Unrelated Cord Blood Transplantation (UCBT) in Adult and Pediatric Acute Lymphoblastic Leukemia: Impact of Minimal Residual Disease on Relapse and Survival,
Authors: Bachanova Veronika , Burke Michael J , Brunstein Claudio , Verneris Michael R , Cao Qing , Wagner John E. , Weisdorf Daniel J. 
Published: October 2019

Abstract
Abstract 4114

Background:
Umbilical cord blood (UCB) has become a valuable alternative source of stem cells for patients with high risk acute lymphoblastic leukemia (ALL) lacking a matched sibling donor. Data on the efficacy of transplant outcomes after UCB in ALL are limited, particularly for the adult population.

Methods:
We report the outcomes of 143 patients (74 children <18 years and 68 adults) with ALL who received UCBT at University of Minnesota between 1999–2010. Most had precursor-B ALL (n=87 [61%]), Philadelphia positive ALL (Ph+; n=41 [29%] and T cell ALL (n=15 [10%]). All except 7 patients were in complete remission (CR1: n=59 [41%] or CR2/CR3: n=77 [54%]). Most adults received double UCB grafts (adult =90% vs. children =27%, p=0.01) with HLA locus matching of 4/6 and 5/6 in 65% and 28% of adults vs. 29% and 53% of children (p=0.01). 86 had an assessment of Minimal Residual Disease (MRD) prior to UCBT using 4 to 6 color flow-cytometric analysis and MRD was based on prior (diagnostic) immunophenotype and according to published standards. Ten patients had MRD detected immediately prior to UCBT (2 patients were in CR1, 7 in CR2, 1 in CR3) and 76 patients were MRD-negative.
Most patients (82%) received myeloablative conditioning (cyclophosphamide 120 mg/kg, fludarabine 75mg/m2 and total body irradiation (TBI) 1200–1320cGy). Non-myeloablative conditioning (cyclophosphamide 50mg/kg, fludarabine 200mg/m2 and TBI 200cGy was given to patients above 45 years (n=18 [13%]) and in those with poor fitness (n=8 [5%]). All patients received cyclosporine (day −3 to day +180) and mycophenolate mofetil ( day −3 to day +45) post-HCT.

Results:
The cumulative incidence of neutrophil engraftment by day 42 was 97% (95%CI 92–99%). Six months platelet engraftment was 71% (95%CI 67–85%), 48% (95% CI 32–64%) and 84% (95%CI 58–100%); p<0.01) for patients ≤18 years, 19–45 and >45 years of age, respectively. With a median follow-up of 3.9 years (0.5–11.8 years), the 3-year leukemia-free survival (LFS) and overall survival (OS) was 47% (95%CI 38–55%) and 49% (95%CI 40–57%) with trend to better OS in children (Table). Cumulative incidence of relapse at 1 year was 17% (95%CI 11–23%) and the relative risk tended to lower rates in adults following MA vs NMA conditioning (7% [95%CI 0–14% vs 21% [95%CI 5–37%]; p=0.19). In univariate analysis age, disease status (CR1 vs CR2/CR3 vs. non CR), disease group (pre-B ALL, Ph+ALL, T-ALL) or time to transplant had no impact on relapse rate. Treatment-related mortality at 1 year was higher in adult patients aged 18–45 years (46% [95%CI 31–61%]) compared to children (19% [95%CI 10–28%]) or older patients who received NMA conditioning regimen (TRM 5% [95%CI 0–15%]; p<0.01). Patients with MRD detected immediately prior to UCBT had a higher relative risk of relapse at 2 years (30% [95%CI 4–56%]) and lower LFS (30% [95%CI 7–58%]) compared to MRD- group (16% [95%CI 8–25%]; p=0.05 and 61% [95%CI 49–70%]; p=0.05); respectively.

Conclusion:
UCBT expands the options for patients with ALL and offers potent protection from post-transplant relapse. Our results indicate that novel strategies in UCB HCT for ALL should focus on decreasing TRM in adult patients receiving myeloablative conditioning and improving leukemia control to induce a MRD- state pre- transplant.

Disclosures:
No relevant conflicts of interest to declare.