Pretransplant infection associated with inferior survival after TCRαβ/CD19-depleted haploidentical HSCT in pediatric nonmalignant disorders.

BACKGROUND AND AIMS: TCRαβ/CD19-depleted haploidentical hematopoietic stem cell transplantation (HSCT) is associated with favorable outcomes in pediatric nonmalignant disorders when performed in clinically stable patients receiving adequate conditioning. Outcomes in patients transplanted in the setting of active infection remain poorly defined. To evaluate the impact of pretransplant infection on outcomes after TCRαβ/CD19-depleted haploidentical HSCT in pediatric nonmalignant disorders.

METHODS

We retrospectively analyzed 36 pediatric patients with nonmalignant disorders who underwent haploidentical HSCT using TCRαβ/CD19-depleted grafts at a single center between 2012 and 2021. Diagnoses included inborn errors of immunity (n = 22, including 17 with severe combined immunodeficiency), familial hemophagocytic lymphohistiocytosis (n = 9), and bone marrow failure syndromes (n = 5). Twenty-two patients (61%) had active infection at transplantation.

RESULTS

Engraftment occurred in 26 patients (72%). The cumulative incidence of grade II-III acute graft-versus-host disease was 30%, and chronic graft-versus-host disease occurred in 19%. Fourteen patients died during follow-up. One-year overall survival was 56.1% (95% CI, 41.2-76.6%), with a median follow-up of 20 months. No deaths occurred beyond the first year after transplantation. Infection was the most common cause of death. Survival was significantly higher in patients without infection at transplantation compared with those with active infection (91.7% versus 33%, P = 6.5 × 10⁻⁴). Most graft failures occurred in patients who underwent transplantation with reduced-intensity or no conditioning because of severe infection.

CONCLUSIONS

Pretransplant infection is strongly associated with inferior survival after TCRαβ/CD19-depleted haploidentical HSCT in pediatric nonmalignant disorders. These findings emphasize the importance of infection control, timing of transplantation, and the ability to deliver adequate conditioning.