Secondary Malignancies After Hematopoietic Stem Cell Transplantation

Secondary malignancies (SM) are a well-recognized long-term complication after hematopoietic cell transplantation (HCT), increasingly contributing to morbidity and mortality as post-transplant survival improves. However, the incidence, spectrum, and outcomes of SM remain incompletely defined in the context of evolving transplant practices and a growing population of long-term survivors.

To evaluate the incidence, risk factors, and outcomes of SM in a contemporary cohort of autologous and allogeneic HCT recipients.

Observational, retrospective, single-center study including all consecutive patients undergoing a first autologous or allogeneic HCT from any donor type at the Hospital Universitario y Politécnico La Fe (Valencia, Spain) between January 2007 and December 2024.

Among 2098 patients, 103 (4.9%) developed non-cutaneous SM, including 56 solid tumors (ST), 25 post-transplant lymphoproliferative disorders (PTLD), 15 therapy-related myelodysplastic syndromes/acute myeloid leukemia (t-MDS/AML), 2 donor cell leukemia, and 5 other hematologic malignancies. PTLD occurred earlier after allogeneic transplantation (median 3.9 months) than t-MDS/AML (median 47.0 months) and ST (median 51.5 months). Risk factors for ST included a history of prior malignancy (hazard ratio [HR] 2.96, 95% confidence interval [CI] 1.46 to 6.00; p = .003), allogeneic HCT (HR 2.44, 95% CI 1.29 to 4.60), and patient age ≥50 years (HR 1.89, 95% CI 1.07 to 3.35), whereas the risk of t-MDS/AML was higher among patients with a prior malignancy (HR 2.96, 95% CI 1.47 to 5.98). In the allogeneic setting, the use of post-transplant cyclophosphamide as graft-versus-host disease prophylaxis did not affect the risk of SM in multivariate analysis. SM ranked as the second and third leading causes of death after autologous and allogeneic HCT, respectively. Overall survival (OS) differed among SM subtypes entities, being particularly adverse for PTLD (1-year OS 19%, 95% CI 9 to 43) and better for solid tumors (5-year OS 43%, 95% CI 29 to 64).

SM are a significant determinant of post-transplant mortality, with risk shaped by prior malignancy, older age, and transplant type, and outcomes varying markedly according to subtype.