Abstract
Improving survival rates in children with malignancy have been achieved at the cost of a high frequency of late adverse effects of treatment, especially in intensively treated patients such as those undergoing haematopoietic stem cell transplantation (HSCT), many of whom suffer the high burden of chronic toxicity. Secondary malignant neoplasms (SMNs) are one of the most devastating late effects, cause much morbidity and are the most frequent cause of late (yet still premature) treatment-related mortality. They occur in up to 7% of HSCT recipients by 20 years post-HSCT, and with no evidence yet of a plateau in incidence with longer follow-up. This review describes the epidemiology, pathogenesis, clinical features and risk factors of the three main categories of post-HSCT SMNs. A wide range of solid SMNs has been described, usually occurring 10 years or more post-HSCT, related most often to previous or conditioning radiotherapy. Therapy-related acute myeloid leukaemia/myelodysplasia occurs earlier, typically three to seven years post-HSCT, mainly in recipients of autologous transplant and is related to previous alkylating agent or topoisomerase II inhibitor chemotherapy. Post-transplant lymphoproliferative disorders occur early (usually within two years) post-HSCT, usually presenting as Epstein-Barr virus-related B cell non-Hodgkin lymphoma.
Highlights
The increasing long-term survival rates of children with malignancy, reaching 75%–80% in resource-rich countries [1], mean that nearly one in 700 young adults is a survivor of a childhood malignancy [2]
A study of 3,182 survivors of allogeneic haematopoietic stem cell transplant (HSCT) for childhood acute leukaemia performed in 235 centres between 1964 and 1992 found a high and increasing cumulative incidence of Secondary malignant neoplasms (SMNs) reaching 11% at 15 years, with brain and thyroid tumours accounting for 56% of these [35]
Patient age at HSCT and latency expressed as median. 1 78% of patients had total body irradiation (TBI) or total lymphoid irradiation, which may have reduced power to detect their effect as risk factors
Summary
The increasing long-term survival rates of children with malignancy, reaching 75%–80% in resource-rich countries [1], mean that nearly one in 700 young adults is a survivor of a childhood malignancy [2]. An increasing number of patients from both of these groups become long-term survivors and are at very high risk of LAEs for a variety of reasons These reasons include preceding chemotherapy and/or radiotherapy, used either as conditioning for the transplant or during their earlier cytotoxic treatment, potentially toxic supportive care drugs, and the consequences of other serious complications after HSCT, especially infection and chronic graft-versus-host disease (GvHD). These constitute a powerful mix of additive and potentially synergistic chronic toxicities, leading to multiple and often severe late effects, most notably SMNs. In most cases, SMNs are regarded as occurring secondary to previous treatment, in some cases other genetic and environmental factors may play important roles in their pathogenesis. HSCT—Hematopoietic stem cell transplantation; GvHD—Graft versus host disease; t-therapy related; AML—acute myeloid leukaemia; MDS—Myelodysplasia; PBSC—Peripheral blood stem cell; PTLD—Post transplant lymphoproliferative disease; CNS—Central nervous system; EBV—Epstein-Barr virus; RIC—Reduced intensity conditioning
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