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1.
Abnormalities Detected by Multicolor Flow Cytometry Detection of MRD in Allo-HSCT Recipients Originating from Donors: A Cohort Study
Wang, H., Wang, A., Chen, M., Gong, M., Wu, X., Zhen, J., Lu, Y.
Turkish journal of haematology : official journal of Turkish Society of Haematology. 2023
Abstract
BACKGROUND In minimal residual disease (MRD) analysis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), abnormal immunophenotyping are commonly considered as secondary recurrences or complications that lead to overtreatment. OBJECTIVE We aimed to confirm whether this phenotypic abnormality might be from the donor using multicolor flow cytometry (MFC). METHODS The MRD of the bone marrow (BM) specimens of 3395 patients who had received an allo-HSCT were analyzed using the conventional two-tubes eight-color MFC panel. The frequency of abnormal immunophenotypes were evaluated in three groups of non-malignance individuals. RESULTS The frequency of new abnormal polymorphism was 0.088% (3/3395) in patients that received an allo-HSCT. Abnormal cells in three patients in complete remission were Fcγ receptor IIIB (FcγRIIIB) gene deletion (CD16- neutrophils), CD2-CD159a-CD159c+ natural killer (NK) cells, and monoclonal B lymphocytosis (MBL). In addition, abnormal T cells (CD4+CD8+) were detected in one donor before allo-HSCT. Identical abnormalities were found in the peripheral blood of the corresponding donors of the three patients via MFC. In the non-malignant population, the incidence of FcγRIIIB deletion was 0.2% (11/5256), NK cells with the absence of CD2 and single positive CD159c was 0.05% (1/2000), and monoclonal CD4/CD8 double-positive T cells was 0.05% (1/2000), and the incidence of MBL was 1.3% (14/1100). The frequency of NK cells with the absence of CD2 was 1.3% (1/79) and with CD8dim was 14% (11/79) in NK cell lymphoma. These abnormalities could be identified by the two-tubes eight-ten color MFC panel: cκ/cλ/CD19/ CD5/CD20/CD38/CD45/CD56 (adding CD10 and CD34 as the ninth and tenth-color), CD16+CD56/CD5/CD3/ CD7/ CD4/ CD8/CD2/CD45 (adding CD117 as the ninth-color). CONCLUSION Abnormalities in recipients of an allo-HSCT detected by MRD may originate from the donors. Screening of donor specimens with a suitable two-tubes eight-ten color MFC panel may be a promising method to minimize misdiagnoses.
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2.
[Prognostic analysis and predictive model construction of bleeding events in allogeneic hematopoietic stem cell transplant patients]
Qi, J. Q., You, T., Wang, H., Han, W., Fan, Y., Chen, J., Wu, D. P., Han, Y.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2022;43(6):481-487
Abstract
Objective: To study hematopoietic stem cell transplantation-related bleeding prognosis and construct a bleeding prediction model. Methods: The clinical data of 555 patients with malignant hematologic diseases who underwent allogeneic hematopoietic stem cell transplantation between May 1(st) 2004, and April 1(st) 2012 was analyzed retrospectively, and a prediction model was constructed. Results: Of the 555 patients, a total of 302 (54.0% ) patients exhibited bleeding events of varying degrees, including 151 (27.0% ) with grade Ⅰ bleeding, 63 (11.0% ) with grade Ⅱ bleeding, 48 (9.0% ) with grade Ⅲ bleeding, and 40 (7.0% ) with grade Ⅳ bleeding. Multifactorial analysis showed that the overall mortality (HR=12.53, 95% CI 7.91-19.87, P<0.001) and non-recurrence mortality (HR=23.79, 95% CI 12.23-46.26, P<0.001) were higher in patients with higher bleeding grades (Ⅲ and Ⅳ bleeding) compared to those with lower bleeding grades. Additionally, the donor's underlying disease, graft-versus-host disease (GVHD) score, poor platelet reconstitution, and ineffective platelet transfusion were independently associated with bleeding risk. The bleeding model constructed using the above variables showed good accuracy (C-Index=0.934) , and its efficacy was significantly higher than previous bleeding models. Conclusion: Hematopoietic stem cell transplant patients are at increased risk of death after a bleeding event. The cross-validated bleeding risk prediction model is valuable for early intervention.
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3.
Clinical value of plasma and peripheral blood mononuclear cells Epstein-Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation
Zhou, X., Lu, X., He, J., Xu, Z., Li, Q., Ye, P., Zhong, Z., Shi, W., Yan, H., You, Y., et al
Frontiers in Cellular and Infection Microbiology. 2022;12:980113
Abstract
The application of intracellular and extracellular Epstein-Barr virus (EBV) DNA in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been poorly characterized. We conducted a combined prospective-retrospective study of 300 patients who underwent allo-HSCT between 2016 to 2019 in our center and monitored for EBV DNA within the first year after HSCT. Combining the optimal cut-off value of EBV DNA load (7.3×10(4) copies/10(6) cells) in peripheral blood mononuclear cells (PBMCs) and qualitative detection in plasma (400 copies/mL) allowed for the better differentiation of EBV-related posttransplant lymphoproliferative disorders (EBV-PTLD), with increased sensitivity (100%) and specificity (86%), and provided the effective risk stratification of EBV DNA level according to their impact on transplant outcomes. By multivariate analysis, patients with intermediate-level of EBV DNA load (low EBV DNA load in PBMCs or high load in PBMCs but negative in plasma) was associated with superior overall survival (HR 1.92, 95% CI 1.03-3.57, p=0.039) and lower transplant-related mortality (HR 3.35, 95% CI 1.31-8.58, p=0.012) compared to those with high-level (high load in PBMCs and positive in plasma). Notably, high EBV-level group had poor reconstitution of CD4+ and CD8+T cells, and both low and high EBV-level groups showed abnormally increase in IL-10 level within one year. Additionally, patients with peak EBV DNA load in PBMCs during 3-12 months had a higher incidence of chronic graft versus host disease (GVHD) than those within 3 months post transplantation (17.4% vs 13.7%, p=0.029). Collectively, EBV DNA in PBMCs can synergistically predict the risk of EBV-PTLD and GVHD. The intermediate-level of EBV DNA presented in plasma and PBMCs might contribute to a better reconstitution of T cells associated with favorable prognosis of allo-HSCT.
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4.
Prognostic Value of Thrombocytopenia in Myelodysplastic Syndromes After Hematopoietic Stem Cell Transplantation
Wang, H., Qi, J., Li, X., Chu, T., Qiu, H., Fu, C., Tang, X., Ruan, C., Wu, D., Han, Y.
Frontiers in oncology. 2022;12:940320
Abstract
Prolonged isolated thrombocytopenia (PT) is a common complication affecting the outcome of stem cell transplantation. In this study, we undertook a real-world study of 303 myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) between December 2007 and June 2018. 28.4% of MDS patients suffered from PT after HSCT. Survival analysis indicated that PT was associated with worse overall survival (OS) in MDS patients. The 2-year and 5-year OS in MDS patients with PT after HSCT were 49% and 47%, significantly worse than that of 68% and 60% in patients without PT (P=0.005). For RFS, patients with PT did not have an increased risk of disease relapse (P=0.964). After multivariate adjustment, PT was proved to be the independent risk factor associated with the worse OS (HR 1.49, 95% CI 1.00-2.21, P =0.048). We further analyzed risk factors associated with the occurrence of PT in MDS patients. Multiple logistic regression identified grade II-IV aGVHD, extensive chronic GVHD, hemorrhagic cystitis, and CMV activation as significant risk factors for developing PT. Among these variables, the Odds Ratio (OR) of grade II-IV aGVHD was the highest (P =0.001, OR: 2.65, 95% CI: 1.51-4.64). These data indicated the prognostic value of PT in MDS after HSCT. The identification of risk factors for PT may help improve patient management and lead to the design of effective treatment strategies.
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5.
[Effect of Philadelphia Chromosome Karyotype and Allogeneic Hematopoietic Stem Cell Transplantation on Patients with Acute Lymphoblastic Leukemia]
Wang, Y., Xu, X. M., Zhang, M., Wang, H.
Zhongguo shi yan xue ye xue za zhi. 2022;30(5):1397-1406
Abstract
AbstractObjective: To explore the effect of Philadelphia chromosome karyotype (Ph) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the treatment of acute lymphoblastic leukemia (ALL). METHODS The data of 429 patients with all from January 2012 to December 2020 were retrospectively analyzed. According to the results of cytogenetic karyotype analysis, they were divided into Ph(+) group (n=64), Ph(-) monomeric karyotype (MK) group (n=53) and Ph(-) NMK group (n=312). According to the treatment plan, they were divided into allo-HSCT group (n=236) and non-allo-HSCT group (n=193). The effects of karyotype and allo-HSCT on the short-term and long-term outcomes of all patients were analyzed. RESULTS Among the 429 patients, 6 (1.40%) died during induction therapy, 60 (13.99%) had no response, 363 (84.62%) achieved complete remission (CR) and 287 (66.90%) achieved minimal residual disease negative (MRD-). There was no significant difference in short-term efficacy (CR%, CR1%, MRD-%) among Ph(+) group, Ph(-) MK group and Ph(-) non-MK group (P>0.05). The median OS was 6.9 months (95% CI: 4.6-8.2 months) for 60 unresponsive patients and 39.8 months (95% CI: 28.6-45.9 months) for 363 CR patients. There was no significant difference in the long-term efficacy [5-year cumulative recurrence rate (CIR%), disease-free survival rate (DFS%) and overall survival rate (OS%) among Ph(-) group, Ph(-) MK group and Ph(-) non-MK group (P>0.05). Among 429 patients, 55.01% (236/429) underwent allo-HSCT. The short-term efficacy (CR%, MRD-%) and long-term efficacy (CIR%, DFS%, OS%)] of patients with allo-HSCT after more than 2 consolidation cycles were better than those of patients with non-allo-HSCT (P<0.05). For the three subgroups of Ph(+) group, Ph(-) MK group and Ph(-) non-MK group, the short-term and long-term efficacy of allo-HSCT patients was better than that of non-allo-HSCT patients. Multivariate logistic regression analysis showed that liver/spleen/lymph node enlargement was a risk factor for CIR, DFS and OS, with adjusted or of 1.23 (95% CI: 1.08-2.78, P=0.032), 1.21 (95% CI: 1.03-2.34, P=0.038) and 1.25 (95% CI: 1.08-2.97, P=0.028), respectively. No transplantation was a risk fator for CIR, DFS, OS. The adjusted or were 2.34 (95% CI: 1.18-5.39, P<0.001), 2.15 (95% CI: 1.10-4.34, P<0.001) and 2.28 (95% CI: 1.09-4.11, P<0.001), respectively. CONCLUSION Karyotype (Ph(+/-) and MK/non-MK) seems to have no effect on the short-term and long-term efficacy of all patients; allo-HSCT can affect the short-term and long-term efficacy of all patients and improve their prognosis; liver/spleen/lymph node enlargement and non-implementation of allo-HSCT treatment strategy are the risk factors for poor prognosis of all patients.
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6.
[The Prognostic Value of FOSB Gene in Acute Myeloid Leukemia]
Luan, S. H., Ma, Y. Q., Yang, J. J., Wang, H., Liu, D. H., Dou, L. P.
Zhongguo shi yan xue ye xue za zhi. 2022;30(4):1063-1070
Abstract
AbstractObjective: To analyze the expression of FOSB in acute myeloid leukemia (AML) and its correlation with prognosis of the patient based on the large sample data. METHODS The genome, transcriptome, gene chip and clinical information from multiple public databases were statistical analyzed. RESULTS The expression of FOSB gene in AML patients was significantly higher than that in normal people. The prognostic analysis of the 163 patients showed that the patients with high FOSB expression showed longer OS and EFS than those with FOSB low expression. The patients were further divided into chemotherapy group and allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the treatment method, and then each group was divided into two subgroups (FOSBhigh, FOSBlow) according to the median expression level of FOSB. In the allo-HSCT group, the patients with FOSB high expression was longer event-free survival (EFS: P=0.017) and overall survival (OS: P=0029). At the same time, allo-HSCT in patients with high FOSB expression could improve the prognosis of the patients (Chemotherapy vs Allo-HSCT, OS: P<0.001, EFS: P=0.007). Multivariate analysis showed that the high expression of FOSB was an independent favorable prognostic factor for EFS and OS (EFS: HR=0.501, P=0.019; OS: HR=0.461, P=0.009) of the patients. CONCLUSION The high expression of FOSB indicated a good prognosis for acute myeloid leukemia.
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7.
Influence of graft composition in patients with hematological malignancies undergoing ATG-based haploidentical stem cell transplantation
Zhang, R., Lu, X., Tang, L. V., Wang, H., Yan, H., You, Y., Zhong, Z., Shi, W., Xia, L.
Frontiers in immunology. 2022;13:993419
Abstract
To determine the influence of graft composition in haplo-HSCT, we summarized the long-term consequences of 251 consecutive transplantations from haploidentical donors. For donor-recipient HLA3/6-matched setting, 125 cases used G-CSF-mobilized BM and PBSCs mixtures, while 126 cases only used G-CSF-mobilized PBSCs in HLA4/6-matched transplantation. On the one hand, we wanted to explore the effect of harvests (CD34+ cells and TNCs dosages) on transplantation outcome in the context of haplo-HSCT no matter HLA4/6 or HLA3/6-matched setting. On the other hand, for patients using G-CSF-mobilized BM and PBSCs combination in HLA3/6-matched setting, we attempted to analyze whether TNCs or CD34+ cells from G-CSF-mobilized BM or G-CSF-mobilized PBSCs play the most paramount role on transplantation prognosis. Collectively, patients with hematologic malignancies receiving G-CSF-primed BM and PBSCs harvests had comparable consequences with patients only receiving G-CSF-mobilized PBSCs. Moreover, when divided all patients averagely according to the total amount of transfused nucleated cells, 3-year TRM of the intermediate group (13.06-18.05×10(8)/kg) was only 4.9%, which was remarkably reduced when compared to lower and higher groups with corresponding values 18.3%, 19.6% (P=0.026). The 3-year probabilities of OS and DFS of this intermediate group were 72.6% and 66.5%, which were slightly improved than the lower and higher groups. Most importantly, these data suggest that the transfused nucleated cells from G-CSF-primed BM above than 5.20×10(8)/kg could achieve remarkably lower TRM in haplo-HSCT receiving G-CSF-mobilized BM and PBSCs harvests. These encouraging results suggested that we could improve the efficacy of haplo-HSCT by adjusting the component and relative ratio of transfused graft cells. Nevertheless, the above findings should be confirmed in a randomized prospective comparative research with adequate follow-up.
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8.
Acute graft-versus-host disease increase risk and accuracy in prediction model of transplantation-associated thrombotic microangiopathy in patients with myelodysplastic syndrome
Zhang, Z., Wang, H., Qi, J., Tang, Y., Cai, C., Zhou, M., Pan, T., Wu, D., Han, Y.
Annals of hematology. 2022
Abstract
Allogeneic hematopoietic stem cell transplantation is the only curative therapy for patients with myelodysplastic syndrome. Transplantation-associated thrombotic microangiopathy (TA-TMA) remains a cause of death after transplantation. This study assessed the risk factors of TA-TMA and established a prediction model for this complication. We launched a real-world study from 303 MDS patients after allo-HSCT from Dec 1, 2007, to Jun 1, 2018. Logistic regression was used to analyze risk factors and to establish a nomogram. The accuracy of the model was assessed by C-index and calibration curve. TA-TMA class was associated with an over twofold increase in the risk of death (HR 2.66, 95% CI 1.39-5.09, p = 0.003). Stage III or IV acute graft-versus-host disease (aGVHD) (OR: 6.17, 95% CI: 2.19-17.18, p < 0.001) and occurrence time of aGVHD were the risk factors for TA-TMA. Next, we put these two variants and the other three variants into the prediction model via multivariate Lasso regression. In order to quantify the contribution of each factor, a nomogram was generated and displayed (C index of 0.783). TA-TMA predicts worsened outcomes of overall survival. A cross-validated multivariate score including aGVHD occurrence showed excellent concordance and efficacy of predicting TA-TMA in HSCT patients.
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9.
HLA-DQB1 mismatch increase risk of severe bleeding independently in recipients of allogeneic stem cell transplant
Qi, J., Zhang, R., Cai, C., Wang, H., Zhou, M., Shen, W., Tang, Y., Pan, T., Wu, D., Han, Y.
Annals of hematology. 2021
Abstract
Severe bleeding is a major cause of death in acute leukemia (AL) patients with graft-versus-host disease (GVHD) after allogene hematopoietic stem-cell transplantation (allo-HSCT). However, the prognostic value and prediction of HSCT-associated severe bleeding in GVHD patients have not been reported in cohort studies. We did a retrospective analysis of 200 AL patients with GVHD after allo-HSCT from Feb 1, 2014, to Dec 1, 2015. Multivariate analysis showed that the severe bleeding class was associated with the risk of death (HR 2.26, 95% CI 1.31-3.92, p<0.001***). In order to predict severe bleeding and figure out the solution to bleeding events, we established a multiple logistic regression model. HLA-DQB1 unmatching, megakaryocyte reconsititution failure, and III or IV GVHD were the independent risk factors for severe bleeding. Among all the variations above, OR of HLA-DQB1 was the highest (OR: 16.02, 95% CI: 11.54-48.68). Adding HLA-DQB1 to other factors improved the reclassification for predicting severe bleeding (NRI=0.195, z=2.634, p=0.008**; IDI=0.289, z=3.249, p<0.001***). Lasso regression was used to select variants. A nomogram of the logistic model was generated and displayed. Calibration curve demonstrated excellent accuracy in estimating severe bleeding (C index of 0.935). HLA-DQB1 showed excellent efficacy of predicting severe bleeding in HSCT patients.
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10.
ELISPOT assay of interferon gamma secretion for evaluate human cytomegalovirus reactivation risk in allo-HSCT recipients
Liang, H., Xia, J., Zhang, R., Yang, B., Wu, J., Gui, G., Huang, Y., Chen, X., Yang, R., Wang, H., et al
Journal of medical virology. 2021
Abstract
Human cytomegalovirus (HCMV) is a common cause of significant morbidity and mortality in transplant recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We evaluated IFN-? secretion by HCMV NLV-specific CD8+T cells in HCMV-reactivated allo-HSCT recipients using an enzyme-linked immunospot (ELISPOT) assay at 3 months post-transplantation. Blood samples from 47 recipients were tested for HCMV DNAemia, HCMV pp65 antigenemia, and anti-HCMV immunoglobulins (IgG/IgM) during 3 months post-transplantation. Of the 47 transplant recipients, 26 were HLA-A*02-positive and 21 were HLA-A*02-negative. The results were essentially consistent between the 47 transplant recipients and the HLA-A*02-positive recipients. HCMV DNAemia was not linearly correlated with IFN-? spot-forming cells (SFCs) counts; IFN-? SFCs counts did not differ significantly between the HCMV DNAemia-positive and -negative groups, whereas the HCMV-DNA virus loads were inversely correlated with the IFN-? SFCs counts. HCMV pp65 antigenemia was not linearly correlated with IFN-? SFCs counts; IFN-? SFCs counts in the HCMV pp65 antigenemia-positive and -negative groups were similar. More IFN-? SFCs counts were detected in transplant recipients with high anti-HCMV IgG antibody titers than in those with low anti-HCMV IgG titers pre-transplantation in the 47 recipients. Anti-HCMV IgG antibody titers were positively linearly correlated with IFN-? SFCs counts in HLA-A*02-positive recipients. The HCMV infection indicators used to monitor HCMV reactivation had different values in transplant recipients. The use of the IFN- ? SFCs counts measured by ELISPOT to evaluate the risk of HCMV reactivation needs further study. This article is protected by copyright. All rights reserved.