelt Peter , Wildes Tanya M , DiPersio John F. , Stockerl-Goldstein Keith E. 
Published: October 2019

Abstract
Background: Over the past two decades, peripheral blood stem cells (PBSC) have surpassed bone marrow as the preferred graft source for adult allogeneic transplantation due to its more rapid engraftment and potentially better graft-vs-tumor effects, and because PBSC collection is much less invasive for the donor. The optimal CD34+ PBSC dose is ≥ 4.0x106cells/kg, but doses ≥ 8.0x106cells/kg are suggested by some for reduced-intensity conditioning and haploidentical transplants. There is no established minimum CD34+ PBSC dose, but doses below 2.0x106cells/kg have been associated with a higher risk of engraftment delay and failure. There is significant inter-donor variability in the ability to mobilize PBSCs. Several factors have been identified as predictors of PBSC mobilization in healthy donors including: gender, age, weight, body mass index (BMI), and blood counts before and after mobilization. The impact of the donor’s comorbidities on mobilization is currently unknown.
Patients/Methods: We performed retrospective chart review of 488 consecutive adult patients who underwent apheresis for allogeneic stem cell donation at Washington University School of Medicine from 2006 through 2013. Patients who received any collection regimen other than 10mcg/kg of G-CSF daily with 20 liters (+/-10%) apheresis on Day 5 were excluded. Patients who had undergone a previous apheresis for stem cell donation were excluded. Univariate analysis was performed to identify predictors of CD34+ PBSC collection in a single apheresis. Variables analyzed were: gender; age; weight; BMI; donor-to-recipient weight ratio; pre and post-mobilization blood counts (white blood count [WBC], hematocrit, platelets, neutrophils, lymphocytes, and monocytes); pre-mobilization glucose and triglyceride levels; post-mobilization peripheral blood (PB) CD34+count; and medical history significant for hypertension, hyperlipidemia, or diabetes mellitus. Subsequently, a linear regression multivariate analysis was performed with all variables found to be significant in the univariate analysis. 2-tailed tests for significance were used throughout the analysis.
Results: 304 patients met the eligibility criteria for analysis. The median age was 53 years (range 18-76), 90% were Caucasian, and 50% were male. The median number of CD34+ cells collected was 7.4 x106/kg (range 0.8-27.1). 97% (295) collected ≥ 2.0x106 CD34+cells/kg, 81% (247) collected ≥ 4.0x106 CD34+cells/kg, and 44% (134) collected ≥ 8.0x106 CD34+ cells/kg. Post-mobilization PB CD34+ count (r= 0.841, p <0.001) and donor-to-recipient weight ratio (r= 0.439, p <0.001) were the strongest correlates with CD34+ collection. Weak correlations were seen with post-mobilization neutrophils (r= 0.360, p <0.001), WBC (r= 0.353, p <0.001), and hematocrit (r= 0.207, p <0.001); weight (r=0.280, p <0.001); BMI (r= 0.229, p <0.001); and age (r= -0.207, p <0.001). Male donors collected 9.1x106 CD34+ cells/kg compared to 7.5 x106 CD34+ cells/kg for females, on average (p = 0.003). Hypertension, hyperlipidemia, and diabetes mellitus were not associated with Day 1 CD34+ collection. We performed a multivariate model with the variables: post-mobilization PB CD34+ count; donor-to-recipient weight ratio; gender; post mobilization neutrophil, WBC, and hematocrit; weight; BMI; and age. In this analysis, post-mobilization PB CD34+count, donor-to-recipient weight ratio, and age were all independently significant.
Conclusion: After one apheresis, the majority (81%) of donors collected ≥ 4.0x106 CD34+ cells/kg, the optimal number of CD34+ cells for standard allogeneic transplant, but only 44% were able to collect ≥ 8.0x106, the suggested number of CD34+ cells for reduced-intensity or haploidentical transplants. As these reduced-intensity and haploidentical transplants increase in frequency, the need for more accurate predictors of CD34+cell collection will also increase. Donor-to-weight ratio could be a useful tool to stratify potential donors for reduced-intensity and haploidentical transplants. In this study, 63% of donors with a donor-to-recipient weight ratio > 1.0 collected ≥ 8.0x106 CD34+cells/kg, while only 20% of donors with a donor-to-recipient weight ratio ≤ 1.0 did. While gender, weight, and BMI have previously been reported as predictors for CD34+ collection, they potentially were just surrogates for donor-to-recipient weight ratio.

Disclosures
No relevant conflicts of interest to declare.