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Outcome of unrelated donor bone marrow transplantation in 40 children with
Hurler syndrome
C Peters, M Balthazor, EG Shapiro, RJ King, C Kollman, JD Hegland, J Henslee- Downey, ME Trigg, MJ Cowan, J Sanders, N Bunin, H Weinstein, C Lenarsky, P Falk, R Harris, T Bowen, TE Williams, GH Grayson, P Warkentin, L Sender, VA Cool, M Crittenden, S Packman, P Kaplan and LA Lockman
Department of Pediatrics University of Iowa, Iowa City 52242, USA.
Long-term survival and improved neuropsychological function have occurred
in selected children with Hurler syndrome (MPS I H) after successful
engraftment with genotypically matched sibling bons marrow transplantation
(BMT). However, because few children have HLA-identical siblings, the
feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme
therapy was evaluated in this retrospective study. Forty consecutive
children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received
high-dose chemotherapy with or without radiation followed 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 probability of grade II to IV
acute graft-versus-host disease (GVHD) was 30%, and the probability of
extensive chronic GVHD was 18%. Eleven patients received a second URD BMT
because of graft rejection or failure. Of the 20 survivors, 13 children
have complete donor engraftment, two children have mixed chimeric grafts,
and five children have autologous marrow recovery. The BM cell dose was
correlated with both donor engraftment 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 engraftment. 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 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and
24% are estimated to be alive at 3 years (P = .05). The mental
developmental index (MDI) was assessed before BMT. Both baseline and
post-BMT neuropsychological data were available for 11 engrafted survivors.
Eight children with a baseline MDI greater than 70 have undergone URD BMT
(median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children
have had BMT too recently for developmental follow-up. Of the remaining
six, none has shown any decline in age equivalent scores. Four children are
acquiring skills at a pace equal to or slightly below their same age peers;
two children have shown a plateau in learning or extreme slowing in their
learning process. For children with a baseline MDI less than 70 (median
age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that
two children have shown deterioration in their developmental skills. The
remaining three children are maintaining their skills and are adding to
them at a highly variable rate. We conclude that MPS I H patients with a
baseline MDI greater than 70 who are engrafted survivors following URD BMT
can achieve a favorable long-term outcome and improved cognitive function.
Future protocols must address the high risk of graft rejection or failure
and the impact of GVHD in this patient population.
Volume 87,
Issue 11,
pp. 4894-4902,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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