Risk Factors Analysis of Outcomes of Related Cord Blood Transplantation in Children with Hematological Malignancies.
Authors: Teira Pierre , Rocha Vanderson , Locatelli Franco , Pasquini Ricardo , Socie Gerard , Bertrand Yves , Fagioli Franca , Messina Chiara , Abecasis Manuel , Gerard Michel , Pihkala Ulla , Ionescu Irina , Garnier Federico , Gluckman Eliane 
Published: October 2019

Abstract
Overall survival of HLA identical bone marrow are comparable to umbilical cord blood transplantation (RCBT) in children with malignant and non-malignant disorders, however there is no data analysing risk factors of outcomes in a large series of children with malignancies given a RCBT. Thus, we have studied 128 RCBT performed from 1990 to 2005 and reported to Eurocord. The median age was 5 years (1–20 y); weight 19kg (8–56); and the median follow up was 55 months (2–162). Most of the children had leukemia [ALL (n=73), AML or MDS (n=33) CML (n=13)] and 9 children had other malignancies (4 non-Hodgkin lymphoma, 4 solid tumors,1 histiocytosis). Previous autologous transplant was given to 11%. At transplant, 22 children (17%) were transplanted in early stage of the disease; 58 (45%) in intermediate and 47 (37%) in more advanced phase. Median time from diagnosis to transplantation was 19 months (4–105). The donor was HLA identical in 104 cases (81%) and HLA incompatible in 24 cases (1 antigen=3, 2 ag=10, 3 ag=11). TBI based regimen was used in 52% and as GVHD prophylaxis CSA alone in 59%. The median number of nucleated cells at collection was 4.8x107/kg (1–19x107) and at infusion was 4x107/kg (0.6–18). Most of cord blood units were banked at the local institution where the transplantation took place.
Results: median days of neutrophils and platelets recovery were 23 (8–49) and 38 (12–165) days, respectively. Estimate probability of neutrophils recovery at day 60 was 89±3% and 180-day platelet recovery was 81%. In multivariate analysis for neutrophil recovery, HLA identity was the most important factor associated with increased probability of recovery (93%vs 72%, adjusted p=0.004). There was a trend of better recovery for patients receiving a higher cell dose (90%vs 85%, adjusted p=0.06). Acute GVHD (II-IV) was observed in 24 patients (II=23, III=5, IV=2). HLA compatibility and higher cell dose were associated with decreased incidence of acute GVHD. In fact children receiving an HLA incompatible graft had an incidence of 46% compared to 17% of the remainders (p<0.001). Chronic GVHD was observed in 12% of patients at risk. At 5 years relapse incidence was 44% for patients transplanted in early phase of the disease, 54% in intermediate and 65% for those in advanced phase (p=0.04). At 5 year transplantation related mortality was 21%, overall survival was 48% and disease-free survival (DFS) was 40%. In a multivariate analysis for DFS, HLA compatibility (p<0.001), female gender (p=0.03), younger children (<5 years)(p=0.05) and children transplanted in remission (p=0.02) were factors associated with increased DFS. In fact, 5 y-DFS of children transplanted with an HLA compatible donor was 46% compared to 13% in those transplanted with an incompatible relative. In conclusion, with these promising results, banking of a related HLA identical unit should be encouraged when possible. HLA compatibility plays an important role for neutrophils recovery, GVHD and DFS after RCBT.