Table 2.

Graft sources for HCT for PID

Graft	Patient subset	Transplant Features and Current Challenges
HLA-matched: genotypic related	SCID	No pre-HCT conditioning is needed to achieve T cell reconstitution. B cell reconstitution occurs in 25-30% of cases depending in part on genotype; other factors are probably also important but not well defined.
	Non-SCID	Immunosuppression and myeloablation are generally required, similar to HCT for non-PID, non-malignant indications. Full donor chimerism may be needed for some disorders to fully correct disease manifestations. Reduced toxicity regimens with mixed chimerism may be effective for some non-SCID PID. Further study is required.
Haplocompatible related with T cell depletiona	SCID: B+NK−	Without pre-HCT chemotherapy, donor T-cell engraftment is easily achieved, but donor B cells are unlikely to engraft and post-HCT B cell function may remain abnormal. Myeloablative chemotherapy increases the likelihood of both T and B cell reconstitution, but entails risks of short and long term sequelae especially in young infants and those presenting with severe infections. A haplocompatible related (parental) donor is readily available.
	SCID: B+/− NK+	Without pre-HCT immunosuppression, graft rejection may be increased unless maternal engraftment is present and the mother is used as the donor. With immunosuppression, T but not B cell immunity is likely to be restored. Myeloablation may yield more durable donor T-cell engraftment and an improved rate of donor B cell engraftment, but entails risks of short and long term sequelae especially in young infants and those presenting with severe infections.
	Non-SCID	Immunosuppression and myeloablative chemotherapy are required. Higher transplant related mortality with the use of haplocompatible donors and increasing availability of unrelated donor sources makes this option less desirable.
Closely matched unrelated donor (MUD)	SCID	Most HCT from unrelated donors use myeloablative conditioning regimens, which entail risks of increased transplant related mortality and late effects. It remains to be determined if fully allele matched unrelated donor HCT can be successful without any conditioning. However, GVHD is a greater risk than with matched related donors and the search process can take weeks to months.
	Non-SCID	High resolution allele matched unrelated donors appear to compare favorably to matched related donors, including rate of engraftment and extent and durability of immune reconstitution. High dose chemotherapy is required and acute and chronic GVHD likely. Clinical trials to assess survival as well as other outcomes are needed.
Unrelated cord blood (CB)	SCID	To date data are limited. High cell dose can usually be achieved and cells are readily available once a unit isx identified. High dose chemotherapy conditioning is usually given. Further studies are needed to define optimal conditioning regimens.
	Non-SCID	High dose chemotherapy is required. Risk of graft failure/rejection is 10-15%. Booster or second transplants from the same donor are not possible. Clinical trials to assess survival as well as other outcomes are needed.

^aT-cell depletion of the graft may be accomplished by selection of the soy bean agglutinin (SBA) negative, sheep erythroid (E) - rosette negative fraction,⁷ or by use of the Isolex or Miltenyi CD34+ cell selection devices with or without negative depletion of CD3+ cells.^12-14 To date, there has been no formal comparison between the different processing regimens, which result in different cell populations being infused and may have different outcomes.