Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome.
OBJECTIVE
Hurler syndrome is a debilitating genetic disease with a typical life span of 5 to 8 years. Early hematopoietic stem cell transplantation (HSCT) mitigates disease symptoms and improves survival. However, morbidity and mortality associated with HSCT can limit its success. We describe the initial experience with combined use of enzyme replacement therapy (ERT, laronidase) and HSCT in Hurler syndrome.


METHODS
Thirteen transplants were performed in 12 patients. ERT was given at a standard dose of 0.58 mg/kg per week. Transplant conditioning regimen and donor graft source were determined by institutional protocol.


RESULTS
The median age at initiation of ERT was 12 months (range, 8 to 18 months). The median duration of pre-HSCT ERT was 12 weeks (range, 4 to 28). All but 1 patient tested showed decrease in urinary GAG excretion during ERT. ERT infusion-related toxicity was limited to mild reactions. Development of antibodies to laronidase did not correlate with infusion reactions or responses in urinary GAG excretion. ERT was given for a median of 7 weeks (range, 3 to 20) after HSCT. After transplantation, eight patients demonstrated complete donor engraftment and four suffered graft failure. Two patients required ventilator support and three developed acute GVHD. Eleven of the 12 patients are surviving with a median follow-up of 3 months (range, 1 to 7 months).


CONCLUSIONS
In children with Hurler syndrome, ERT with HSCT is feasible and well tolerated. Development of antibodies against exogenous enzyme does not appear to correlate with infusion reactions or response to ERT. A prospective study is needed to determine the effect of concomitant ERT on transplant outcomes.
Grewal
Satkiran S
SS
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Wynn
Robert
R
Abdenur
Jose E
JE
Burton
Barbara K
BK
Gharib
Maged
M
Haase
Claudia
C
Hayashi
Robert J
RJ
Shenoy
Shalini
S
Sillence
David
D
Tiller
George E
GE
Dudek
Martha E
ME
van Royen-Kerkhof
Annet
A
Wraith
James E
JE
Woodard
Paul
P
Young
Guy A
GA
Wulffraat
Nico
N
Whitley
Chester B
CB
Peters
Charles
C
D000208:Acute Disease; D003131:Combined Modality Therapy; D005260:Female; D006084:Graft Rejection; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007068:Iduronidase / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy*; D011994:Recombinant Proteins; D012121:Respiration, Artificial; D016896:Treatment Outcome
D011994:Recombinant Proteins; D007068:Iduronidase