1.
The safety and efficacy of a novel hypo-fractionated total marrow and lymphoid irradiation before allogeneic stem cell transplantation for lymphoma and acute leukemia
Shi, L., Lu, X., Deng, D., Yang, L., Zhao, H., Shen, J., Wang, X., Xie, C., Liu, A., Cao, Y., et al
Clinical and translational radiation oncology. 2021;26:42-46
Abstract
PURPOSE Total body irradiation (TBI) has been widely utilized as part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), but is associated with significant toxicities. Targeted TBI using helical Tomotherapy allows precise and homogeneous tumor coverage and excellent sparing of organs at risk. The purpose of this study was to evaluate the clinical outcomes of a novel hypo-fractionation strategy for patients receiving total marrow and involved lymphoid irradiation (TMLI) as part of the conditioning regimen before HSCT. METHODS AND MATERIALS 61 patients (7 acute myelogenous leukemia (AML), 33 acute lymphoblastic leukemia (ALL), 18 non-Hodgkin's lymphoma (NHL), 3 mixed acute leukemia (MAL)) received conditioning radiation treatment with TMLI (8 Gy to bone marrow, 10 Gy to involved field in 2 fractions per day) in conjunction with chemotherapy before transplantation. RESULTS The median age of 61 patients with TMLI was 24 (4-54) years. The prescribed dose covered the entire bone and involved target volume, and the dose of organs at risk (OAR) was reduced by 28%-78% of the prescription dose. Grade 1-2 nausea and vomiting occurred in 12 patients and grade 1-2 pain in 6 patients during radiotherapy. Fatigue occurred in 16 patients. 2 patients had diarrhea, enteritis, and 1 patient had fever. None of patient had grade 3-4 non-hematologic adverse reactions. Late (30 days after HSCT) grade 2 toxicities including reversible enteritis occurred in 3 patients. 5 patients developed infectious pneumonia. The 2 years progression-free survival (PFS) was 64.1% (95% CI: 0.16-0.22) and overall survival (OS) was 74.7% (95% CI: 0.19-0.24) for the 61 patients who had received their planned HSCT. The 2-year non-relapse mortality was significantly reduced to 5% in this patient cohort. CONCLUSIONS This study demonstrates that hypo-fractionated TMLI (8 Gy to bone marrow, 10 Gy to involved field in a single day) as a conditioning regimen for lymphoma and acute leukemia was feasible and the clinical outcomes were acceptable.
2.
Comparing the outcomes between TMLI and non-TMLI conditioning regimens for adult high-risk acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: a single-center experience
Zhao, X., Lu, X., Tang, L., Yan, H., Chen, W., Shi, W., Zhong, Z., You, Y., Xia, L., Hu, Y., et al
Leukemia & lymphoma. 2020;:1-9
Abstract
This study aimed to retrospectively evaluate the outcomes of adult patients with high-risk acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either total marrow and lymphoid irradiation (TMLI)-containing or non-TMLI conditioning regimen. Seventy adult patients with high-risk ALL who received allo-HSCT were enrolled in this study and divided into two groups based on the conditioning regimen type (TMLI group: n = 29 and non-TMLI group: n = 41). We noted significant statistical differences in the 1-year estimated cumulative incidence of relapse (25% vs. 46.5%, p = 0.018), the 1-year estimated overall survival (73.1% vs. 52.6%, p = 0.033) and disease-free survival (65.2% vs. 48.2%, p = 0.026) but found no considerable difference in transplant-related mortality (12% vs. 13.4%, p = 0.619) between patients in the TMLI and non-TMLI groups. The TMLI-containing regimen is safe and alternative for patients with high-risk ALL undergoing allo-HSCT.
3.
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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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.