Читать книгу Blood and Marrow Transplantation Long Term Management - Группа авторов - Страница 159

Little is known about the pathogenesis of solid tumors. An interaction of cytotoxic therapy, genetic predisposition, viral infection, and GvHD with the resulting antigenic stimulation and the use of immunosuppressive therapy, all appear to play a role in the development of new solid tumors [63,64].

Radiation‐related cancers generally have a long latency period, and the risk of such cancers is particularly high among patients undergoing irradiation at a young age. A large series reported an increased risk of brain and thyroid cancers after TBI given as part of myeloablative conditioning, though most of these patients had also received cranial irradiation prior to HSCT. Both thyroid cancer and brain tumors have been reported after exposure to radiation to the craniospinal axis and the neck when given as part of the conventional therapy for childhood acute lymphoblastic leukemia, HD and primary brain tumors. Similarly, osteogenic sarcoma and other connective tissue tumors have been recognized as secondary malignancies developing after radiation therapy in non‐transplanted patients. Those studies indicated a strong dose‐response relationship for radiation exposure, in addition to an increased risk with increasing exposure to alkylating chemotherapy agents. The increased risk of thyroid, breast, brain, bone and soft‐tissue malignancies seen after HSCT appear to be related, at least in part, to cumulative doses of radiation exposure, both as a result of the pretransplant treatment regimens, and the conditioning regimen used for transplantation.

Immunologic impairment may predispose patients to the development of squamous cell carcinoma of the oral cavity and skin, particularly in the context of cGVHD. These tumors have been observed particularly in patients with aplastic anemia conditioned with limited field irradiation or treated with Azathioprine for cGVHD [65]. In immune suppressed patients, oncogenic viruses, such as human papillomaviruses, may contribute to squamous cell cancers of the skin and buccal mucosa. The observed excess risk of squamous cell cancers of the buccal cavity and skin in males is unexplained but may be indicative of an interaction between ionizing radiation, immunodeficiency, and, conceivably factors such as smoking habits or alcohol consumption.

Patients with a family history of early‐onset (< age 40 years) cancers are at an increased risk for developing secondary cancers, and genetic predisposition is likely to have a substantial impact on the risk of secondary cancers. Studies exploring genetic predisposition and gene‐environment interactions have focused thus far on patients exposed to nontransplant conventional therapy for cancer. Future studies are needed in the transplant population to understand how genetic predisposition interacts with myeloablative chemotherapy, TBI and the attendant posttransplant immunosuppression, thereby leading to secondary solid tumors.