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Higher Reported Lung Dose Received during Total Body Irradiation for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia is Associated with Inferior Survival: A Report from the Children's Oncology Group
Esiashvili, N., Lu, X., Ulin, K., Laurie, F., Kessel, S., Kalapurakal, J. A., Merchant, T. E., Followill, D. S., Sathiaseelan, V., Schmitter, M. K., et al
International journal of radiation oncology, biology, physics. 2019
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Editor's Choice
Abstract
PURPOSE To examine the relationship between lung radiation dose and survival outcomes in children undergoing total body irradiation (TBI)-based hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL) on Children's Oncology Group (COG) trial. PATIENTS AND METHODS TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions) was used as part of 3 HSCT preparative regimens; allowing institutional flexibility regarding TBI techniques, including lung shielding. Lung doses as reported by each participating institution were calculated for different patient setups, with and without shielding, with a variety of dose calculation techniques. The association between lung dose and transplant-related mortality (TRM), relapse-free (RFS) and overall-survival (OS) was examined using Cox proportional hazard regression model controlling for the following variables: TBI dose rate, TBI fields, patient position during TBI, donor type, and pre-HSCT minimal residual disease (MRD) level. RESULTS From a total of 143 eligible patients127 had lung doses available for this analysis. The TBI techniques were heterogeneous. The mean lung dose was reported as 904.5cGy (SD +/-232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800cGy (p<0.001). Lung dose ≥800cGy influence on TRM was not significant (HR 1.78; p=0.21). On univariate analysis, lung dose ≥800cGy was associated with inferior RFS (HR 1.76; p=0.04) and OS (HR 1.85; p=0.03); in the multivariate analysis, OS maintained statistical significance (HR 1.85; p=0.04). CONCLUSION The variability in TBI techniques result in an uncertainty with reported lung doses. Lateral fields were associated with higher lung dose, hence better be avoided. Patients treated with lung dose <800 cGy in this study had better outcome. This approach is currently been investigated in COG AALL1331 study. Additionally, the Imaging and Radiation Oncology Core (IROC) Group is evaluating effects of TBI techniques on lung doses using a phantom.
PICO Summary
Population
Children with acute lymphoblastic leukaemia undergoing allogeneic stem cell transplantation (n=143)
Intervention
TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions), given with or without shielding, using heterogeneous TBI techniques.
Comparison
Lung doses as reported by each participating institution were calculated for different patient setups.
Outcome
The mean lung dose was reported as 904.5cGy. Patients treated with lateral fields were more likely to receive lung doses >/=800cGy. Lung dose >/=800cGy influence on TRM was not significant. On univariate analysis, lung dose >/=800cGy was associated with inferior RFS and OS; in the multivariate analysis, OS maintained statistical significance. The variability in TBI techniques resulted in an uncertainty with reported lung doses. Patients treated with lung dose <800 cGy had better outcome.
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Haploidentical versus matched donor stem cell transplantation for patients with hematological malignancies: a systemic review and meta-analysis
Yang, B., Yu, R., Cai, L., Bin, Guo, Chen, H., Zhang, H., He, P., Lu, X.
Bone marrow transplantation. 2018
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Editor's Choice
Abstract
We compared the safety and efficacy of haploidentical stem cell transplantation (haplo-SCT) to matched donor SCT (matched-SCT) in treating hematological malignancies. The Medline, Cochrane, EMBASE, and Google Scholar databases were searched through 21 June 2017 using the search term "(hematological disease) AND matched AND (haploidentical OR haplo-identical OR haplo identical OR haplo transplantation OR haplo transplant OR haplo-SCT OR haplo-HSCT OR haplo-HCT)." Twenty-five studies enrolling 11,359 patients (haplo-SCT: 2677; matched-SCT: 8682) were included. The primary outcomes were acute and chronic graft-versus-host disease (GVHD), non-relapse mortality, and 1-year cumulative incidence of relapse. Haplo-SCT was associated with similar risks as matched-SCT for all primary endpoints. Subgroup analysis of patients who received a matched-SCT from a related donor revealed that patients who received haplo-SCT had a lower risk of acute GVHD. Among patients who received reduced-intensity conditioning (RIC), those who received haplo-SCT had a higher risk of acute grade II-IV GVHD and non-relapse mortality than did patients who received a matched-SCT from a related or unrelated donor. Haplo-SCT should continue to be considered as a safe and effective transplant option when a matched donor is unavailable, but it may not be suitable for patients who receive RIC.