Impact of Myeloablative and Reduced Intensity Conditioning On Outcomes After Unrelated Cord Blood Transplantation for Adults with Acute Lymphoblastic Leukemia.
Authors: Tucunduva Luciana , Ruggeri Annalisa , Sanz Guillermo , Furst Sabine , Rio Bernard , Socie Gerard , Arcese William , Michallet Mauricette , Yakoub-Agha Ibrahim , Cornelissen Jan J , Sanz Miguel Angel , Montesinos Pau , Purtill Duncan , Gluckman Eliane , Rocha Vanderson 
Published: October 2019

Abstract
Abstract 3117
Allogeneic hematopoietic stem cell transplantation is the only curative option for high risk or relapsed acute lymphoblastic leukemia (ALL) in adults. In the absence of an HLA identical sibling donor, HLA matched adult donor or HLA mismatched cord blood are alternative sources of stem cell to treat those patients. However, very few data on the outcomes after umbilical cord blood transplantation (UCBT) for adult ALL using myeloablative or reduced intensity conditioning regimens have been reported. With this aim, we conducted a retrospective survey on the outcomes after UCBT for adult ALL and a more specific analysis for patients with cytogenetic data transplanted in remission with either a myeloablative (MAC) or reduced intensity conditioning regimen (RIC). From 1996 to 2011, 433 adult patients (pts) received a UCBT for ALL. Overall 2-year LFS was 37% for pts in first complete remission (CR1) (n=199), 32% for CR2 (n=138) and 9% for advanced disease (n=96). Complete cytogenetic information at diagnosis was available for 316 pts, of those 251 pts were transplanted in CR1 (63%, n=157) or in CR2 (37%, n=132). Median age at UCBT was 33 years (18 to 66 years) and 76% of the pts (n=191) had an abnormal karyotype at diagnosis. Pts were analyzed according to the presence of t(9;22) as Ph+ (n=115) and Ph- (n=136). Double CBT was performed in 109 pts (43%) and the median total nucleated cell dose at freezing was 4.02×107/kg. Most pts received CBU with one (30%, n=74) or two (56%, n=136) HLA disparities. A myeloablative (MAC) conditioning was given to 177 pts (70%) and 73 (30%) received a reduced intensity conditioning (RIC). Overall 2-year leukemia- free survival (LFS) was 36±3%; 37% for Ph- and 35% for Ph+ pts (p=0.74). On multivariate analysis, 3 factors were associated with improved LFS: age <44 years (HR: 0.6, p=0.004), CR1 at transplant (HR: 0.6, p=0.005) and use of RIC (HR: 0.6, p=0.015). Since the outcomes were different according to disease status and conditioning intensity, a subgroup analysis was performed. Results are shown in Table 1.
In pts transplanted with MAC (n=177), most frequent conditioning regimens were Cy-TBI (27%) and Bu+Flu+Thio (25%). Median follow-up (FU) was 26 and 35 months for those in CR1 (n=107) and CR2 (n=70), respectively. Cumulative incidence (CI) of 60-day neutrophil recovery was 87% for pts in CR1 and 83% for those in CR2; acute GVHD was 43% and 37%, respectively. Two-year CI of NRM was 41% for CR1 and 49% for CR2 and 2-year RI was 24% for CR1 and 22% for CR2. Two-year LFS was 35% for CR1 and 30% for CR2. No factor was found to be associated with LFS, relapse nor NRM. One-hundred and four pts died, 81 of transplant-related causes (79%, n=46 for CR1 and 74% n=35, for CR2), mainly due to infections (53% n=24 for CR1 and 38% n=12 for CR2).
In pts transplanted with RIC (n=94), Cy+Flu+TBI regimen was used in 74% (n=54). Median FU was 31 and 34 months and median age was 50 and 39 years for those in CR1 (n=49) and CR2 (n=24), respectively. At 2 years, CI of NRM was 22% for CR1 and 17% for CR2. Two-year RI was 30% and 47%, respectively. Two-year LFS was 49% for CR1 and 36% for CR2. For pts in CR1, univariate analysis showed that younger age (< 50 years) was associated with improved LFS (62% × 36%, p=0.042) and lower NRM. Eighteen patients died, 6 of relapse and 12 of transplant-related causes. All patients who died from NRM were 50 years or older.
UCBT is an option to treat high risk and relapsed adult ALL. Pts transplanted with MAC had an LFS comparable with that reported with other stem cell sources, but strategies to reduce toxicity are still needed, especially for pts in CR2. Results with RIC are encouraging and may be considered in younger pts. Importantly, in this large series outcomes after UCBT for Ph+ ALL were not statistically different from those compared to Ph-.
Table 1. Outcomes according to disease status at UCBT and conditioning regimen MAC RIC CR1 (n=107) CR2 (n=70) CR1 (n=49) CR2 (n=24) LFS (2y) 35 ± 5% 30 ± 6% 49 ± 7% 36 ± 10% Relapse (2y) 24 ± 4% 22 ± 5% 30 ± 7% 47 ± 11% NRM (2y) 41 ± 5% 49 ± 6% 22 ± 6% 17 ± 8%

Disclosures:
No relevant conflicts of interest to declare.