HURLER-SYNDROME - II - OUTCOME OF HLA GENOTYPICALLY IDENTICAL SIBLINGAND HLA-HAPLOIDENTICAL RELATED DONOR BONE-MARROW TRANSPLANTATION IN 54 CHILDREN

Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic deterioration and early death. Allogeneic bone marrow tran splantation (BMT) ameliorates or halts this course. The Storage Diseas e Collaborative Study Group was formed to evaluate the effectiveness a nd toxicity of BMT. Effectiveness was defined as engrafted survival wi th continuing cognitive development. Fifty-four patients deficient in leukocyte alpha-L-iduronidase enzyme activity (median age, 1.8 years; range, 0.4 to 7.9) received high-dose chemotherapy with or without irr adiation and BMT from HLA-genotypically identical sibling (GIS) or HLA -haploidentical related (HIR) donors between September 16, 1983 and Ju ly 14, 1995; all children were included in this report. Thirty-nine of 54 patients (72%) engrafted following the first BMT. The probability of grade II to IV acute graft-versus-host disease (GVHD) at 100 days w as 32% for GIS and 55% for HIR patients. The probability of extensive chronic GVHD was 0% for GIS and 24% for HIR patients. The actuarial pr obability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marro w engraftment. The baseline Mental Developmental Index (MDI) was exami ned both for children less than and greater than 24 months of age at B MT. Children transplanted before 24 months had a mean baseline MDI of 78, while those transplanted after 24 months had a mean baseline MD( o f 63 (P = .0002). Both baseline and post-BMT neuropsychologic data wer e available for 26 of 30 engrafted survivors. Of 14 patients transplan ted before 24 months of age, nine demonstrated developmental trajector ies that were normal or somewhat slower than normal. In contrast, of 1 2 patients transplanted after 24 months of age, only three showed deve lopmental trajectories that were normal or somewhat slower than normal (P = .01). For children with a baseline MDI greater than 70, there wa s a significant correlation between the MDI at follow-up study and leu kocyte alpha-L-iduranidase enzyme activity (P = .02). Children were mo re likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte (alpha-L-iduronidase enzyme activity. Children who developed acute GVH D of grade II or worse had significantly poorer cognitive outcomes (P < .009). No difference in the post-BMT MDI was observed between patien ts whose preparative therapies did (n = 10; radiation dose, 300 to 1,4 00 cGy) or did not (n = 16) include radiation. We conclude that MPSIH patients, particularly those less than 24 months of age with a baselin e MDI greater than 70, can achieve a favorable long-term outcome with continuing cognitive development and prolonged survival after successf ul BMT from a related donor with homozygous normal enzyme activity. (C ) 1998 by The American Society of Hematology.