Bone marrow transplantation in hurler syndrome: Factors predictive of favorable outcome

Untreated Hurler syndrome (MPSIH) patients experience progressive neurologic deterioration and early death. Allogeneic bone marrow transplantation (BMT) ameliorates or halts this course. The Storage Disease Collaborative Study Group has evaluated the effectiveness of BMT. Effectiveness is defined as survival with continuing cognitive development. One hundred six (106) children with MPSIH underwent BMT using HLA-genotypically identical (GIS), non-genotypically identical related (NGIR), or unrelated (UR) donors (median follow-up, UR: 0.5 yrs, GIS: 6.7 yrs, NGIR: 4.4 yrs, UR: 5.4 yrs). Donor pts/BMTs aGVHD/cGVHD Engraft Survival E+S FO UR 12/13 16%/0% 83% 67% 67% 67% GIS 28/29 32%/0% 80% 82% 75% 46% NGIR 26/27 55%/24% 65% 56% 35% 27% UR 40/51 30%/18% 63% 49% 31% 25% UR (MN): 5/94 to present, includes 2 cord blood transplants, 1 pt with 2nd BMT, busulfan 320 mg/m, cyclophosphamide 120 mg/kg, TBI 750 cGy (I fraction), ATG/methylprednisolone, elutriated marrow; GIS: 9/83 to 5/95, 2 deaths pre-BMT, 3 pts with 2nd BMTs; NGIR: 4/85 to 7/95, I pt with 2nd BMT; UR: 1/89 to 5/94, 11 pts with 2nd BMTs (BLOOD 1996; 87:4894); aGVHD/cGVHD: acute GVHD > grade Il/extensive chronic GVHD: E+S: engrafted survival; FO: favorable outcome (alive, engrafted, continuing cognitive development) The likelihood of a favorable outcome following BMT in MPSIH patients is significantly enhanced if: I ) BMT occurs before 24 months 2) baseline pre-BMT mental developmental index (MDI) is greater than 70, 3) complete engraftment occurs, 4) the donor has homozygous normal alpha-L-iduronidase enzyme activity. We conclude that MPSIH patients, particularly those <24 months of age with a baseline MDI >70, can achieve a favorable long-term outcome with continuing cognitive development and prolonged survival after successful BMT from a donor with normal alpha-L-iduronidase enzyme activity.