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Occurrence and influencing factors of cyclosporine A on the kidney injury following allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis
Lu, R., Shi, Y., Yang, M., Yang, N., He, S., Xin, L., Qin, Y., Li, H., Zeng, L., Zou, K., et al
International immunopharmacology. 2023;122:110633
Abstract
OBJECTIVE Whether cyclosporine A (CsA) is a risk factor of kidney injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been determined. We aim to comprehensively review the correlation and influencing factors between CsA and kidney injury in patients following allo-HSCT. METHODS We searched PubMed, Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, VIP, Wanfang and CBM Database from inception to March 2022. Two researchers independently conducted literature screening, data extraction and quality assessment. Qualitative and quantitative methods were combined to analyze the data. RESULTS We included a total of 30 studies. Meta-analyses of total incidence of kidney injury related to CsA was 37.0% [95% CI (25.4%, 48.6%); n = 15]. The proportion of CsA-related acute kidney injury to total acute kidney injury following allo-HSCT was 59.7% [95% CI (49.1%, 70.3%); n = 9]. One study found that AKI had a significant association with CsA in multivariate analysis [RR = 6.173; 95% CI (4.032, 9.434)]. With respect to cyclosporine combination and nephrotoxicity, 6/9 studies demonstrated that the concomitant medications for CsA (especially aminoglycoside antibiotics and amphotericin B) had negative effect on kidney functions related to CsA in allo-HSCT patients. No consensus was reached for "dose of CsA", "duration of CsA use", "comorbidities" and "CsA levels" across studies. CONCLUSIONS CsA may be a risk factor for kidney injury in patients following allo-HSCT, especially the concomitant use of CsA and nephrotoxic medications.
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Effectiveness of in vivo T-cell-depleted regimen containing porcine anti-lymphocyte globulin or rabbit anti-thymocyte globulin in preventing acute graft-versus-host disease after haploidentical haematopoietic stem cell transplantation
Xu, Z., Zhou, X., Zhao, X., Lu, X., Wang, H.
British journal of haematology. 2023
Abstract
To compare the clinical efficacy of porcine anti-lymphocyte globulin (p-ALG) and rabbit anti-thymocyte globulin (r-ATG) in the treatment of haematological malignancies using haploidentical haematopoietic stem cell transplantation (haplo-HSCT), this study was conducted. The incidences of neutrophil and platelet engraftment, respectively, were 100%, 93.6% and 94.4%; 100%, 93.6% and 90.3% in p-ALG 75 mg/kg (n = 57), p-ALG 90 mg/kg (n = 49), and r-ATG 7.5 mg/kg (n = 72). The median time to neutrophil engraftment and platelet engraftment were 11, 12 and 12 days (p = 0.032); 13, 14 and 13 days (p = 0.013), respectively. The incidence of grades II-IV acute graft-versus-host disease and cumulative incidence of chronic graft-versus-host disease were 16.7% versus 12.5% versus 13.3% (p = 0.817) and 14.7% versus 12.1% versus 19.5% in p-ALG 75 mg/kg, p-ALG 90 mg/kg and r-ATG groups. Notably, the cytomegalovirus infection rate in the p-ALG 75 mg/kg group was significantly lower than the other two groups. The cumulative incidence of 2-year relapse and 2-year overall survival rates were similar (p = 0.901, p = 0.497). The lower dose of p-ALG (75 mg/kg) had a similar efficacy and safety profile compared with r-ATG (7.5 mg/kg) in the setting of haplo-HSCT. Therefore, p-ALG (75 mg/kg) may be an appropriate alternative to r-ATG in the conditioning regimen of haplo-HSCT.
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Comparisons Between modified PTCY and G-CSF/ATG Regimens for Haploidentical Transplantation in Patients with Aplastic Anemia
Li, Y., Lu, X., Wang, N., Zhang, X., Cao, Y., Xiao, Y., Meng, F., Zhang, D., You, Y., Zou, L., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Haploidentical transplantation has become an alternative treatment option for aplastic anemia patients without matched sibling donors or matched unrelated donors. Recently, the post-transplantation cyclophosphamide (PTCY) regimen and granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG) regimen have become the most common protocols used worldwide. OBJECTIVE We designed this retrospective study to compare the outcomes of patients receiving a modified post-transplantation cyclophosphamide (mPTCY) regimen versus the G-CSF/ATG regimen. STUDY DESIGN We retrospectively reviewed and analyzed the clinical data of 130 aplastic anemia patients who underwent haplo-HSCT and received the mPTCY regimen (n=55) or G-CSF/ATG regimen (n=75) between Jan 2013 and Jun 2021 across seven transplant centers. RESULTS Neutrophil engraftment was successful in all patients within 30 days in the G-CSF/ATG group. The cumulative neutrophil engraftment rate in the mPTCY group was 96.36% (95% CI, 94.57-97.57, P=0.010). The median time of neutrophil engraftment in the G-CSF/ATG group was 10 (7-28) days, which was more rapid than that observed in the mPTCY group (P <0.001). There were no significant differences in the incidence of graft versus host disease (GVHD) between the two groups. The cumulative incidence of II-IV acute GVHD was 18.40% (95% CI, 4.27-40.31) in the mPTCY group and 19.32% (95% CI, 5.86-38.58) in the G-CSF/ATG group, while the cumulative incidence of III-IV acute GVHD was 7.31% (95% CI, 0.09-37.48) in the mPTCY group and 7.57% (95% CI, 0.20-34.19) in the G-CSF/ATG group. Similarly, no significant difference was observed between the two groups in terms of overall survival (OS), failure-free survival (FFS), and GVHD relapse-free survival (GRFS). The 2-year OS, FFS and GRFS rates were 95.91% (95% CI, 84.59-98.96), 92.25% (95% CI, 80.59-97.03) and 86.68% (95% CI, 73.98-93.44), respectively, in the mPTCY group and 86.67% (95% CI, 76.64-92.59), 81.28% (95% CI, 70.45-88.46) and 77.20% (95% CI, 65.89-85.16), respectively, in the G-CSF/ATG group. The transplantation-related mortality (TRM) rate was significantly higher in the G-CSG/ATG group than in the mPTCY group (13.33% in the G-CSG/ATG group versus 1.96% in the mPTCY group, P=0.022). In multivariate analysis, female donors, a higher hematopoietic cell transplantation comorbidity index (HCT-CI) and III-IV aGVHD were associated with worse survival outcomes. CONCLUSIONS In conclusion, the mPTCY and G-CSF/ATG regimens led to similar outcomes in AA patients, but quicker engraftment was observed with the ATG/G-CSF regimen, and a lower incidence of TRM was observed with the mPTCY regimen.
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4.
[Optimization of ATG dose in haploid hematopoietic stem cell transplantation for hematologic malignancies]
Zhou, X., Lu, X., Tang, L., Yan, H., Chen, W. L., Shi, W., Zhong, Z. D., You, Y., Xia, L. H., Hu, Y., et al
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2020;41(7):557-563
Abstract
Objective: To compare the clinical efficacy of different doses of rabbit antithymocyte globulin (rATG) in haplo-HSCT in the treatment of hematologic malignancies. Methods: Malignant hematological patients treated at our hospital from March 2013 to December 2018 were retrospectively analyzed. These patients were divided into three groups as per three doses of ATG (6 mg/kg, 7.5 mg/kg, and 9 mg/kg) in the conditioning regimens. The transplant outcomes were compared in terms of the occurrence of acute graft versus host disease (GVHD) , infection, and survival. Results: ?Total 288 patients were enrolled in the study, including 182 men and 106 women, with a median age of 18 (6-62) years. Total 110 patients were diagnosed with acute lymphoblastic leukemia (ALL) , 128 with acute myelogenous leukemia (AML) , 8 with chronic myeloid leukemia (CML) , 28 with myelodysplastic syndrome (MDS) , and 14 with mixed cell leukemia (MAL) . There were 159 patients in the ATG-6 group, 72 in the ATG-7.5 group, and 57 in the ATG-9 group. The median follow-up time of post transplantation was 14 (0.2-74) months. ?The incidence of neutrophil engraftment (96.9% , 97.2% , and 96.5% , respectively) and platelet engraftment (92.5% , 87.5% , and 86% , respectively) did not significantly differ among the ATG-6, ATG-7.5, and ATG-9 groups (P=0.972, P=0.276) . The incidence of grades 2-4 acute GVHD was 14.5% , 11.1% , and 8.8% in the three groups, respectively (P=0.493) , chronic GVHD incidence in the three group was 8.8% , 14.3% and 12.0% , respectively (P=0.493) . The infection rates of CMV and EBV in the ATG-9 group (77.2% and 12.5% ) were significantly higher than those in the ATG-6 (43.3% and 3.5% ) , and ATG -7.5 group (44.4% and 1.5% ) (P<0.001 and P=0.033, respectively) . ?Among the three groups, there were no significant difference in the 3-year overall survival [68.5% (95% CI 60.3% -77.9% ) , 60.1% (95% CI 48.3% -74.8% ) , 64.7% (95% CI 51.9% -80.7% ) ], cumulative incidences of relapse [34.6% (95% CI 34.3% -35.1% ) , 38.0% (95% CI 37.3% -38.7% ) , 20.6% (95% CI 20.0% -21.3% ) ], disease-free survival [53.3% (95% CI 44.9% -63.4% ) , 51.9% (95% CI 41% -65.8% ) , 63.9% (95% CI 51.9% -78.7% ) ] and non-relapse mortality [24.2% (95% CI 23.8% -24.5% ) , 26.0% (95% CI 25.4% -26.6% ) , 23.6% (95% CI 26.3% -28.2% ) ] (P=0.648, P=0.165, and P=0.486 and P=0.955) . Conclusion: Low dose (6 mg/kg) of rATG may increase the risk of grade ?-? aGVHD, and a high dose (9 mg/kg) of ATG could significantly increase the risk of CMV and EBV infection. Median dose (7.5 mg/kg) of ATG is expected to reduce the incidence of moderate to severe aGVHD and viral infections without increasing the mortality.
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Idarubicin-intensified haploidentical HSCT with GvHD prophylaxis of ATG and basiliximab provides comparable results to sibling donors in high-risk acute leukemia
Zhang, R., Shi, W., Wang, H. F., You, Y., Zhong, Z. D., Li, W. M., Zhang, C., Lu, X., Wang, Y. D., Zheng, P., et al
Bone Marrow Transplantation. 2017;52(9):1253-1260
Abstract
We designed a novel haploidentical hematopoietic stem cell transplantation (haplo-HSCT) system using idarubicin (IDA) intensified conditioning regimens and combination of antithymocyte globulin and basiliximab for GvHD prophylaxis. The outcomes of 110 high-risk acute leukemia patients undergoing haplo-HSCT were compared with 69 contemporaneous high-risk patients receiving HLA-matched sibling transplantation using uniform IDA-intensified regimens. The relapse incidence of haplo-HSCT was 23.4%, and 3-year overall survival (OS) and disease-free survival (DFS) achieved 62.9%, 59.1%, respectively. The cumulative incidences of II-IV and III-IV aGvHD were 28.6 and 14.3%, while limited and extensive cGvHD were 19.4, 13.8%. All these results were equivalent to those of concurrent identical sibling transplantation. Three-year OS and DFS for patients in advance stage reached 48.5, 47.3%. Furthermore, the relapse, 3-year OS of positive minimal residual disease (MRD) patients did not differ from negative MRD patients (18.9% vs 11.5%, 63.6% vs 69.6%), indicating our intensified haplo-HSCT technique could circumvent the dismal prognosis of MRD. These data provide reinforcing evidence that our haplo-HSCT system could dramatically improve the survival of high-risk acute leukemia with low relapse and acceptable transplantation-related mortality, and might be a promising therapeutic option for high-risk patients.