Early SCID identification improved survival after HSCT
Patients with severe combined immunodeficiency demonstrated improved survival when they underwent hematopoietic-cell transplantation at a younger age, before the onset of infection or after the infection resolved, according results of a retrospective analysis.
“Survival is much, much better if infants undergo transplant before they turn 3.5 months old and before they contract any [severe combined immunodeficiency (SCID)]-related infections,” Sung-Yun Pai, MD, a pediatric hematologist-oncologist at Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, said in a press release. “The best way to identify patients that early when there is no family history of SCID is through newborn screening.”
Pai and colleagues with the Primary Immune Deficiency Treatment Consortium evaluated data from 240 infants with SCID who underwent HSCT between 2000 and 2009.
Seventy-four percent (95% CI, 68-79) of patients survived 5 years. Thirty-nine percent of deaths were due to infections and 37% were due to pulmonary complications. Most deaths occurred within the first year after transplantation.
Five-year OS was highest among patients who underwent HSCT when aged 3.5 months or younger (94%; 95% CI, 85-98). Survival rates also were favorable among those aged older than 3.5 months who underwent HSCT before the onset of infection (90%; 95% CI, 67-98) and those whose infections resolved before transplantation (82%; 95% CI, 70-90).
Five-year OS among infants aged older than 3.5 months who had an active infection at the time of HSCT was 50% (95% CI, 39-61).
Donor type was significantly associated with survival, according to researchers. Ninety-seven percent of patients with sibling donors survived 5 years, whereas 79% of those with mismatched related donors who received T-cell–depleted grafts without conditioning survived 5 years (P=.07). The 5-year survival rate was 66% among patients who underwent conditioning with mismatched related donors (P=.008), 58% among cord blood recipients (P=.01) and 74% among recipients of other grafts (P=.01).
Patients with matched sibling donors also were significantly more likely to achieve CD3-positive T-cell count >1,000 mm3 and independence from IV immunoglobulin (IVIG) therapy at 2 to 5 years compared with infants with mismatch related (CD3-positive T-cell count, P=.01; IVIG therapy, P˂.001) and other related or unrelated donors (CD3-positive T-cell count, P=.04; IVIG therapy, P=.02).
Myeloablative or reduced-intensity conditioning with a mismatched related or alternative donor was associated with CD3-positive T-cell recovery (P=.005), B-cell chimerism (P˂.001), normal immunoglobulin levels (P˂.001) and independence from IVIG therapy (P˂.001) compared with immunosuppression or no conditioning.
“This confirms that transplants for SCID work well in very young children, but it also shows that any child with this disease can be treated with a high likelihood of a cure with a transplant from a parent or unrelated donor, not just a matched brother or sister,” Richard J. O’Reilly, MD, chair of the pediatric department and pediatric bone marrow transplant service at Memorial Sloan Kettering Cancer Center, said in the press release. “Irrespective of the transplant approach used, if the child is transplanted early — without infection — you will have an extraordinarily good result.”
Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.