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1.
A prognostic score system in adult T-cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation
Xiao, M., Zhou, J., Zhu, X., He, Y., Wang, F., Zhang, Y., Mo, X., Han, W., Wang, J., Wang, Y., et al
Bone marrow transplantation. 2024
Abstract
Adult T-cell acute lymphoblastic leukemia (T-ALL) is highly aggressive with poor prognoses, while hematopoietic stem cell transplantation (HSCT) is a curable option. However, no transplant-specific prognostic model for adult T-ALL is available. We identified 301 adult T-ALL patients who received HSCT at our hospital between 2010 and 2022. These patients were randomly assigned at a 7:3 ratio to a derivation group of 210 patients and a validation group of 91 patients. Next, we developed a prognostic risk score system for adult T-ALL with HSCT, which we named COMM, including 4 predictors (central nervous system involvement, Non-CR1 (CR2+ or NR) at HSCT, minimal residual disease (MRD) ≥ 0.01% after first induction therapy, and MRD ≥ 0.01% before HSCT). Patients were categorized into three risk groups, low-risk (0), intermediate-risk (1-4), and high-risk (5-12), and their 3-year overall survival (OS) were 87.5% (95%CI, 78-93%), 65.7% (95%CI, 53-76%) and 20% (95%CI, 10-20%; P < 0.001), respectively. The area under the subject operating characteristic curve for 2-, 3- or 5-year OS in the derivation cohort and in the validation cohort were all greater than 0.75. Based on internal validation, COMM score system proved to be a reliable prognostic model that could discriminate and calibrate well. We expect that the first prognostic model in adults T-ALL after HSCT can provide a reference of prognostic consultation for patients and families, and also contribute to future research to develop risk adapted interventions for high-risk populations.
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2.
The effect of haploidentical hematopoietic stem cell transplantation on comutations based on next-generation sequencing in adult acute myeloid leukemia patients with the FLT3-ITD mutation
Tang, F., Zhao, X., Ruan, G., Jiang, Q., Jiang, H., Xu, L., Wang, Y., Zhang, X., Liu, K., Huang, X.
Hematological oncology. 2023
Abstract
According to the 2022 European LeukemiaNet, all acute myeloid leukemia (AML) cases with FLT3-ITD mutations are now categorized as intermediate risk irrespective of the FLT3-ITD allelic ratio or concurrent presence of NPM1 mutation. However, whether other next-generation sequencing (NGS) comutation genes can add layers to FLT3-ITD and whether the poor outcomes of FLT3-ITD comutations can be overcome by haploidentical hematopoietic stem cell transplantation (haplo-HSCT) are unclear. This study aimed to investigate which comutations based on NGS at diagnosis affect the clinical prognosis of de novo AML patients with FLT3-ITD mutations and the effect of haplo-HSCT on comutations. We analyzed 95 de novo AML patients with FLT3-ITD mutations from January 2018 to August 2021 based on the NGS 99-gene platform. Forty-one other types of molecular mutations were detected. The most common cooccurring mutations were NPM1 (n = 43, 45.3%) and DNMT3A (n = 21, 22.1%). NPM1 mutation did not affect the clinical outcomes. Acute myeloid leukemia patients with FLT3-ITD and DNMT3A comutations had significantly worse 3-year Disease-free survival (DFS) (49.5% vs. 69.3%, P = 0.01) and Overall survival (OS) rates (61.1% vs. 69.8%, P = 0.54) than those without DNMT3A mutations, and survival was significantly more favorable after haplo-HSCT than that after chemotherapy (3-year DFS, 85.7% vs. 30.8%, P = 0.006; 3-year OS, 85.7% vs. 43.1%, p = 0.08). In multivariate analysis, DNMT3A mutation was a risk factor for DFS, while haplo-HSCT was a protective factor. In conclusion, DNMT3A mutation might be a poor prognostic factor in adult AML patients with FLT3-ITD mutations, and haplo-HSCT could overcome the poor prognosis of DNMT3A comutation.
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3.
The association of intestinal microbiota diversity and outcomes of allogeneic hematopoietic cell transplantation: a systematic review and meta-analysis
Wang, S., Yue, X., Zhou, H., Chen, X., Chen, H., Hu, L., Pan, W., Zhao, X., Xiao, H.
Annals of hematology. 2023
Abstract
Growing evidence suggests that highly intestinal microbiota diversity modulates host inflammation and promotes immune tolerance. Several studies have reported that patients undergoing allo-HSCT have experienced microbiota disruption that is characterized by expansion of potentially pathogenic bacteria and loss of microbiota diversity. Thus, the primary aim of this meta-analysis was to determine the association of intestinal microbiota diversity and outcomes after allo-HSCT, and the secondary aim was to analyze the associations of some specific microbiota abundances with the outcomes of allo-HSCT. Electronic databases of Pubmed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2023, and 17 studies were found eligible. The pooled estimate suggested that higher intestinal microbiota diversity was significantly associated with overall survival (OS) benefit (HR = 0.66, 95% CI: 0.55-0.78), as well as decreased risk of transplant-related mortality (HR = 0.56, 95% CI: 0.41-0.76), and lower incidence of grade II-IV aGVHD (HR = 0.41, 95% CI: 0.27-0.63). Furthermore, higher abundance of Clostridiales was associated with a superior OS (HR = 0.40, 95% CI: 0.18-0.87), while higher abundance of Enterococcus (HR = 2.03, 95% CI: 1.55-2.65), γ-proteobacteria (HR = 2.82, 95% CI: 1.53-5.20), and Candida (HR = 3.80, 95% CI: 1.32-10.94) was an adverse prognostic factor for OS. Overall, this meta-analysis highlights the protective role of higher intestinal microbiota diversity on outcomes after allo-HSCT during both pre-transplant and post-transplant periods. Some specific microbiota can be useful in the identification of patients at risk of mortality, offering new tools for individualized pre-emptive or therapeutic strategies to improve allo-HSCT outcomes.
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4.
Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell transplantation: PAH risk score
Chong, S., He, Y., Wu, Y., Zhao, P., Zhu, X., Wang, F., Zhang, Y., Mo, X., Han, W., Wang, J., et al
Frontiers of medicine. 2022
Abstract
Skin and soft tissue infections (SSTIs) refer to infections involving the skin, subcutaneous tissue, fascia, and muscle. In transplant populations with hematological malignancies, an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly. However, to date, the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation (HSCT) patients remain unclear. This study included 228 patients (3.67%) who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People's Hospital. The overall annual survival rate was 71.5%. We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure (PPGF), comorbidities of acute kidney injury (AKI), and hospital-acquired pneumonia (HAP) were independent risk factors for death in the study population. A PPGF-AKI-HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP. The areas under the curves of internal and external validation were 0.833 (95% CI 0.760-0.906) and 0.826 (95% CI 0.715-0.937), respectively. The calibration plot revealed the high consistency of the estimated risks, and decision curve analysis showed considerable net benefits for patients.
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5.
Elevated RAP1A expression correlates with the severity of acute GVHD after umbilical cord blood transplantation
Wang, S., Wang, D., Chang, Y., Geng, L., Qiang, P., Sun, G., Tang, B., Zhao, X., Zhou, Z., Liu, H.
Transplant immunology. 2022;:101546
Abstract
BACKGROUND Acute graft-versus-host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation. Ras-related protein 1A (RAP1A) has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in aGVHD remains unclear. OBJECTIVE To study the role of RAP1A in the pathogenesis of aGVHD. MATERIAL AND METHODS Study participants included six patients with grade 2-4 aGVHD, 13 patients with grade 1 aGVHD, 11 patients without aGVHD, and 12 healthy people. The expression level of RAP1A in whole cells was detected by western blot and qRT-PCR. The proportions of CD4(+)CD25(+)FoxP3(+) Treg cells (T regulatory cells) and the expression of RAP1A in Treg cells in peripheral blood mononuclear cells (PBMCs) were detected by flow cytometry and the levels of related cytokines in the serum was detected by cytometric bead array. RESULTS We found the level of RAP1A was higher in patients than in healthy individuals. A negative correlation was noted between RAP1A and the number of Treg cells. In addition, the level of IL-10 in patients with grade 2-4 aGVHD was significantly lower than that in healthy donors, however, the level of TNF-ɑ in patients with grade 2-4 aGVHD was higher. Furthermore, we found a negative correlation between levels of IL-10 and RAP1A, and a positive correlation between TNF-ɑ and RAP1A. CONCLUSION The expression of RAP1A in patients with aGVHD was significantly increased, and shows potential as a target for the prevention and treatment of aGVHD.
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6.
Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation
Yu, X. X., Shang, Q. N., Liu, X. F., He, M., Pei, X. Y., Mo, X. D., Lv, M., Han, T. T., Huo, M. R., Zhao, X., et al
JCI insight. 2022
Abstract
Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several investigators have reported that adaptive NKG2C+ NK cells persistently expand during CMV reactivation. In our study, two cohorts were enrolled to explored the relationships among the NKG2C genotype, NKG2C+ NK cell reconstitution, and CMV infection. Multivariate analysis showed that donor NKG2C gene deletion was an independent prognostic factor for CMV reactivation and refractory CMV reactivation. Furthermore, the quantitative, qualitative reconstitution and anti-CMV function of adaptive NKG2C+ NK cells after transplantation was significantly lower in patients grafted with NKG2Cwt/del donor cells than in those grafted with NKG2Cwt/wt donor cells. The quantitative reconstitution of NKG2C+ NK cells at day 30 after transplantation was significantly lower in patients with treatment-refractory CMV reactivation than in those in the no-CMV-reactivation and CMV-reactivation groups. In humanized CMV-infected mice, we found that compared with those from NKG2Cwt/del donors, adaptive NKG2C+ NK cells from NKG2Cwt/wt donors induced earlier and stronger expansion of NKG2C+ NK cells and earlier and stronger CMV clearance in vivo. In conclusion, donor NKG2C homozygosity contributes to CMV clearance by promoting the quantitative and qualitative reconstruction of adaptive NKG2C+ NK cells after haploidentical allo-HSCT.
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7.
Cytomegalovirus infection is associated with rapid NK differentiation and reduced incidence of relapse in HLA matched sibling donor transplant patients
Han, T., Xie, J., Zhao, X., Lv, M., Chang, Y., Xu, L., Wang, Y., Zhang, X., Liu, K., Huang, X. J., et al
Clinical and experimental immunology. 2022
Abstract
The effect of cytomegalovirus (CMV) infection on leukemia relapse and the potential mechanism remains controversial. In this retrospective study, we evaluated the association among CMV infection, NK reconstitution and clinical outcomes in consecutive patients with hematologic malignancy who underwent HLA matched sibling donor transplantation (MST). In total, 228 patients were enrolled in the study between January 2010 and December 2011. The cumulative incidence of CMV infection on day 100 post-HSCT was 13.6 ± 4.9%. The probabilities of OS and DFS were 45.4% vs. 71.7% (P = 0.004) and 43.9% vs. 64.2% (P = 0.050) in the patients with CMV infection and without CMV infection, respectively. The cumulative incidence of treatment-related mortality (TRM) and relapse at 5 years was 48.6 ± 9.6% vs. 11.5 ± 2.9% (P < 0.001) and 6.2 ± 4.3% vs. 29.2 ± 3.9% (P = 0.024) in the patients with CMV infection and without CMV infection, respectively. In the multivariate analysis, CMV infection was associated with higher TRM, lower OS, and lower DFS. In addition, we found that CMV infection may promote the recovery of the absolute number of NK cells and promote the differentiation of NK cells post-MST. In conclusion, CMV infection may promote the recovery and differentiation of NK cells and was correlated with a lower relapse rate post-MST.
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8.
Prognosis and risk factors for central nervous system relapse after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia
Chen, Q., Zhu, X. L., Zhao, X., Liu, X., Fu, H. X., Zhang, Y. Y., Chen, Y. H., Mo, X. D., Han, W., Chen, H., et al
Annals of hematology. 2021
Abstract
We performed a nested case-control study to investigate the incidence, treatment, and prognosis of central nervous system (CNS) relapse after allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and compared the outcomes of patients with CNS relapse following haploidentical donor (HID) HSCT versus identical sibling donor (ISD) HSCT. A total of 37 patients (HID-HSCT, 24; ISD-HSCT, 13) developed CNS relapse after transplantation between January 2009 and January 2019, with an incidence of 1.81%. The median time from transplantation to CNS relapse was 239 days. Pre-HSCT CNS involvement (HR 6.940, 95% CI 3.146-15.306, p .001) was an independent risk factor for CNS relapse after allo-HSCT for AML. The 3-year overall survival (OS) for patients with CNS relapse was 60.3?±?8.8%, which was significantly lower than that in the controls (81.5?±?4.5%, p =?.003). The incidence of CNS relapse was 1.64% for patients who received HID-HSCT and 2.55% for those who received ISD-HSCT (p =?.193). There was no significant difference in OS between the HID-HSCT and ISD-HSCT subgroups among the patients with CNS relapse. In conclusion, CNS relapse is a rare but serious complication after allo-HSCT for AML, and the incidence and outcomes of patients with CNS relapse are comparable following HID-HSCT and ISD-HSCT.
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9.
CD8(+)CD161(hi) T cells are associated with acute graft-versus-host disease after haploidentical hematopoietic stem cell transplantation
Hong, Y., Liu, L., Chang, Y., Wang, Y., Zhang, X., Xu, L., Huang, X., Zhao, X.
Bone marrow transplantation. 2020
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10.
Posterior reversible encephalopathy syndrome (PRES) after haploidentical haematopoietic stem cell transplantation: incidence, risk factors and outcomes
Chen, Q., Zhao, X., Fu, H. X., Chen, Y. H., Zhang, Y. Y., Wang, J. Z., Wang, Y., Wang, F. R., Mo, X. D., Han, W., et al
Bone marrow transplantation. 2020
Abstract
Posterior reversible encephalopathy syndrome (PRES) is a gradually recognised neurological complication of allogenic haematopoietic stem cell transplantation (allo-HSCT). However, there is a paucity of information on PRES after haploidentical HSCT (haplo-HSCT). We performed a retrospective nested case-control study in patients following haplo-HSCT for malignant and nonmalignant haematologic diseases between January 2009 and December 2018 in our centre. A total of 45 patients were diagnosed with PRES after transplant, accounting for an incidence of 1.17%. Grades II to IV acute graft-versus-host disease (aGVHD) (HR 2.370, 95% CI 1.277-4.397, p = 0.006) and hypertension (HR 14.466, 95% CI 7.107-29.443, p < 0.001) were identified as risk factors for developing PRES after haplo-HSCT. There was no difference in overall survival (OS), disease-free survival (DFS), the cumulative incidence of relapse or nonrelapse mortality (NRM) between patients with PRES and controls without PRES following haplo-HSCT in either adults or children. All but one patient with PRES showed nearly complete clinical and neurologic recovery. In conclusion, PRES is a rare condition with benign outcomes following haplo-HSCT. Further multicentre prospective studies are needed to confirm the results and help to establish the standard therapy for posttransplant PRES.