Unrelated Transplants for Poor Prognosis Adult Acute Lymphoblastic Leukemia: Long-Term Comparative Analysis Based on the Hematopoietic Progenitor Source.
Authors: Ferra Christelle , Sanz Jaime , Camara Rafael , Sanz Guillermo , Bermudez Arancha , Valcarcel David , Rovira Montserrat , Serrano David , Caballero Dolores , Espigado Ildefonso , Morgades Mireia , Heras Inmaculada , Solano Carlos , Barrenetxea Cristina , Duarte Rafael , Garcia-Noblejas Ana , Diez José Luis , Iriondo Arturo , Carreras Enric , Sierra Jordi , Sanz Miguel A. , Ribera Josep M. 
Published: October 2019

Abstract
Background: Adults with high risk ALL features at diagnosis, slow responders or with recurrent disease have a poor outcome with standard chemotherapy and are considered for unrelated transplants in most centers if a matched sibling donor is not available. Unrelated cord blood (UCB) has emerged as an option for unrelated transplant in adult patients.
Aim of the study: to compare the outcome of adult patients with unrelated transplant for poor prognosis ALL based on the hematopoietic source used for transplant.
Patients and Methods: One hundred and forty- nine adult patients (median 29 years [15–59], 90M/59F) with poor prognosis ALL received an unrelated transplant in 13 Spanish institutions from 2000 to 2007. Patients in 1st CR at transplant met at least one adverse prognostic factor (adverse cytogenetics, hyperleukocytosis or a slow-responder). ALL was of precursor B lineage in 111 (74%), T-cell lineage in 28 (19%) and undetermined lineage in 10 (7%) patients. ALL was in 1st CR in 81 (54%) patients, in 2nd CR in 37 (25%), in 3rd CR in 11 (7%) and overt disease in 20 (13 %) patients. Both groups were comparable for the main clinical and biologic ALL features except for patients with more overt disease in UCB transplant group. Conditioning therapy consisted on TBI-CY in 68 (46%), BU-CY in 9 (6%), Thiotepa- BU-CY/FLU in 60 (40%) patients (all of them UCB transplants) and other regimens in 12 (8%) patients (6 of them were non-myeloablative). The source of hematopoietic progenitors was UCB in 62 (41%), mobilized PB in 41 (28%) and BM in 46 (31%) patients. HLA compatibility requirements for selecting unrelated donors (BM and mobilized PB) were 7–8 out of 8 allelic identities, and for UCB were 4–6 out of 6 A / B antigenic and DR allelic identities.
Results: Acute GVHD was most frequent after PBSCT and BMT thanin UCBT. There was no significant difference for limited and extensive chronic GVHD between UCBT and PBSCT/BMT. The median follow-up was 16 months (0.3–101.4). DFS estimated at 5 years for patients transplanted with any source was not significantly better in transplants in 1st CR versus 2nd CR or more advanced disease (median 12 [2–22] vs 5 [2–9], p=0.106). There was no statistical difference in OS or DFS at 5 years between UCB and PBSCT/BMT). TRM was significantly lower in UCB transplants (p=0.021). The relapse probability was 17% for the PBSCT/BMT versus 29% for UCBT (p=0.088). The use of TBI as conditioning therapy was not associated with a lower relapse rate.
5y-OS (95%CI) Median OS (month, 95%CI) 5y-DFS (95%CI) Median DFS (month, 95%CI) 5y-TRM (95%CI) *p=0.021 Whole series 26% (17–35) 10 (4–17) 21% (13–29) 7 (3–11) 54% (44–64) PBSCT/BMT 22% (11–33) 9 (2–17) 21% (11–31) 5 (2–9) 63% (50–76)* UCBT 33% (18–48) 15 (7–22) 22% (8–36) 9 (1–17) 39% (25–53)* 1st CR ALL 30% (16–44) 12 (0–29) 24% (11–37) 12 (2–22) 57% (43–71) PBSCT/BMT 27% (9–45) 27 (2–51) 24% (8–40) 12 (2–22) 63% (44–82) UCBT 35% (14–56) 10 (0–23) 24% (4–44) 10 (0–26) 50% (31–69)
GVHD was the main cause of death for unrelated PBSCT/BMT in contrast with infection and relapse for UCBT (p=0.001).
Conclusions: UCB transplant and unrelated PBSCT/ BMT are equivalent options for poor prognosis adult ALL patients without a sibling donor. However, all modalities are associated with high transplant related mortality.