Articles review – July 2014

Three interesting studies examining outcome of haematopoietic stem cell transplantation (HSCT) for severe combined immunoderficiency (SCID) have been recently published:

Pai and colleagues from the Primary Immune Deficiency Treatment Consortium (PIDTC) have just published the first US-wide retrospective study of outcome for HSCT for patients with SCID transplanted between 2000-2009¹. This article is important for a number of reasons:

• It is the first North American-wide multi-centre study looking at outcome of HSCT for SCID.
• It analyses outcomes since 2000, and therefore is relevant in the ‘modern era’ of HSCT
• It is the first report documenting outcome of HSCT since the advent of Newborn Screening for SCID

As might be predicted, survival was best for those transplanted before 3 months of age who were infection-free. Interestingly, in those transplanted at an older age – survival was similar in those who had had infection, as long as it had cleared.

Dvorak and colleagues have published a joint PIDTC-IEWP study comparing outcomes of transplant for SCID patients using matched unrelated donor or matched sibling donor infusions². Although most patients undergoing unrelated donor HCST achieved donor T-cell engraftment, similar to that achieved for sibling donors, the estimated 5-year overall and event-free survival were worse for unrelated donor recipients with higher incidences of Grade II-IV acute and chronic GVHD. Matched sibling donor recipients were more likely to achieve B-cell reconstitution.

Finally, Hassan and colleagues³ report on a retrospective UK study to determine if SCID phenotypes indicate host permissiveness to donor cell engraftment following non-conditioned HSCT. A detailed analysis of T- and B-cell immune reconstitution and donor chimerism was compared between the NK+ and NK- forms of SCID in almost 80 patients. Survival was better in matched sibling donor/matched family donor transplants compared with alternative donors and better in NK- rather than NK+ SCID with superior long-term recovery of CD4 T-cell immunity.  Significantly more children with NK+ SCID required additional transplantation procedures.

1. Pai S-Y, Logan BR, Giffith LM et al. Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009. N Engl J Med 2014;371:434-46.
   Abstract
2. Dvorak C, Hassan A, Slatter MA, et al. Comparison of outcomes of hematopoietic stem cell transplant without chemotherapy conditioning using matched sibling and unrelated donors for treatment of SCID. J Allergy Clin Immunol 2014 (in press)
3. Hassan A, Lee P, Maggina P, et al. Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency. J Allergy Clin Immunol 2014;133:1660-6.
   Abstract