Risk Factors Analysis of Outcomes of Related Cord Blood Transplantation in Children with Hematological Malignancies.

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.