More Children With SCID Are Now Transplant Candidates Interview with:
Richard J. O’Reilly, MD
Memorial Sloan Kettering Cancer Center

Medical Research: What are the main findings of the study?
Dr. O’Reilly:

1.       In a comparison of the results of HLA-matched sibling transplants with other established transplant approaches, including T-cell depleted half-matched parental marrow grafts, unmodified transplants from matched unrelated donors and cord blood transplants in the current era (2000-2009), transplants from donors other than HLA-matched siblings had 5 year survival outcomes similar to those of matched siblings when applied to young infants (≤ 3.5 months of age) or infants of any age that were not infected at the time of transplants. Thus any child born with SCID can now be successfully transplanted.

2.       Active infection at the time of transplant significantly reduced chances of long-term survival for all infants except those who received transplants from HLA-matched siblings. Thus, infection is a dominant determinant of transplant outcome.  Control of treatable infections prior to transplant should be a major clinical objective.

3.       Treatment with chemotherapy containing busulfan significantly enhances the likelihood of recovering a normal ability to make antibodies and fosters better recovery of T-cells that provide cell mediated immunity, and may be an acceptable risk in uninfected infants. However, use of any chemotherapy prior to transplant in an infant who is infected, greatly decreases chances of survival. In infected patients who lack a matched sibling, T-cell depleted transplants from half matched related donors had the best outcomes.

Medical Research: Were any of the findings unexpected?

Dr. O’Reilly:
1.       The deleterious effect of any type of preparatory chemotherapy on the survival of infants infected at the time of a transplant from any donor other than a matched sibling. This was clearly detected in a comparison of the survival of infected infants who received half HLA-matched T-cell depleted marrow transplants with versus without conditioning, and is likely the basis of the poor results of matched unrelated marrow and cord blood grafts in infected children, since most of them also received chemotherapy in preparation for transplant. As reflected in this study, many transplant groups currently routinely employ conditioning for infants with SCID who receive transplants from donors other than a matched sibling. This study demonstrates the enhanced risk associated with this approach.

Medical Research: What should clinicians and patients take away from your report?

Dr. O’Reilly:
1.       The results of this study strongly underscore the importance of early diagnosis, prior to onset of infection. A newborn screening test is now performed in 21 states that can detect all types of SCID within days of birth. Such early diagnosis allows transplantation in healthy infants and can secure long-term survival with full or partial restoration of immunity in over 90% of affected infants.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. O’Reilly:
1.       Identification of those genetic variants of SCID for which conditioning is required for engraftment of transplants from non-sibling donors.
2.       Development of alternative, more targeted and less toxic therapeutic strategies for securing consistent engraftment and durable, complete recovery of both antibody and cell mediated immune systems in infants with SCID.


Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009

Sung-Yun Pai, M.D., Brent R. Logan, Ph.D., Linda M. Griffith, M.D., Ph.D., Rebecca H. Buckley, M.D., Roberta E. Parrott, B.S., Christopher C. Dvorak, M.D., Neena Kapoor, M.D., Imelda C. Hanson, M.D., Alexandra H. Filipovich, M.D., Soma Jyonouchi, M.D., Kathleen E. Sullivan, M.D., Ph.D., Trudy N. Small, M.D., Lauri Burroughs, M.D., Suzanne Skoda-Smith, M.D., Ann E. Haight, M.D., Audrey Grizzle, M.P.H., Michael A. Pulsipher, M.D., Ka Wah Chan, M.D., Ramsay L. Fuleihan, M.D., Elie Haddad, M.D., Ph.D., Brett Loechelt, M.D., Victor M. Aquino, M.D., Alfred Gillio, M.D., Jeffrey Davis, M.D., Alan Knutsen, M.D., Angela R. Smith, M.D., Theodore B. Moore, M.D., Marlis L. Schroeder, M.D., Frederick D. Goldman, M.D., James A. Connelly, M.D., Matthew H. Porteus, M.D., Ph.D., Qun Xiang, M.S., William T. Shearer, M.D., Ph.D., Thomas A. Fleisher, M.D., Donald B. Kohn, M.D., Jennifer M. Puck, M.D., Luigi D. Notarangelo, M.D., Morton J. Cowan, M.D., and Richard J. O’Reilly, M.D.

N Engl J Med 2014; 371:434-446July 31, 2014DOI: 10.1056/NEJMoa1401177


Last Updated on September 14, 2014 by Marie Benz MD FAAD