Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study

Abstract

We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft-versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups.

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

“…Similar findings were observed in an Australian cohort of 3273 adults who received allogeneic HCT during 1992–2007. 77 Risks for several types of skin cancer are also strikingly elevated after HCT, 78,79 as reported in the Danish study of 3302 HCT recipients during 1999–2014 that leveraged the comprehensive reporting of all cutaneous malignancies [including basal and squamous cell carcinomas (SCC)] to general population cancer registries. 77 …”

How I monitor long-term and late effects after blood or marrow transplantation

“…The cumulative therapeutic exposures injure normal tissues, leading to premature onset of chronic health conditions such as subsequent neoplasms (SNs), [1][2][3] congestive heart failure (CHF), [4][5][6] coronary artery disease, 7 and musculoskeletal abnormalities. 8,9 In fact, the 15-year cumulative incidence of severe or life-threatening chronic health conditions exceeds 40%, 10,11 resulting in premature mortality [12][13][14][15][16][17] ( Figure 1). Because BMT survivors carry an inordinately high burden of morbidity and because many long-term complications may not manifest for years or even decades after BMT, survivors are in need of ongoing, life-long monitoring.…”

Risk of melanocytic nevi and nonmelanoma skin cancer in children after allogeneic hematopoietic stem cell transplantation

“…Studies in large cohorts of HSCT survivors show an increased risk of melanoma and nonmelanoma skin cancer (NMSC) compared with the general population. [1][2][3][4][5][6][7][8] Risk factors for subsequent skin cancers identified in these studies include young age (o 10 years) at HSCT and exposure to TBI, suggesting that pediatric HSCT survivors may be at particular risk for secondary skin cancers. 1,3 However, these studies have been composed mostly of adult survivors, and the pediatric-specific data have been limited to case reports and case series.…”