Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic deterioration and early death. Allogeneic bone marrow transplantation (BMT) ameliorates or halts this course. The Storage Disease Collaborative Study Group was formed to evaluate the effectiveness and toxicity of BMT. Effectiveness was defined as engrafted survival with continuing cognitive development. Fifty-four patients deficient in leukocyte α-l-iduronidase enzyme activity (median age, 1.8 years; range, 0.4 to 7.9) received high-dose chemotherapy with or without irradiation and BMT from HLA-genotypically identical sibling (GIS) or HLA-haploidentical related (HIR) donors between September 16, 1983 and July 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 was 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 probability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marrow engraftment. The baseline Mental Developmental Index (MDI) was examined both for children less than and greater than 24 months of age at BMT. Children transplanted before 24 months had a mean baseline MDI of 78, while those transplanted after 24 months had a mean baseline MDI of 63 (P = .0002). Both baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted survivors. Of 14 patients transplanted before 24 months of age, nine demonstrated developmental trajectories that were normal or somewhat slower than normal. In contrast, of 12 patients transplanted after 24 months of age, only three showed developmental trajectories that were normal or somewhat slower than normal (P = .01). For children with a baseline MDI greater than 70, there was a significant correlation between the MDI at follow-up study and leukocyte α-l-iduronidase enzyme activity (P = .02). Children were more likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte α-l-iduronidase enzyme activity. Children who developed acute GVHD of grade II or worse had significantly poorer cognitive outcomes (P < .009). No difference in the post-BMT MDI was observed between patients whose preparative therapies did (n = 10; radiation dose, 300 to 1,400 cGy) or did not (n = 16) include radiation. We conclude that MPSIH patients, particularly those less than 24 months of age with a baseline MDI greater than 70, can achieve a favorable long-term outcome with continuing cognitive development and prolonged survival after successful BMT from a related donor with homozygous normal enzyme activity.

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When Metchnikoff defined the process of phagocytosis in 1884 (1, 2), he conceded to serum the minor role of an dement that merely modified the phagocyte. However, in 1903 Wright and Douglas clearly established that phagocytosis of pathogenic bacteria could not occur without serum; that this effect was achieved by modification of the microorganism rather than the phagocyte; and that immunity developed in the serum, not the leukocyte (3, 4). Whether this serum effect was accomplished by specific antibody alone or by antibody acting in conjunction with a nonspecific, heat-labile serum activity, namely complement, was not dear until the experiments of Ward and Enders in 1933. They demonstrated that ingestion of pneumococci could occur slowly in the presence of heated immune serum; however, the addition of small amounts of fresh, nonimmune serum markedly enhanced the rote of ingestion (5).The heat-labile factor or factors necessary for optimal phagocytosis of bacteria have not been precisely identified. On the basis of their own and other available experimental data, Boyden et al. found it impossible to define the role of thermolabile factors as opsonins and pointed out the need for a means of accurately measuring phagocytosis of bacteria (6). The present report describes a spectrophotometric method of measuring bacterial phagocytosis and its application to demonstrate that the first four components of human complement and two serum cofactors are necessary for the optimal phagocytosis of pneumococci by human leukocytes.