TOXICITIES OF TOTAL-BODY IRRADIATION FOR PEDIATRIC BONE-MARROW TRANSPLANTATION

Purpose: To determine the acute and tate effects, including cognitive function, of total body irradiation (TBI) and chemotherapy for bone ma rrow transplant (BMT) in children with immunodeficiency or hematologic disorders. Methods and Materials: At UCSF, 15 children with immunodef iciency disorders and 58 children with leukemia received chemoradiothe rapy between July 1982 and November 1993 and were evaluated for toxici ty. Patients with severe combined immunodeficiency disorder (SCID) rec eived 7 Gy TBI while leukemia patients received 12 Gy TBI. Results: Ei ght immunodeficient patients (53%) are alive at 4 months to 11 years p osttransplant. Acute toxicity was limited and treatment well tolerated . Most patients developed mild nausea and vomiting, skin rash, or eryt hema. Transient fever/chills, oral mucositis, and alopecia were noted in approximately 50% of patients. Seventy-three percent of patients de monstrated acute liver dysfunction, but only four (27%) developed veno -occlusive disease. All children had decreased growth velocity but nor mal growth hormone levels. Other endocrinologic evaluations including adrenocorticotropic hormone (ACTH), cortisol, and thyroid hormones wer e normal. Only one evaluable girl had delayed puberty with late onset of secondary sexual characteristics. Neuropsychological testing demons trated an intelligence quotient (IQ) reduction between the baseline an d 1 year post-BMT, with some recovery at 3 years. Only one patient dev eloped a clinically significant cataract. Thirteen percent of patients had chronic interstitial lung disease. Four children developed exosto sis. Only 1 of the 15 children developed a second malignancy (acute my elogenous leukemia) at age 5, 51 months posttransplant for SCID. For p atients with leukemia, similar toxicities were observed, Twenty-nine p ercent disease-free survival was noted with a mean follow-up of 4.7 ye ars. Twenty-two percent had chronic interstitial lung disease and two patients were diagnosed with cataracts. Graft-vs.-host-disease (GVHD), pubertal developmental arrest, and delayed puberty were seen. One chi ld developed papillary thyroid carcinoma, 49 months post-BMT. Similar neuropsychological testing decrements were also observed, Conclusion: Our experience suggests that intensive chemoradiotherapy, even at a yo ung age, does not cause severe, acute, or late toxicities but does res ult in a small IQ decrement and the risk of second malignancy in child ren with long-term follow-up.