OUTCOME OF UNRELATED DONOR BONE-MARROW TRANSPLANTATION IN 40 CHILDRENWITH HURLER-SYNDROME

Long-term survival and improved neuropsychological function have occur red in selected children with Hurler syndrome (MPS I H) after successf ul engraftment with genotypically matched sibling bone marrow transpla ntation (BMT). However, because few children have HLA-identical siblin gs, the feasibility of unrelated donor (URD) BMT as a vehicle for adop tive enzyme therapy was evaluated in this retrospective study. Forty c onsecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation foll owed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probabi lity of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patient s received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two chi ldren have mixed chimeric grafts, and five children have autologous ma rrow recovery. The BM cell dose was correlated with both donor engraft ment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of e ngraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patien ts receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are est imated to be alive at 3 years (P = .05). The mental developmental inde x (MDI) was assessed before BMT. Both baseline and post-BMT neuropsych ological data were available for 11 engrafted survivors. Eight childre n with a baseline MDI greater than 70 have undergone URD BMT (median a ge, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have h ad BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children ar e acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowi ng in their learning process. For children with a baseline MDI less th an 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follo w-up indicated that two children have shown deterioration in their dev elopmental skills. the remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude t hat MPS I H patients with a baseline MDI greater than 70 who are engra fted survivors following URD BMT can achieve a favorable long-term out come and improved cognitive function. Future protocols must address th e high risk of graft rejection or failure and the impact of GVHD in th is patient population. (C) 1996 by The American Society of Hematology.