0
selected
-
1.
Decitabine-Intensified Modified Busulfan/Cyclophosphamide Conditioning Regimen Improves Survival in Acute Myeloid Leukemia Patients Undergoing Related Donor Hematopoietic Stem Cell Transplantation: A Propensity Score Matched Analysis
Li, Z., Shi, W., Lu, X., Lu, H., Cao, X., Tang, L., Yan, H., Zhong, Z., You, Y., Xia, L., et al
Frontiers in oncology. 2022;12:844937
Abstract
To identify the benefit of decitabine (Dec)-intensified myeloablative conditioning on the outcomes of patients with acute myeloid leukemia (AML) after related donor hematopoietic stem cell transplantation (HSCT), we performed a retrospective matched-pair study from a pool of 156 patients to evaluate Dec [20 mg/m(2)/day intravenously (i.v.) on days -11 to -7]-intensified modified busulfan/cyclophosphamide (mBuCy) conditioning regimen vs. mBuCy regimen in 92 AML patients, with 46 patients in each cohort. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was lower in the Dec group (15.2% ± 0.3% vs. 32.6% ± 0.5%, P = 0.033). Compared with mBuCy group (15.5% ± 0.3%), a significantly higher proportion of limited chronic GVHD (cGVHD) in Dec group (35% ± 0.6%) was observed (P = 0.025). Dec-intensified mBuCy conditioning was associated with better 2-year overall survival (OS) and GVHD-free relapse-free survival (GRFS) (81% ± 6.2% vs. 59.4% ± 7.5%, P = 0.03; 58.7% ± 8.1% vs. 40.9% ± 7.3%, P = 0.042; respectively). Our results also elucidated that the Dec group had better 2-year OS and lower 2-year cumulative incidence of relapse (CIR) in patients acquiring haploidentical HSCT than that of the mBuCy group (84.8% ± 7.1% vs. 58.2% ± 10.3%, P = 0.047; 17.9% ± 0.8% vs. 40.0% ± 1.0%, P = 0.036; respectively), which did not increase the treatment-related mortality and regimen-associated toxicities. Dec-intensified myeloablative regimen and high-risk stratification were the variables associated with OS, leukemia-free survival (LFS), and GRFS in multivariate analysis. In high-risk patients, no differences were found in CIR, OS, LFS, and GRFS between the two groups. These data indicated that Dec-intensified mBuCy conditioning regimen was associated with better survival than mBuCy regimen in AML patients, especially in patients undergoing haploidentical HSCT.
-
2.
Comparative analysis of Decitabine intensified BUCY2 and BUCY2 conditioning regimen for high-risk MDS patients undergoing allogeneic hematopoietic stem cell transplantation
Zhang, R., Lu, X., Tang, L. V., Wang, H. F., Yan, H., You, Y., Zhong, Z. D., Shi, W., Xia, L. H.
Bone marrow transplantation. 2022
Abstract
The optimal conditioning regimen for high-risk myelodysplastic syndrome (MDS) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. This study aimed to explore the anti-leukemic efficacy and toxicity of Decitabine (Dec, 20 mg/m(2)/day, day -11 to -7) intensified BUCY2 vs. traditional regimen in high-risk MDS population. We retrospectively evaluated 93 consecutive high-risk MDS patients undergoing allo-HSCT in our institution, comparing discrepancies in clinical characteristics and outcomes between cases using Dec-intensified BUCY2 (n = 52) and traditional BUCY2 regimen (n = 41). Three-year cumulative incidence of relapse after Dec-intensified BUCY2 conditioning was remarkably lower than that of patients using BUCY2 regimen (20.2% vs. 39.0%, p = 0.034). Overall survival and disease-free survival at 3 years for Dec-intensified BUCY2 group were 70.2% and 64.9%, respectively, which were significantly improved when compared with BUCY2 group (51.1% and 43.9%, p = 0.031 and p = 0.027). Furthermore, overall survival and disease-free survival for MDS cases receiving cytoreduction therapy were dramatically better than patients in non-cytoreduction group (p = 0.041, p = 0.047). In summary, the Dec-intensified conditioning regimen could be effective and feasible, providing prominent recurrence control with moderate toxicity for high-risk MDS patients. These patients might also benefit from pre-transplant cytoreductive therapeutic schedules. Larger randomized controlled trials are still needed to further confirm these conclusions.
-
3.
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.
-
4.
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.
-
5.
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
-
-
-
Free full text
-
Full text
-
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.
-
6.
IDA-intensified hematopoietic cell transplantation improves relapse and survival of high-risk acute leukemia patients with minimal residual disease
Zhang, R., Lu, X., Wang, H., You, Y., Zhong, Z., Zang, S., Zhang, C., Shi, W., Li, J., Wu, Q., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
The optimal conditioning regimen of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients with minimal residual disease (MRD) remains controversial. We studied the results in 98 high-risk acute leukemia patients being transplanted with idarubicin (IDA)-intensified conditioning regimens between 2012 January and 2017 January. Among these patients, 31 (31.6%) had more than 5% marrow blasts at time of transplantation. 67 patients were in morphologic remission and MRD negative status at time of conditioning was achieved in 39 (39.8%) patients, whereas 28 (28.6%) remained carriers of any other positive MRD level in the bone marrow. Three-year relapse estimates of patients with MRD-positive remission was 22.0%, which was remarkably lower than patients with active disease (45.4%, p=0.027), but approximate to that of patients in MRD-negative remission (15.5%, p=0.522). There were no significant differences in terms of 3-year estimated overall survival (3y-OS) and disease-free survival (3y-DFS) between MRD-positive remission and MRD-negative remission groups (71.4% vs 79.1%, p=0.562; 67.9% vs 76.9%, p=0.634). Moreover, the estimated 3y-OS and 3y-DFS of patients in MRD-positive remission were significantly better than those in patients with active disease (71.4% vs 41.9%, p=0.033; 67.9% vs 38.7%, p=0.037). These data indicate that IDA-intensified conditioning allo-HSCT could overcome the negative prognostic impact of MRD.