Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?
Patients who undergo autologous stem cell transplantation (ASCT) for lymphoma have a significant risk of therapy-related acute myeloid leukemia and myelodysplasia (t-AML/MDS). Compared to that seen in other indications such as breast cancer, multiple myeloma or germ cell tumors, there is a substantially increased risk for t-AML/MDS following ASCT for lymphoma. This risk has largely been attributed to the extent of pre-transplant chemotherapy and radiation therapy. In many of the larger series to date, it has not been possible to directly implicate autologous transplantation itself as a risk factor for t-AML/MDS. Although pre-transplant therapy is certainly an important factor in the development of t-AML/MDS, specific components of the autologous transplantation procedure itself may also contribute to the risk of t-AML/MDS. Specifically, priming chemotherapy, total body irradiation, and the extensive cellular proliferation which occurs during engraftment may all play a role in the development of t-AML/MDS. Furthermore, there is an increasing body of evidence that certain inherited polymorphisms in genes governing drug metabolism, DNA repair and leukemogenesis may influence susceptibility to t-AML/MDS. In this paper, we review the evidence implicating the above risk factors for t-AML/MDS, present a potential mechanism for t-AML/MDS and propose interventions to reduce the rate of t-AML/MDS in lymphoma patients.
Hake
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CR
Division of Neoplastic Diseases and Related Disorders, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Graubert
T A
TA
Fenske
T S
TS
D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000209:etiology*; D008223:Lymphoma / Q000601:surgery*; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000209:etiology; D014182:Transplantation, Autologous / Q000009:adverse effects*