Risk Factor Analysis of Outcomes after Unrelated Cord Blood Transplantation for Children with Hurler’s Syndrome. An Eurocord-Duke University Collaborative Study.

Hurler’s syndrome (HS), the most severe form of mucopolysaccharidosis type-I causes progressive deterioration of the central nervous system and death in childhood. Allogeneic-stem cell transplantation (SCT) before the age of two years halts disease progression and prolongs life. Graft-failure and mixed-chimerism (40–50%) limit the success of SCT for HS. Unrelated-cord blood transplants (UCBT) are suggested to be a good alternative option for bone marrow, however, little is known about risk factors for outcomes after UCBT for this disease. We have analyzed 93 HS children that received an UCBT from 1995 to 2007 and were reported to EUROCORD or transplanted at Duke University. Median age at UCBT was 1, 3 (0, 2–4) yrs, and median follow up was 24 (3–140) mths. The donor was HLA-identical (HLA-A and -B by low resolution and HLA-DRB1 by high-resolution) in 13 cases (16%) and incompatible in 67 cases (84%: most with 1 (54%) and 2(26%) HLA disparities). The median nucleated cell dose/kg and CD34+/kg at infusion were respectively 7.2 (2–22) x 10⁷ and 2, 3 (0, 5–17) x 10⁵. With the exception of 5 patients, all received a Busulfan/Cyclophosphamide (+Fludarabine: 6) regimen. All patients received ATG or Campath (4).

Results: Median days to neutrophil and platelet recovery were 22 (10–46) and 35 (13–82) days, respectively. Mixed-chimerism was found in only 6%. All patients had normal enzyme levels after engraftment. In multivariate analyses for neutrophil recovery, a CD34+-dose of >2.3x10⁵/kg (HR=2.0; p= 0.015) was associated with increased probability of recovery. Acute-GvHD (grade II-IV) was observed in 27%, while chronic-GvHD was seen in 10% at 2 years. Two years overall survival (OS) and disease free survival were 78% and 70%, respectively. For 2 years OS, time from diagnosis to UCBT more than 6 months was associated with increased risk of death (6% for those children transplanted earlier and 30% for those transplanted later: p=0,04). Transplantation improved somatic features of HS. In conclusion, outcomes following UCBT for Hurler’s syndrome are encouraging. UCB appears to be a good alternative allogeneic stem cell source to transplant children with HS. Earlier transplantation and higher cell dose are associated with better outcomes after UCBT for HS patients.