Hematopoietic stem cell transplantation (HSCT) remains the treatment of choice for children with myelodysplastic syndromes (MDS). Umbilical cord blood (UCB) represents an alternative source of hematopoietic stem cells for transplantation in children without a HLA-matched sibling. We examined risk factors influencing outcomes after UCB transplantation (UCBT) in 70 children (40 males and 30 females; median age 7 years, range 0.8–18) with MDS reported to the European Working Group of MDS in Childhood, the Center for International Blood and Marrow Transplant Research or the Eurocord-European Blood and Marrow Transplant Group. Excluded were patients who had received prior autologous/allogeneic HSCT and those with Down syndrome, Fanconi anemia, or MDS that evolved to AML prior to HSCT. Patients had refractory cytopenia (RC, n=31), refractory anemia with excess blasts (RAEB, n=30), and RAEB in transformation (RAEB-t, n=9). All patients received a single UCB unit and myeloablative preparatory regimen. Karyotype analysis (available for 68 of 70 patients) was normal in 22 patients, while the remaining 46 had cytogenetic abnormalities, the most frequent being monosomy 7 (n= 23). In all pairs but one, donor-recipient histocompatibility was determined by serology (low-resolution typing) for HLA-A and -B and allele-level typing for DRB1. UCB units were HLA matched (A, B, DRB1) in 4 cases, 1-locus, 2-loci and 3-loci mismatched in 34, 26 and 5 cases, respectively. The day-60 probability of neutrophil recovery was 76%; in multivariate analysis, transplantation of HLA matched or 1-locus mismatched UCB, irradiation-containing preparatory regimen, cell dose ≥ 6x107/kg (pre-cryopreservation) and monosomy 7 were associated with faster neutrophil recovery. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 30% (95% CI, 20–41). The 3-year cumulative incidence of chronic GVHD was 23% (95%CI 14–33). Five of 16 patients with chronic GVHD had limited and 11 extensive chronic GVHD. Twenty-nine patients died from transplantation-related complications, the 3-year cumulative incidence of transplantation-related mortality (TRM) was 41% (95% CI 29–52). Three deaths were related to GVHD. In multivariate analysis, TRM was lower when transplants were performed after 2001 (HR 0.41, 95%CI 0.20–0.84, p=0.015). Thirteen patients had recurrent disease and 11 were dead at last follow up. No variable predicted disease recurrence. With a medium follow-up of 39 months (range 10 – 105), the 3-year probability of disease-free survival (DFS) for the entire cohort was 39%; it was 50% when transplantation was performed after 2001 compared to 27% in the earlier period (p=0.02). After 2001, patients received UCB containing higher cell doses and the interval from diagnosis to transplantation was shorter. The 3-year DFS was 61% for the 23 patients with monosomy 7 compared to 30% for patients with other karyotypes (p=0.042). In multivariate analysis, year of transplantation (prior to 2001) and cytogenetic abnormalities other than monosomy 7 were independent risk factors predicting treatment failure, HR 2.38, (95% CI: 1.14–5.0, p=0.02) and HR 2.04,(95% CI: 1.11–3.70, p=0.02), respectively. The 3-year DFS was not influenced by MDS variant. Given the relatively small sample size the influence of MDS variant on transplant-outcome requires validation in a larger series. These data indicate that UCBT is an acceptable alternative in children with MDS without a HLA-matched related or unrelated adult bone marrow donor. The results of UCBT have improved in recent years and monosomy 7 does not confer an unfavourable outcome.

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