Total Body Irradiation In Very Young Children

Purpose/Objective(s)To examine patient characteristics, feasibility, and late effects in very young children who received total body irradiation (TBI) in preparation for bone marrow transplantation (BMT).Materials/MethodsBetween 1990 and 2011, 113 children ≤6 years of age received TBI in our department. Median age was 4. Primary diagnoses included: ALL (n = 50), AML (n = 29), other leukemias and lymphomas (n = 8), Wiskott Aldrich syndrome (n = 4), Fanconi anemia (n = 4), aplastic anemia (n = 3), SCID (n = 2), and other (n = 13). TBI was used in conjunction with a variety of chemotherapy agents including: thiotepa/cyclophosphamide (n = 58), cyclophosphamide alone (n = 22), thiotepa/fludarabine (n = 10), etoposide/cyclophosphamide (n = 7), cyclophosphamide/fludarabine (n = 7), and other (n = 9). The most common TBI schedules were 15 Gy in 12 fractions (n = 59) and 13.75 Gy in 11 fractions (n = 23) given 3 times per day at least 4 hours apart. Twice daily TBI using 1.5-2.25 Gy fractions for total doses of 6-15 Gy was used in 26 patients. Five patients received single doses of 2-6 Gy. Half value layer lung blocks were used with compensatory chest wall electron boosts. This was the second BMT for 8 patients and the third for 1: none of these patients had received previous TBI. Anesthesia was required in 35% of children using a prone and supine technique rather than our standard upright technique. The age range for children requiring anesthesia was 0-4 years and they were treated twice rather than three times daily. Among 47 surviving patients, late effects were examined in 39 with detailed long-term follow-up data.ResultsTBI was well tolerated both with and without anesthesia with only mild acute toxicity. Overall five-year survival was 49%. With median follow-up of 8 (1.3-18) years for surviving patients, endocrine dysfunction was the most common late effect (72%). Dyslipidemias (n = 8) were more common than obesity (n = 4) and insulin resistance (n = 2). Eleven patients suffered from neurocognitive delay. Eleven patients had cataracts while 8 patients had hearing loss. Musculoskeletal problems ranged from scoliosis (n = 3) to osteochondromas (n = 5) to limb hypoplasia (n = 1). Four second cancers were reported: osteosarcoma and thyroid cancer at 3 years, astrocytoma at 4 years, gliosarcoma at 5 years.ConclusionsTBI is an effective component of the pre-BMT cytoreduction regimen. It is feasible and well-tolerated even when anesthesia is required. TBI is especially appropriate for young children who have previously failed non-TBI BMTs or who cannot tolerate chemotherapy conditioning regimens. Survivors must be carefully followed for late-effects including second cancers. Purpose/Objective(s)To examine patient characteristics, feasibility, and late effects in very young children who received total body irradiation (TBI) in preparation for bone marrow transplantation (BMT). To examine patient characteristics, feasibility, and late effects in very young children who received total body irradiation (TBI) in preparation for bone marrow transplantation (BMT). Materials/MethodsBetween 1990 and 2011, 113 children ≤6 years of age received TBI in our department. Median age was 4. Primary diagnoses included: ALL (n = 50), AML (n = 29), other leukemias and lymphomas (n = 8), Wiskott Aldrich syndrome (n = 4), Fanconi anemia (n = 4), aplastic anemia (n = 3), SCID (n = 2), and other (n = 13). TBI was used in conjunction with a variety of chemotherapy agents including: thiotepa/cyclophosphamide (n = 58), cyclophosphamide alone (n = 22), thiotepa/fludarabine (n = 10), etoposide/cyclophosphamide (n = 7), cyclophosphamide/fludarabine (n = 7), and other (n = 9). The most common TBI schedules were 15 Gy in 12 fractions (n = 59) and 13.75 Gy in 11 fractions (n = 23) given 3 times per day at least 4 hours apart. Twice daily TBI using 1.5-2.25 Gy fractions for total doses of 6-15 Gy was used in 26 patients. Five patients received single doses of 2-6 Gy. Half value layer lung blocks were used with compensatory chest wall electron boosts. This was the second BMT for 8 patients and the third for 1: none of these patients had received previous TBI. Anesthesia was required in 35% of children using a prone and supine technique rather than our standard upright technique. The age range for children requiring anesthesia was 0-4 years and they were treated twice rather than three times daily. Among 47 surviving patients, late effects were examined in 39 with detailed long-term follow-up data. Between 1990 and 2011, 113 children ≤6 years of age received TBI in our department. Median age was 4. Primary diagnoses included: ALL (n = 50), AML (n = 29), other leukemias and lymphomas (n = 8), Wiskott Aldrich syndrome (n = 4), Fanconi anemia (n = 4), aplastic anemia (n = 3), SCID (n = 2), and other (n = 13). TBI was used in conjunction with a variety of chemotherapy agents including: thiotepa/cyclophosphamide (n = 58), cyclophosphamide alone (n = 22), thiotepa/fludarabine (n = 10), etoposide/cyclophosphamide (n = 7), cyclophosphamide/fludarabine (n = 7), and other (n = 9). The most common TBI schedules were 15 Gy in 12 fractions (n = 59) and 13.75 Gy in 11 fractions (n = 23) given 3 times per day at least 4 hours apart. Twice daily TBI using 1.5-2.25 Gy fractions for total doses of 6-15 Gy was used in 26 patients. Five patients received single doses of 2-6 Gy. Half value layer lung blocks were used with compensatory chest wall electron boosts. This was the second BMT for 8 patients and the third for 1: none of these patients had received previous TBI. Anesthesia was required in 35% of children using a prone and supine technique rather than our standard upright technique. The age range for children requiring anesthesia was 0-4 years and they were treated twice rather than three times daily. Among 47 surviving patients, late effects were examined in 39 with detailed long-term follow-up data. ResultsTBI was well tolerated both with and without anesthesia with only mild acute toxicity. Overall five-year survival was 49%. With median follow-up of 8 (1.3-18) years for surviving patients, endocrine dysfunction was the most common late effect (72%). Dyslipidemias (n = 8) were more common than obesity (n = 4) and insulin resistance (n = 2). Eleven patients suffered from neurocognitive delay. Eleven patients had cataracts while 8 patients had hearing loss. Musculoskeletal problems ranged from scoliosis (n = 3) to osteochondromas (n = 5) to limb hypoplasia (n = 1). Four second cancers were reported: osteosarcoma and thyroid cancer at 3 years, astrocytoma at 4 years, gliosarcoma at 5 years. TBI was well tolerated both with and without anesthesia with only mild acute toxicity. Overall five-year survival was 49%. With median follow-up of 8 (1.3-18) years for surviving patients, endocrine dysfunction was the most common late effect (72%). Dyslipidemias (n = 8) were more common than obesity (n = 4) and insulin resistance (n = 2). Eleven patients suffered from neurocognitive delay. Eleven patients had cataracts while 8 patients had hearing loss. Musculoskeletal problems ranged from scoliosis (n = 3) to osteochondromas (n = 5) to limb hypoplasia (n = 1). Four second cancers were reported: osteosarcoma and thyroid cancer at 3 years, astrocytoma at 4 years, gliosarcoma at 5 years. ConclusionsTBI is an effective component of the pre-BMT cytoreduction regimen. It is feasible and well-tolerated even when anesthesia is required. TBI is especially appropriate for young children who have previously failed non-TBI BMTs or who cannot tolerate chemotherapy conditioning regimens. Survivors must be carefully followed for late-effects including second cancers. TBI is an effective component of the pre-BMT cytoreduction regimen. It is feasible and well-tolerated even when anesthesia is required. TBI is especially appropriate for young children who have previously failed non-TBI BMTs or who cannot tolerate chemotherapy conditioning regimens. Survivors must be carefully followed for late-effects including second cancers.