Secondary Neoplasm in Survivors of Childhood Hematological Malignancies-Systematic Review

Childhood cancers account for approximately 1-2% of all malignancies worldwide, with hematologic cancers representing about 35-40% of pediatric cases. Improved survival has brought increased recognition of both acute and long-term therapy-related complications, including secondary malignant neoplasms (SMNs). Survivors of pediatric hematologic malignancies face a lifelong risk of secondary malignant neoplasms (SMNs), which remain among the most severe late effects of therapy.

We conducted a PRISMA 2020-aligned systematic review of cohort and registry studies evaluating SMNs after childhood hematologic cancers. Databases searched included PubMed, Embase, Web of Science, Scopus, and Cochrane Library. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale; disagreements were resolved by a third reviewer.

Forty-three studies (>70,000 survivors, median follow-up 5-30+ years) were included. Standardized incidence ratios (SIRs) for secondary malignant neoplasms compared to the general population ranged from 2.0 to 6.0, with absolute excess risks (AERs) of approximately 10-40 per 10,000 person-years. Therapy-related acute myeloid leukemia occurred within 5-10 years, while solid secondary malignant neoplasms (breast, thyroid, central nervous system, sarcomas) emerged after 10-25 years. The highest risks for developing secondary malignant neoplasms were observed among female survivors of Hodgkin lymphoma treated with chest and neck radiotherapy, particularly during adolescence, and among hematopoietic stem cell transplant recipients exposed to total body irradiation or chronic graft-versus-host disease.

SMNs are predictable late effects requiring lifelong, exposure-anchored surveillance. Precision survivorship-integrating treatment exposures, transplant conditioning, and genetic predisposition-should guide future screening strategies.