Unrelated Cord Blood Transplantation in Patients with Hematologic Malignancies in Brazil – A Sociedade Brasileira De Transplantes De Medula Ossea and Eurocord Collaborative Study.
Authors: Rodrigues Celso Arrais , Setubal Daniela , Bonfim Carmem , Nabhan Samir Kanaan , Colturato Vergílio Antônio Renzi , Mauad Marcos Augusto , de Souza Mair Pedro , de Azevedo Alexandre Mello , Hamerschlak Nelson , Seber Adriana , Bittencourt Henrique , Gonçalves Matheus Vescovi , de Castro Claudio Galvao , Dulley Frederico L. , De Souza Carmino Antonio , Chaves Wagnara , Neto Jose Zanis , Pasquini Ricardo , Gluckman Eliane , Rocha Vanderson , Bouzas Luis Fernando 
Published: October 2019

Abstract
Abstract 1211
Poster Board I-233
Umbilical cord blood transplantation (UCBT) has extended the availability of allogeneic hematopoietic stem cell transplantation to patients without HLA identical donors, mainly for groups of patients with high frequency of rare haplotypes such as the Brazilian population. We evaluated 173 patients who received a single first UCBT in Brazil between with 1993 and 2009 for hematological malignancies from 13 transplant centers. Median age was 8 years (range 1-60) and 58% were male. Sixty-nine patients (40%) had acute lymphoblastic leukemia, 57 (33%) acute myelogenous leukemia, 23 (13%) myelodysplastic syndrome, 18 (10%) chronic myelogenous leukemia and 6 (4%) chronic lymphoid diseases (4 Hodgkin's lymphoma, 1 non-Hodgkin lymphoma and 1 chronic lymphocytic leukemia). Most patients (55%) were transplanted in advanced phases of their diseases. Based on antigen-level HLA-A and -B and allele-level HLA-DRB1 typing, 64 patients (52%) received a cord blood unit with 2 mismatches, 54 (44%) with one mismatch and 5 (4%) received matched units. Conditioning regimen varied according to the disease and the center. Cord blood (CB) units came from CB banks from the USA (n=86), Europe (n=64), and Brazil (n=23). Most patients (94%) received a myeloablative regimen; TBI was used in 86% of cases and ATG/ALG in 82%. Median number of total nucleated cells infused was 4.4×107/kg of recipient weight and the median number of CD34+ cells infused was 1.7×105/kg. Median follow-up time of survivors was 30 months. The cumulative incidence (CI) of neutrophil engraftment at day 60 was 61%, after a median time of 22 days (range 12-55 days) and the CI of platelet engraftment at day 60 was 42%, after a median time of 41 days (range 16-125 days). CI of neutrophil engraftment was only 39% for patients with CML. Nucleated or CD34+ cell dose, number of HLA disparities, bank origin or other patient, disease or transplant-related factors were not associated with engraftment. Techniques of CB thawing, CB unit transportation or cell viability were not analyzed. Only experience of centers (more than 30 UCBT performed) was associated with improved engraftment rate (p=0.05). CI of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 19% and of chronic GVHD only 5% at 3 years. CI of non-relapse related mortality (NRM) was 41%. In a multivariate analysis, factors significantly associated with a higher NRM were patients older than the median age (51% vs. 32% for younger patients, p=0.05), and CD34+ cell dose lower than 1×105/kg (54% vs. 25% P=0.002). At 3 years, the CI of relapse or progression was 20%, and the estimated progression-free survival (PFS) was 36%. In a multivariate analysis, the most important factors associated with a decreased PFS rate were advanced disease status (28% vs. 46% for patients in remission, p=0.001), and a CD34+ cell dose lower than 1×105/kg (21% vs. 42%, p=0.04). At 3 years, estimated overall survival was 41%. In conclusion, UCBT in Brazil seems to be associated with lower engraftment rates as compared to the published experience from other countries. Other factors such as CB unit transportation, CB thawing and cell viability may be analyzed in order to explain the lower engraftment rates. Nevertheless, use of HLA-mismatched UCBT is a valuable alternative for patients with hematologic malignancies in Brazil who lack an HLA-matched related or unrelated donor. UCB units with a higher CD34+ cell count and transplants performed for patients in remission may improve outcomes.

Disclosures:
No relevant conflicts of interest to declare.