Yazid Belkacemi1, Myriam Labopin2, Sebastian Giebel3, Gokoulakrichenane Loganadane4, Leszek Miszczyk5, Mauricette Michallet6, Gérard Socié7, Nicolaas P M Schaap8, Jan J Cornelissen9, Ibrahim Yakoub-Agha10, Emmanuelle Polge2, Mohamad Mohty2, Norbert Claude Gorin2, Arnon Nagler11. 1. Department of Radiation Oncology, Hôpitaux Universitaires Henri Mondor, INSERM U955 University of Paris-Est Créteil, Paris, France; Association of Radiotherapy and Oncology of the Mediterranean Area, Paris, France. Electronic address: yazid.belkacemi@aphp.fr. 2. EBMT Paris Study Office, Department of Hematology and Cell Therapy, INSERM U938, Hopital Saint Antoine and University UPMC, Paris, France. 3. Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Poland. 4. Department of Radiation Oncology, Hôpitaux Universitaires Henri Mondor, INSERM U955 University of Paris-Est Créteil, Paris, France. 5. Department of Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Poland. 6. Centre Hospitalier Lyon Sud, Service Hématologie, Lyon, France. 7. Department of Hematology-BMT, Hôpital Saint Louis, Paris, France. 8. Department of Hematology, Radboud University Medical Centre, Nijmegen, The Netherlands. 9. Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands. 10. CHU de Lille, INSERM U995, Université de Lille II, Lille, France. 11. EBMT Paris Study Office, Department of Hematology and Cell Therapy, INSERM U938, Hopital Saint Antoine and University UPMC, Paris, France; Hematology Division BMT and Cord Blood Bank, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Abstract
PURPOSE: Total-body irradiation (TBI) is a major constituent of myeloablative conditioning regimens. The standard technique consists of 12 Gy in 6 fractions over a period of 3 days. The Standard-fractionation compAred to one-daily fRaction total body irrAdiation prior to tranSplant In LEUkemia patieNts (SARASIN) study aimed to compare standard fractionation with once-daily fractionation before transplant in leukemia. METHODS AND MATERIALS: We retrospectively compared TBI regimens delivered in 2993 patients from the European Society for Blood and Marrow Transplantation database, who underwent transplantation between 2000 and 2014 for acute lymphoblastic leukemia (ALL, n = 1729) or acute myeloid leukemia (AML, n = 1264). TBI was delivered as either 12 Gy in 6 fractions (group 1, considered the reference group; 1362 ALL and 857 AML patients), 9 to 12 Gy in 2 fractions (group 2, 173 ALL and 256 AML patients), or 12 Gy in 3 to 4 fractions (group 3, 194 ALL and 151 AML patients). RESULTS: The median follow-up was 60 and 84 months in ALL and AML patients, respectively. At 5 years, the leukemia-free survival rate, overall survival rate, relapse incidence, and nonrelapse mortality rate were 46.6%, 50.4%, 28.8%, and 24.6%, respectively, in ALL patients and 46.6%, 48.9%, 29.7%, and 23.6%, respectively, in AML patients. In multivariate analyses, the outcomes of groups 2 and 3 were not statistically different from those in group 1. The cumulative incidence of secondary malignancies (SMs) was significantly higher in group 2 (7.2%; P < 10-6 for group 2 vs group 1). However, group 2 was not associated with an increase in SMs when we considered non-T-cell-depleted transplant patients. CONCLUSIONS: We showed that the 12-Gy fractionated TBI dose delivered either in 2 fractions or in 1 fraction per day over a period of 3 to 4 days resulted in nonsignificant differences in disease control and survival. However, 1-day fractionation may be associated with a higher risk of mucositis and hemorrhagic cystitis. The absence of a significant difference in the SM incidence in the non-T-cell-depleted group should be interpreted with caution in the context of a retrospective study design. Our findings are important to consider for radiation therapy department organization. In-depth analyses of other nonlethal toxicities and late effects are required.
PURPOSE: Total-body irradiation (TBI) is a major constituent of myeloablative conditioning regimens. The standard technique consists of 12 Gy in 6 fractions over a period of 3 days. The Standard-fractionation compAred to one-daily fRaction total body irrAdiation prior to tranSplant In LEUkemiapatieNts (SARASIN) study aimed to compare standard fractionation with once-daily fractionation before transplant in leukemia. METHODS AND MATERIALS: We retrospectively compared TBI regimens delivered in 2993 patients from the European Society for Blood and Marrow Transplantation database, who underwent transplantation between 2000 and 2014 for acute lymphoblastic leukemia (ALL, n = 1729) or acute myeloid leukemia (AML, n = 1264). TBI was delivered as either 12 Gy in 6 fractions (group 1, considered the reference group; 1362 ALL and 857 AMLpatients), 9 to 12 Gy in 2 fractions (group 2, 173 ALL and 256 AMLpatients), or 12 Gy in 3 to 4 fractions (group 3, 194 ALL and 151 AMLpatients). RESULTS: The median follow-up was 60 and 84 months in ALL and AMLpatients, respectively. At 5 years, the leukemia-free survival rate, overall survival rate, relapse incidence, and nonrelapse mortality rate were 46.6%, 50.4%, 28.8%, and 24.6%, respectively, in ALL patients and 46.6%, 48.9%, 29.7%, and 23.6%, respectively, in AMLpatients. In multivariate analyses, the outcomes of groups 2 and 3 were not statistically different from those in group 1. The cumulative incidence of secondary malignancies (SMs) was significantly higher in group 2 (7.2%; P < 10-6 for group 2 vs group 1). However, group 2 was not associated with an increase in SMs when we considered non-T-cell-depleted transplant patients. CONCLUSIONS: We showed that the 12-Gy fractionated TBI dose delivered either in 2 fractions or in 1 fraction per day over a period of 3 to 4 days resulted in nonsignificant differences in disease control and survival. However, 1-day fractionation may be associated with a higher risk of mucositis and hemorrhagic cystitis. The absence of a significant difference in the SM incidence in the non-T-cell-depleted group should be interpreted with caution in the context of a retrospective study design. Our findings are important to consider for radiation therapy department organization. In-depth analyses of other nonlethal toxicities and late effects are required.
Authors: Bianca A W Hoeben; Jeffrey Y C Wong; Lotte S Fog; Christoph Losert; Andrea R Filippi; Søren M Bentzen; Adriana Balduzzi; Lena Specht Journal: Front Pediatr Date: 2021-12-03 Impact factor: 3.418