PURPOSE OF THE STUDY.
To evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency (SCID) treated in North America between 2000 and 2009 based on data collected by the Primary Immune Deficiency Treatment Consortium.
Two hundred forty infants with SCID treated with HSCT at 25 centers during this 10-year period.
This was a retrospective study based on data entry into defined forms through the Primary Immune Deficiency Treatment Consortium. Each patient entry was reviewed by 3 content experts and classified as eligible versus not eligible on the basis of defined criteria required to meet the diagnosis of SCID. Transplant information was provided in terms of age at transplant, comorbidities at the time of transplant, donor source, posttransplant course, and immunologic status during follow-up.
Survival at 5 years, freedom from requiring immunoglobulin replacement therapy, circulating T-cell numbers, and plasma immunoglobulin A recovery were more likely using matched sibling donors that alterative donor sources. Despite those differences, and regardless of the donor source in infants receiving transplants before 3.5 months of age, the survival rate was 94% and among older infants transplanted before developing infection, the survival rate was 90%. Importantly, in older infants who had a history of infection that had been effectively treated before transplantation, the overall survival rate was 82%. In contrast, older infants who were actively infected at the time of transplantation had a significantly reduced survival (∼50%).
The data from this study indicate that children with classic SCID diagnosed at birth before the onset of infection who receive transplants from mismatched related donors or unrelated donors of cord blood soon after diagnosis should have a 90% probability of survival with T-cell and variable B-cell immune reconstitution. Additional findings in this study included the observation that reduced intensity or myeloablative conditioning when donors were other than matched siblings was associated with improved T-cell counts and more consistent B-cell function. However, in patients with active infection, conditioning carries greater risk with inferior outcome.
This report confirms a previous report from a single institution that hematopoietic stem cell transplantation in young infants with SCID yields superior outcome. However, this data set also identifies infection as the major culprit in poor outcomes when transplanting SCID infants. The poor outcome associated with pretransplant conditioning in infected SCID infants raises the possibility of performing a sequential transplant first using donor cells without conditioning to provide T-cell reconstitution followed by a second transplant using a conditioning regimen to improve the likelihood of B-cell function. There remain a number of unanswered questions that likely will be forthcoming as this North American consortium continues to collect both retrospective and prospective data. Among these are the following: what is the role of genotype in the immune reconstitution, when should conditioning be considered, and what is the optimal approach to conditioning when required? Overall, the results of this study provide further impetus for the TREC-based newborn screening that identifies at-risk babies early in life affording them the opportunity for curative therapy with a high likelihood of successful immune reconstitution. This highly successful screening program is now being applied to almost 90% of all newborns in the United States.
- Copyright © 2015 by the American Academy of Pediatrics