Second malignancies after autologous hematopoietic cell transplantation in children

Abstract

Childhood autologous hematopoietic cell transplant (AHCT) survivors can be at risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1,487 pediatric AHCT recipients to investigate the incidence and risk factors for SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma (18%), CNS tumors (14%), and Wilms tumor (2%). Median follow-up was 8 years (range, <1–21 years). SMNs were reported in 35 patients (AML/MDS=13, solid cancers=20, subtype missing=2). The overall cumulative incidence of SMNs at 10 years from AHCT was 2.60% (AML/MDS=1.06%, solid tumors=1.30%). We found no association between SMNs risk and age, gender, diagnosis, disease status, time since diagnosis, or use of total body irradiation or etoposide as part of conditioning. Overall survival at 5-years from diagnosis of SMNs was 33% (95% CI, 16–52%). When compared to age- and gender-matched general population, AHCT recipients had 24 times higher risks of developing SMNs (95% CI, 16.0–33.0). Notable SMN sites included bone (N=5 SMNs, observed (O)/expected (E)=81), thyroid (N=5, O/E=53), breast (n=2, O/E=93), soft tissue (N=2, O/E=34), AML (N=6, O/E=266), and MDS (N=7, O/E=6603). Risks of SMNs increased with longer follow-up from AHCT. Pediatric AHCT recipients are at considerably increased risk for SMNs and need life-long surveillance for SMNs.