LEUKEMIA FOLLOWING LOW-DOSE TOTAL-BODY IRRADIATION AND CHEMOTHERAPY FOR NON-HODGKINS-LYMPHOMA

Purpose: Low-dose total body irradiation (TBI) is used to treat non-Ho dgkin's lymphoma (NHL) and several other malignancies. Large volumes o f bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. Patients and Metho ds: A cohort of 61 2-year survivors of NHL treated with low-dose TBI w as monitored for second cancer occurrence, Data on primary and subsequ ent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. Results: Thirte en second primary cancers occurred, Four patients developed acute nonl ymphocytic leukemia (ANLL), which represents a relative risk (90) of 1 17(95% confidence interval [Cl], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (M DS). All five patients with secondory hematologic malignancies subsequ ently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight sol id tumors were observed (RR = 2.0; 95% Cl, 0.9 to 4.0). The 15-year cu mulative risks of all second cancers and secondary ANLL were 37% and 1 7%, respectively. Conclusions: Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated wit h low-dose TBI in combination with CMT including alkylating agents. Ba sed on these results, approximately eight to nine excess ANLLs might b e expected to occur among 100 NHL patients treated with low-dose TBI a nd salvage treatment and followed-up for 15 years.