Outcomes Of Transplantation Using A Various Cell Source In Children With Hurlers Syndrome After Myelo-Ablative Conditioning. An Eurocord-EBMT-CIBMTR Collaborative Study

Hurlers 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), if performed early halts disease progression and prolongs life. Graft-failure and mixed-chimerism (40-50%) limit the success of SCT in HS. Various cell sources including unrelated cord blood have been used over the last decades. However, impact of various cell sources (Matched Sibling donor; MSD, unrelated donor; UD, unrelated cord blood; uCB and T-cell depleted UD; TCDud) on outcomes of SCT in HS is not well studied. We have analyzed 258 HS children that received a SCT after a myelo-ablative conditioning regimen from 1995 to 2007 and were reported to EUROCORD, EBMT or CIBMTR. Median age at SCT was 16.7 (2-228) months, and median follow up was 57 (1.3-140) months. The donors were MSD (n=37; 14%), UD (n=52; 21%), uCB (n=116; 44%), TCDud (n=53; 21%). All but 8 patients, received a Busulfan-based myeloablative regimen. All patients receiving an unrelated donor and 8 MSD received ATG (n=207) or Campath (n=21). Overall neutrophil recovery was 91+/-3% at day 60. Overall acute-GvHD (grade II-IV) was observed in 26%, while chronic-GvHD was seen in 12+/-3% at 5 years. Five years overall survival (OS) and disease and event free survival (EFS) were 74% and 64%, respectively. For OS at 5 years, an age of <20months at SCT was associated with a higher survival (p=0,04). OS was higher after MSD (92%), compared to the other sources UD (76%; p=0.078), uCB (74%; p=0,038) and TCDud (64%; p=0,007). EFS at 5 years was similar between MSD (81%), MUD (69%; p=0,148) and uCB (67%; p=0,11) but lower after TCDud (38%; p<0.001). Of those who were “alive and engrafted” mixed-chimerism (>5% recipient) at latest follow up time point (median 57mths: 6-140) was found in 21%. The highest rate of full donor chimerism was found in uCB (93%), compared to 73% in MSD, 64% in UD and 75% in TCDud. Normal enzyme levels at latest follow up time point were found in all (100%) of the uCB, in 53% of MSD, in 74% of UD and in 75% of TCDud recipients. Outcomes following SCT is HS are encouraging. Younger age at SCT is a predictor for higher OS. Regarding OS, MSD do better compared to UD and uCB, but no difference was found for EFS. TCDud is a predictor for lower OS/EFS. uCB leads to higher donor-chimerism levels and enzymes which is suggested to have a positive impact on the long term outcomes.