NEW YORK (Reuters Health) - If performed before symptoms set in, transplantation of umbilical-cord blood from unrelated donors into infants with Krabbe’s disease results in improved neurologic outcomes with relatively mild sequelae, according to a report in the New England Journal of Medicine for May 19.
However, if treatment is delayed until after the baby becomes symptomatic, it’s not likely that the patient will benefit.
Krabbe’s disease involves failed myelination in the central and peripheral nervous system followed by rapid neurologic deterioration and death. It is an autosomal recessive disorder linked to a deficiency in the lysosomal enzyme galactocerebrosidase, where symptoms typically appear before 6 months of age.
Between 1998 and 2004, Dr. Maria L. Escolar, at the University of North Carolina at Chapel Hill, treated 11 newborns (ages 12 to 44 days) who had been diagnosed perinatally because of family history, and 14 diagnosed after symptom onset (ages 142 to 352 days).
Following myeloablative therapy they were transplanted with cord-blood from unrelated donors matched for at least four of six HLA antigens.
At follow-up until January 2005, all 11 presymptomatic patients had survived for a median of 36 months, the authors report. Repeated brain MRI scans showed normal progression of myelination and age-appropriate changes in signal intensity. Vision and hearing were unaffected, and except for areas influenced by gross motor development, their cognitive development was normal.
Only 6 of the symptomatic infants survived until 2005 (median 41 months). Outcomes for those treated after symptom onset were not significantly different from those of an untreated control group (n = 190). They exhibited a developmental level equivalent to that of a one-month-old infant, and subsequent MRI scans showed progressive brain atrophy and worsening hyperintense signal abnormalities in 12 of 13 patients.
Blood galactocerebrosidase activity was maintained at the levels measured in cord blood prior to transplantation in all surviving patients.
“The marked differences in outcome” between symptomatic and asymptomatic patients “have implications for decisions regarding the implementation of newborn-screening programs for lysosomal storage diseases,” Dr. Escolar’s group concludes.
As studies are designed to assess risky treatments for otherwise untreatable genetic diseases, “a major challenge to investigators and regulator and review agencies will be to maximize safety but also recognize the importance of including the very young, even those who are presymptomatic,” Dr. Kenneth I. Weinberg, from the University of Southern California in Los Angeles, remarks in an accompanying editorial.
Source: N Engl J Med 2005;352:2069-2081,2124-2126. [ Google search on this article ]
MeSH Headings:Cell Transplantation: Hematopoietic Stem Cell TransplantationCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
