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Hurler Syndrome: II. Outcome of HLA-Genotypically Identical
Sibling and HLA-Haploidentical Related Donor Bone Marrow
Transplantation in Fifty-Four Children
Charles Peters,
Elsa G. Shapiro,
James Anderson,
P. Jean Henslee-Downey,
Martin R. Klemperer,
Morton J. Cowan,
E. Fred Saunders,
Pedro A. deAlarcon,
Clare Twist,
James B. Nachman,
Gregory A. Hale,
Richard E. Harris,
Marta K. Rozans,
Joanne Kurtzberg,
Guy H. Grayson,
Thomas E. Williams,
Carl Lenarsky,
John E. Wagner,
William Krivit, and
the members of The Storage Disease Collaborative Study
Group
From The Storage Disease Collaborative Study Group, Department of
Pediatrics, Division of Bone Marrow Transplant, University of
Minnesota, Minneapolis.
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  -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 -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
-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.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2601-2608
© 1998 by The American Society of Hematology.
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