Treatment Outcomes of Re-Transplantation Using Repeated Total-Body Irradiation for Hematologic Disorder

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Total-body irradiation (TBI) has been widely used in hematopoietic stem cell transplantation (HSCT) as a part of conditioning therapy. Repeated HSCT is thought to be a one of the effective treatments for relapse patients, whereas a treatment strategy including conditioning regimen for repeated HSCT is still controversial. Moreover, the safety and efficacy of repeated TBI are poorly documented. This study aimed to clarify the outcomes of repeated TBI. Patients who met the following criteria were retrospectively reviewed from our institutional TBI database; 1) diagnosed with a hematologic disorder, 2) underwent twice or more HSCT, and 3) treated with TBI containing a conditioning regimen twice or more. Adverse events (AEs) of TBI, non-relapse mortality, overall survival, disease-free survival, and acute graft-versus-host disease (aGVHD) were evaluated. AEs were evaluated based on Common Terminology Criteria for Adverse Events 5.0. Forty-one of 775 cases in 39 patients were selected from our TBI database between July 2005 and January 2019 and the following data were extracted: median age, 39 (range, 15-71) years; type of disease, acute myeloid leukemia/acute lymphoid leukemia/myelodysplastic syndromes/others, 19/11/6/5; median interval from previous TBI, 331 (range, 34-1557) days; median dose of previous TBI, 7 (range, 2-12) Gy; disease status at second or more HSCT, complete remission/non-remission/graft failure, 15/20/6; conditioning regimen, myeloablative/non-myeloablative, 3/38; second TBI/third TBI, 39/2; median dose of second or third TBI, 4 (range, 2-12) Gy; and stem cell source, related peripheral blood stem cell/unrelated bone marrow/umbilical cord blood, 10/19/12. Forty cases (98%) involved the use of lead blocks to protect the lungs, kidneys, and lens. All TBI cases involved TBI using antero-posterior directed fields and a moving couch. The median follow-up after last HSCT was 139 (range, 3-2771) days. Grade 3 acute AEs were observed in 11 cases (mucositis, n=8; febrile neutropenia, n=3) (27%). No other acute AEs of grade 3 or greater were encountered. Grade3 or greater chronic AEs were not recorded. Thirty-four cases (83%) were died during the follow-up period, and the 1-year relapse rate and non-relapse mortality rate were 40% and 42%, respectively. The 1-year overall survival rate and disease-free survival rate were 31% and 18%, respectively. The mortality rate at 100 days after HSCT was 44%. Grade III or greater aGVHD were observed in 8 cases (20%). Toxicities induced by repeated TBI were well tolerated, although the survival outcomes of repeated HSCT using TBI compared with historical data without TBI. These results stress the necessity of more intensive re-irradiation approaches, using high-precision radiotherapy technique.