title: National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report.
abstract: Subsequent neoplasms (SN) after hematopoietic cell transplantation (HCT) cause significant patient morbidity and mortality. Risks for specific SN types vary substantially, with particularly elevated risks for post-transplantation lymphoproliferative disorders, myelodysplastic syndrome/acute myeloid leukemia, and squamous cell malignancies. This document provides an overview of the current state of knowledge regarding SN after HCT and recommends priorities and approaches to overcome challenges and gaps in understanding. Numerous factors have been suggested to affect risk, including patient-related (eg, age), primary disease-related (eg, disease type, pre-HCT therapies), and HCT-related characteristics (eg, type and intensity of conditioning regimen, stem cell source, development of graft-versus-host disease). However, gaps in understanding remain for each of these risk factors, particularly for patients receiving HCT in the current era because of substantial advances in clinical transplantation practices. Additionally, the influence of nontransplantation-related risk factors (eg, germline genetic susceptibility, oncogenic viruses, lifestyle factors) is poorly understood. Clarification of the magnitude of SN risks and identification of etiologic factors will require large-scale, long-term, systematic follow-up of HCT survivors with detailed clinical data. Most investigations of the mechanisms of SN pathogenesis after HCT have focused on immune drivers. Expansion of our understanding in this area will require interdisciplinary laboratory collaborations utilizing measures of immune function and availability of archival tissue from SN diagnoses. Consensus-based recommendations for optimal preventive, screening, and therapeutic approaches have been developed for certain SN after HCT, whereas for other SN, general population guidelines are recommended. Further evidence is needed to specifically tailor preventive, screening, and therapeutic guidelines for SN after HCT, particularly for unique patient populations. Accomplishment of this broad research agenda will require increased investment in systematic data collection with engagement from patients, clinicians, and interdisciplinary scientists to reduce the burden of SN in the rapidly growing population of HCT survivors.
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: mortonli@mail.nih.gov.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.affiliation: Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.affiliation: Stem Cell Transplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.affiliation: Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Shahinaz M
authors.initials: SM
authors.lastname: Gadalla
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Steven
authors.initials: S
authors.lastname: Pavletic
authors.affiliation: National Marrow Donor Program/Be The Match and Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Burns
mesh_terms: D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D009316:National Institutes of Health (U.S.); D016609:Neoplasms, Second Primary / Q000209:etiology*; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D013997:Time Factors; D014481:United States
keywords: Hematopoietic cell transplantation; Late effects; Long-term follow-up; Second malignancies; Subsequent neoplasms