An International Multi-Institutional Study of Double Cord Blood Transplantation in a Racially Diverse Population.
Authors: Ballen Karen , Wang Brian , Rosenthal Joseph , Nademanee Auayporn , Karanes Chatchada , Jaing Tang-Her , Graham Michael , Tan Patrick , Gjertson David , Petz Lawrence , Forman Stephen , Chow Robert 
Published: April 2020

Abstract
Cord blood (CB) is an alternative stem cell source for patients, but single CB products may not contain sufficient cell dose for cord blood transplantation (CBT) of adults. Double cord blood transplantation (DCBT) has been used to increase the cell dose, but the majority of reported patients have been Caucasian. We conducted a retrospective analysis of 89 consecutive DCBT recipients who received at least one CB product from the StemCyte CB banks. The median age was 20 years (range 1–63), with 58% over age 18, and the median weight was 60 kg (range 11–137), with 70% ≥ 50 kg. Diagnoses were: 29 ALL, 23 AML, 10 Thalassemia, 6 CML, 5 MDS, 4 AA, 3 lymphoma, and 9 others. 33% had IBMTR advanced disease status, 28% intermediate, 18% early, and 21% unknown status for the leukemia/lymphoma/MDS cases. 70% of the recipients with known race were non-Caucasian (NC) with 35 Asians (A), 24 Caucasians (C), 9 African Americans, 8 Hispanics, 3 Native Americans, 10 others. Patients were treated with a variety of conditioning regimens (33% reduced intensity) at 39 U.S. and international centers on 4 continents with 37% at non-US centers. Thirty-seven patients (42%) received both units as plasma depleted cord blood products. CB product characteristics were as follows: median pre-freeze TNC dose 3.8×107/kg, median pre-freeze CD34+ dose 1.4×105/kg. The median time to neutrophil (ANC500) engraftment was 21.5 days and the median time to platelet (Plt) 20K and 50K engraftment were 42 and 59 days respectively. Kaplan-Meier (KM) estimates of 100-day transplant related mortality (TRM), 1-year overall (OS) and disease free survival (DFS) were 37±6%, 50±6%, and 37±6% respectively. Causes of death include infection (26%), relapse (23%), multi-organ failure (16%), GvHD (2%), and other (33%). Engraftment correlated with cell dose and disease risk status in univariate analysis. Survival correlated with higher pre-freeze TNC dose (p=.03), higher pre-freeze CD34+ dose (p=.04), and non-washed CB (p=.01). Survival, disease-free survival, ANC 500, plt 20K, and 50K engraftment, and TRM were not different between C and NC or between A and Non-Asians (NA) in multivariate analyses. 1-year OS for C and NC patients were 48% and 54% respectively (p=.24), with DFS of 35% and 40% (p=.32), respectively. In conclusion, this multi-centered international study shows that 1) DCBT can be performed effectively on a racially diverse patient population, 2) Survival and other outcome measures were similar between C and NC or between A and NA patients in multivariate analyses, 3) Cell dose remains important for engraftment even with DCBT.
ANC500 Plt 20K 1 Yr Relapse 100-Day & 1-Yr TRM 1-Yr OS 1-Yr DFS * W = Washed CB, NW = Unwashed, CI = Cumulative Incidence; P-values from multivariate Cox Regression model adjusting for recipient weight, malignancy, and # of StemCyte units involved in DCBT. % & Median Days to Engraftment CI 83±7 KM 90±4 21.5 days CI 57±7 KM 78±7 42days 31±7 21±4 37±6 50±6 37±6 P-values* C vs. NC (W) .34 .86 .86 .87 .92 .86 C vs. NC (NW) .06 .59 .90 .35 .72 .92 A vs. NA (W) .43 .15 .80 .33 .13 .66 A vs. NA (NW) .69 .37 .75 .70 .30 .30