Читать книгу Blood and Marrow Transplantation Long Term Management - Группа авторов - Страница 143

After autologous HCT, secondary MDS/AML latently arises after DNA‐damaging chemotherapy or radiation exposures to the marrow microenvironment or in the reinfused autologous stem cells. The same may apply in allogeneic HCT if mixed donor chimerism persists and is especially concerning after HCT for WAS, DC, FA, or DBA.

Solid tumors may develop during LTFU and a study of >4900 survivors reported 22% CI of SMN at 30 years (8.1% if < age 20) [113]. This corresponds to a standardized incidence ratio (SIR) of 2.8‐fold higher than the rate for an age‐, sex‐, and calendar‐year matched SEER population; SIRs for children were 15‐fold higher at 1–10 years post‐HCT and 5‐fold higher at >30 years, thus lifetime monitoring is needed. It is noteworthy that the risk for SMN is not significantly different for 2–4.5 Gy TBI compared to chemotherapy only but still 2‐fold higher than the general population. Fractionated TBI 6–14 Gy is associated with higher rates of SMN, higher again for TBI 14.4–17.5 Gy, but not as high as for historical unfractionated TBI 6–10 Gy. The highest excess absolute risks per 1000 patient years were for breast cancer (EAR 2.2) and for oral (EAR 1.5) and skin cancers (EAR 1.5).

Certain heritable pediatric conditions have an increased risk for solid tumors independent of HCT that warrant SMN screening beyond the usual and might require relevant organ‐specific subspecialist consultation (see Table 8.1). Examples are DBA, certain phenotypes of FA, and DC. In patients with Li Fraumeni syndrome, HCT does not correct the underlying germline TP53 mutation and post‐HCT SMN risk is extremely high; cancer surveillance protocols are thus intense [114]; through age 18 years, surveillance focuses on “core” cancers: brain tumors, adrenocortical carcinoma, soft‐tissue sarcomas, bone tumors, and early onset breast cancer.

Multiple melanocytic nevi can develop after high‐dose chemotherapy exposures [115] and are best monitored periodically by a dermatologist with mole mapping. Osteochrondromas may appear incidentally on plain X‐rays after an average of 4.6 years in up to one‐quarter of children who received TBI before age 5 years; they rarely become malignant [116].