Post-Transplantation Late Complications Increase Over Time for Patients With SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) Landmark Study

Investigate long-term outcomes of hematopoietic cell transplantation (HCT) as treatment of patients with severe combined immunodeficiency (SCID).This study included 399 patients from 32 PIDTC centers who had survived ≥2 years since HCT for SCID. Inclusion criteria required that patients remained alive, had not been lost to follow-up, and had not required a second subsequent cellular therapy for at least 2 years after their initial transplant.This was a retrospective, multicenter natural history study evaluating for chronic and late effects (CLE) after HCT. CLE were defined as either conditions that presented at any time before 2 years from HCT and remained unresolved (chronic) or new conditions that developed past 2 years after HCT (late), including autoimmune, cardiac, dental, endocrine, gastrointestinal, hepatic, musculoskeletal, neurodevelopmental, neurologic, pulmonary, and neoplastic.The cumulative index of CLE increased over time from 25% at year 2 to 42% by year 15 status post HCT. The most prevalent categories of CLE among these patients were neurologic (9%), neurodevelopmental (8%), and dental (8%). Cumulative indices of these individual CLE increased over time as well. Malignancies occurred in 2% of the patients, with lymphoma or lymphoproliferative disease and nonmelanoma skin malignancies being most common. The cumulative index of CLE was higher in patients who had any infection before HCT, regardless of whether the infection was active or resolved at the time of HCT. Age at time of transplantation did not affect development of CLE. Use of either myeloablative or reduced intensity chemotherapy-based conditioning pre-HCT was associated with a decreased-height z-score at 2 to 5 years after HCT, as well as increased endocrine and dental CLE. Survival 2 to 15 years after HCT was 90%, but any CLE was associated with increased risk of late death.HCT as treatment of SCID can be associated with extensive morbidity, adversely impacting overall survival. Poor immune reconstitution and/or the presence of CLE were particularly associated with late death.The advent of newborn screening has allowed for timely detection of SCID and, subsequently, more prompt definitive treatment with HCT. With increasing numbers of long-term survivors with SCID, this multicenter study demonstrates that implementing more specific survivor monitoring guidelines based on disease characteristics and treatment exposures will be beneficial to this growing population of patients.