The Experts below are selected from a list of 3876 Experts worldwide ranked by ideXlab platform
Xiaojun Huang - One of the best experts on this subject based on the ideXlab platform.
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the european society for blood and marrow Transplantation ebmt consensus recommendations for donor selection in Haploidentical hematopoietic cell Transplantation
Bone Marrow Transplantation, 2020Co-Authors: Stefan O Ciurea, Franco Locatelli, Monzr Al M Malki, Piyanuch Kongtim, Xiaojun Huang, Ephraim J Fuchs, Leo Luznik, Fabio Ciceri, Franco Aversa, Luca CastagnaAbstract:The number of HLA-Haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for Transplantation, and choosing the best HLA-Haploidentical donor for Transplantation remains a challenge. Several approaches to Haploidentical Transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted Haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of Haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting Haploidentical donors for Transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms.
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Relationship of Cell Compositions in Allografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia: Effects of CD34+ and CD14+ Cell Doses
Wolters Kluwer, 2018Co-Authors: Le-qing Cao, Yu Wang, Xiaohui Zhang, Xiaojun Huang, Kaiyan Liu, Yan-rong Liu, Yingjun ChangAbstract:Background: The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell Transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated Haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA). Methods: A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann–Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results: A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after Transplantation, the cumulative incidence of II–IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124–4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after Transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14+ (P = 0.018) and CD34+ cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed. Conclusions: These results provide evidence and explain that higher doses of CD34+ and CD14+ cells in Haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA
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how do we choose the best donor for t cell replete hla Haploidentical Transplantation
Journal of Hematology & Oncology, 2016Co-Authors: Yingjun Chang, Xiaojun Huang, Ephraim J Fuchs, Leo LuznikAbstract:In Haploidentical stem cell Transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we focused on factors associated with transplant outcomes following unmanipulated haplo-SCT with anti-thymocyte globulin (ATG) or after T-cell-replete haplo-SCT with post-Transplantation cyclophosphamide (PT/Cy). We summarized the effects of the primary factors, including donor-specific antibodies against human leukocyte antigens (HLA); donor age and gender; killer immunoglobulin-like receptor-ligand mismatches; and non-inherited maternal antigen mismatches. We also offered some expert recommendations and proposed an algorithm for selecting donors for unmanipulated haplo-SCT with ATG and for T-cell-replete haplo-SCT with PT/Cy.
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recipient expression of ligands for donor inhibitory kirs enhances nk cell function to control leukemic relapse after Haploidentical Transplantation
European Journal of Immunology, 2015Co-Authors: Xiangyu Zhao, Yingjun Chang, Xiaohui Zhang, Xiaojun Huang, Kaiyan Liu, Xiaosu ZhaoAbstract:Natural killer (NK) cells that express self-HLA-specific receptors (where HLA is human leukocyte antigen) are "licensed" and more readily activated than unlicensed cells; therefore, NK-cell licensing could influence the antileukemia effects of NK cells following Haploidentical stem cell Transplantation (haplo-SCT). In this study, we compared the functionality of reconstituting NK cells, based on CD107α expression and interferon-γsecretion, in a cohort of 29 patients that expressed (n = 8) or lacked (n = 21) class I human leukocyte antigens for donor inhibitory killer cell immunoglobulin-like receptors (KIRs) following T-cell-replete haplo-SCT. We also addressed whether recipient expression of class I ligands for donor inhibitory KIRs could predict relapse occurrence in another cohort of 188 patients. A longitudinal analysis indicated that patients presenting class I for all donor inhibitory KIRs showed more capable functional NK effector cells when tested against class I negative K562 cells and primary leukemic cells within 3 months of Transplantation. The lowest 7-year relapse incidence was observed when donor KIRs were ligated by recipient class I (n = 60) compared with donor-host partnerships where donor KIR(+) cells were ligated by donor, but not recipient class I (n = 86, p = 0.026) or KIRs that were ligated by neither donor nor recipient class I (n = 42, p = 0.043). This study suggests that haplo-SCT recipients presenting class I for donor inhibitory KIRs promote NK-cell licensing, leading to decreased relapse rates.
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influence of two different doses of antithymocyte globulin in patients with standard risk disease following Haploidentical Transplantation a randomized trial
Bone Marrow Transplantation, 2014Co-Authors: Yangyuan Wang, Yingjun Chang, Xiaohui Zhang, Yuhong Chen, Feifei Tang, Daihong Liu, Fang Wang, Yuanwei Sun, K Y Liu, Xiaojun HuangAbstract:To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from Haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III–IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1–23.1%) than in the ATG-10 group (4.5%, CI, 0.7–8.3%, P=0.005, 95% CI for the difference, −19.4% to −3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1–33.5%) than in the ATG-6 group (9.6% (4.0–15.2%), P=0.001). The 1-year disease-free survival rates were 84.3% (77.3–91.3%) and 86.0% (79.2–92.8%) for the ATG-6 group and ATG-10 groups, respectively (P=0.88). In conclusion, although 6 mg/kg ATG applied in Haploidentical Transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.
Xiaohui Zhang - One of the best experts on this subject based on the ideXlab platform.
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myeloablative Haploidentical Transplantation is superior to chemotherapy for patients with intermediate risk acute myelogenous leukemia in first complete remission
Clinical Cancer Research, 2019Co-Authors: Yu Wang, Yingjun Chang, Xiaohui Zhang, Huan Chen, Fengrong Wang, Wei Han, Jingzhi Wang, Qian Jiang, Hao Jiang, Yao ChenAbstract:Purpose: Although myeloablative HLA Haploidentical hematopoietic stem cell Transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. Patients and Methods: In this prospective trial, among 443 consecutive patients ages 16–60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n = 69) or underwent haplo-HSCT (n = 78). Results: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; P = 0.0004 and 80.8% vs. 53.5%; P = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163–0.793; P = 0.011], OS (HR 0.361; 95% CI, 0.156–0.832; P = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057–0.459; P = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. Conclusions: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.
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Relationship of Cell Compositions in Allografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia: Effects of CD34+ and CD14+ Cell Doses
Wolters Kluwer, 2018Co-Authors: Le-qing Cao, Yu Wang, Xiaohui Zhang, Xiaojun Huang, Kaiyan Liu, Yan-rong Liu, Yingjun ChangAbstract:Background: The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell Transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated Haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA). Methods: A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann–Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results: A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after Transplantation, the cumulative incidence of II–IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124–4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after Transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14+ (P = 0.018) and CD34+ cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed. Conclusions: These results provide evidence and explain that higher doses of CD34+ and CD14+ cells in Haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA
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controlled randomized open label trial of risk stratified corticosteroid prevention of acute graft versus host disease after Haploidentical Transplantation
Journal of Clinical Oncology, 2016Co-Authors: Yingjun Chang, Yu Wang, Xiaohui Zhang, Huan Chen, Yuhong Chen, Fengrong Wang, Wei Han, Yuqian Sun, Chenhua Yan, Feifei TangAbstract:PurposeThis study evaluated whether a prophylaxis strategy directed by the graft-versus-host disease (GVHD) biomarker might reduce the 100-day incidence of acute GVHD grades II to IV.Patients and MethodsThis controlled, open-label, randomized trial included 228 patients who underwent Haploidentical Transplantation. On the basis of bone marrow allogeneic graft CD4:CD8 ratios, patients were categorized as low risk (n = 83; group A) or high risk (n = 145). Patients at high risk were randomly assigned to either receive (n = 72; group B) or not receive (n = 73; group C) low-dose corticosteroid prophylaxis.ResultsThe incidence in group B was 21% (95% CI, 11% to 31%) compared with 26% (95% CI, 16%to 36%; P = .43) in group A and 48% (95% CI, 32% to 60%; P < .001) in group C. Low-dose corticosteroid prophylaxis was significantly associated with a relatively low risk of acute GVHD grades II to IV (hazard ratio, 0.66; 95% CI, 0.49 to 0.89; P = .007) and rapid platelet recovery (hazard ratio, 0.30; 95% CI, 0.23 to 0....
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recipient expression of ligands for donor inhibitory kirs enhances nk cell function to control leukemic relapse after Haploidentical Transplantation
European Journal of Immunology, 2015Co-Authors: Xiangyu Zhao, Yingjun Chang, Xiaohui Zhang, Xiaojun Huang, Kaiyan Liu, Xiaosu ZhaoAbstract:Natural killer (NK) cells that express self-HLA-specific receptors (where HLA is human leukocyte antigen) are "licensed" and more readily activated than unlicensed cells; therefore, NK-cell licensing could influence the antileukemia effects of NK cells following Haploidentical stem cell Transplantation (haplo-SCT). In this study, we compared the functionality of reconstituting NK cells, based on CD107α expression and interferon-γsecretion, in a cohort of 29 patients that expressed (n = 8) or lacked (n = 21) class I human leukocyte antigens for donor inhibitory killer cell immunoglobulin-like receptors (KIRs) following T-cell-replete haplo-SCT. We also addressed whether recipient expression of class I ligands for donor inhibitory KIRs could predict relapse occurrence in another cohort of 188 patients. A longitudinal analysis indicated that patients presenting class I for all donor inhibitory KIRs showed more capable functional NK effector cells when tested against class I negative K562 cells and primary leukemic cells within 3 months of Transplantation. The lowest 7-year relapse incidence was observed when donor KIRs were ligated by recipient class I (n = 60) compared with donor-host partnerships where donor KIR(+) cells were ligated by donor, but not recipient class I (n = 86, p = 0.026) or KIRs that were ligated by neither donor nor recipient class I (n = 42, p = 0.043). This study suggests that haplo-SCT recipients presenting class I for donor inhibitory KIRs promote NK-cell licensing, leading to decreased relapse rates.
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influence of two different doses of antithymocyte globulin in patients with standard risk disease following Haploidentical Transplantation a randomized trial
Bone Marrow Transplantation, 2014Co-Authors: Yangyuan Wang, Yingjun Chang, Xiaohui Zhang, Yuhong Chen, Feifei Tang, Daihong Liu, Fang Wang, Yuanwei Sun, K Y Liu, Xiaojun HuangAbstract:To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from Haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III–IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1–23.1%) than in the ATG-10 group (4.5%, CI, 0.7–8.3%, P=0.005, 95% CI for the difference, −19.4% to −3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1–33.5%) than in the ATG-6 group (9.6% (4.0–15.2%), P=0.001). The 1-year disease-free survival rates were 84.3% (77.3–91.3%) and 86.0% (79.2–92.8%) for the ATG-6 group and ATG-10 groups, respectively (P=0.88). In conclusion, although 6 mg/kg ATG applied in Haploidentical Transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.
Antonio Pagliuca - One of the best experts on this subject based on the ideXlab platform.
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high fever occurring 4 to 5 days post transplant of Haploidentical bone marrow or peripheral blood stem cells after reduced intensity conditioning associated with the use of post transplant cyclophosphamide as prophylaxis for graft versus host disease
Biology of Blood and Marrow Transplantation, 2015Co-Authors: Antonio Pagliuca, Paul V OdonnellAbstract:Recently, twomulticenter reports in theMay and June issues of Biology of Blood and Marrow Transplantation showed that peripheral blood stem cells (PBSCs) can be used safely and effectively as the graft source for Transplantation from Haploidentical donors after reduced-intensity conditioning for treatment of high-risk hematologic malignancies [1,2]. Both reports used post-transplant cyclophosphamide (PTCy) to eliminate alloreactive T cells as previously described [3]. Our own publication [2] was a 4-center study of 55 patients with acute leukemiasor lymphomaswitha17-monthmedian follow-up.Of note, a preliminary report of our first 29 patients was reported in abstract form at the Tandem BMTMeetings of 2012 [4]. In the setting of Haploidentical Transplantation of PBSCs after an ablative conditioning regimen and use of PTCy as graft-versus-host disease (GVHD) prophylaxis, Solomon et al. [5] and Grosso et al. [6] reported that high fever was commonly observed at 4 to 5 days post-transplant. In the absenceof documented infection, itwashypothesized that the feverwas likely a cytokine-mediated phenomenon associated either with initial proliferation of alloreactive T cells or from the actual destruction of alloreactive T cells by PTCy given per protocol on days þ3 and þ4. Here, we report that a similar incidence of high fever at 4 to 5 days post-transplant also was observed in our recently reported study of Haploidentical PBSCs [2]. A similar finding of high fever post-transplant also was observed in patients who had undergone bone marrow Transplantation from Haploidentical donors [7]. The median Tmax of patients transplanted with PBSCs (39.7 C) was significantly higher than the Tmax of patients transplanted with bone marrow (38.6 C, P 1⁄4 .007), possibly reflecting the 5to 10-fold greater content of T cells in PBSC allografts from
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peripheral blood hematopoietic stem cells for Transplantation of hematological diseases from related Haploidentical donors after reduced intensity conditioning
Biology of Blood and Marrow Transplantation, 2014Co-Authors: Majid Kazmi, Matthew Streetly, Antonio Pagliuca, Kenneth F Bradstock, Victor Noriega, Victoria Potter, Donal Mclornan, Judith C W MarshAbstract:Abstract In a multicenter collaboration, we carried out T cell–replete, peripheral blood stem cell (PBSC) Transplantations from related, HLA-Haploidentical donors with reduced-intensity conditioning (RIC) and post-Transplantation cyclophosphamide (Cy) as graft-versus-host disease (GVHD) prophylaxis in 55 patients with high-risk hematologic disorders. Patients received 2 doses of Cy 50 mg/kg i.v. on days 3 and 4 after infusion of PBSC (mean, 6.4 × 10 6 /kg CD34 + cells; mean, 2.0 × 10 8 /kg CD3 + cells). The median times to neutrophil (500/μL) and platelet (>20,000/μL) recovery were 17 and 21 days respectively. All but 2 of the patients achieved full engraftment. The 1-year cumulative incidences of grade II and grade III acute GVHD were 53% and 8%, respectively. There were no cases of grade IV GVHD. The 2-year cumulative incidence of chronic GHVD was 18%. With a median follow-up of 509 days, overall survival and event-free survival at 2 years were 48% and 51%, respectively. The 2-year cumulative incidences of nonrelapse mortality and relapse were 23% and 28%, respectively. Our results suggest that PBSC can be substituted safely and effectively for bone marrow as the graft source for Haploidentical Transplantation after RIC.
Yingjun Chang - One of the best experts on this subject based on the ideXlab platform.
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myeloablative Haploidentical Transplantation is superior to chemotherapy for patients with intermediate risk acute myelogenous leukemia in first complete remission
Clinical Cancer Research, 2019Co-Authors: Yu Wang, Yingjun Chang, Xiaohui Zhang, Huan Chen, Fengrong Wang, Wei Han, Jingzhi Wang, Qian Jiang, Hao Jiang, Yao ChenAbstract:Purpose: Although myeloablative HLA Haploidentical hematopoietic stem cell Transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. Patients and Methods: In this prospective trial, among 443 consecutive patients ages 16–60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n = 69) or underwent haplo-HSCT (n = 78). Results: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; P = 0.0004 and 80.8% vs. 53.5%; P = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163–0.793; P = 0.011], OS (HR 0.361; 95% CI, 0.156–0.832; P = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057–0.459; P = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. Conclusions: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.
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Relationship of Cell Compositions in Allografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia: Effects of CD34+ and CD14+ Cell Doses
Wolters Kluwer, 2018Co-Authors: Le-qing Cao, Yu Wang, Xiaohui Zhang, Xiaojun Huang, Kaiyan Liu, Yan-rong Liu, Yingjun ChangAbstract:Background: The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell Transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated Haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA). Methods: A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann–Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results: A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after Transplantation, the cumulative incidence of II–IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124–4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after Transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14+ (P = 0.018) and CD34+ cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed. Conclusions: These results provide evidence and explain that higher doses of CD34+ and CD14+ cells in Haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA
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controlled randomized open label trial of risk stratified corticosteroid prevention of acute graft versus host disease after Haploidentical Transplantation
Journal of Clinical Oncology, 2016Co-Authors: Yingjun Chang, Yu Wang, Xiaohui Zhang, Huan Chen, Yuhong Chen, Fengrong Wang, Wei Han, Yuqian Sun, Chenhua Yan, Feifei TangAbstract:PurposeThis study evaluated whether a prophylaxis strategy directed by the graft-versus-host disease (GVHD) biomarker might reduce the 100-day incidence of acute GVHD grades II to IV.Patients and MethodsThis controlled, open-label, randomized trial included 228 patients who underwent Haploidentical Transplantation. On the basis of bone marrow allogeneic graft CD4:CD8 ratios, patients were categorized as low risk (n = 83; group A) or high risk (n = 145). Patients at high risk were randomly assigned to either receive (n = 72; group B) or not receive (n = 73; group C) low-dose corticosteroid prophylaxis.ResultsThe incidence in group B was 21% (95% CI, 11% to 31%) compared with 26% (95% CI, 16%to 36%; P = .43) in group A and 48% (95% CI, 32% to 60%; P < .001) in group C. Low-dose corticosteroid prophylaxis was significantly associated with a relatively low risk of acute GVHD grades II to IV (hazard ratio, 0.66; 95% CI, 0.49 to 0.89; P = .007) and rapid platelet recovery (hazard ratio, 0.30; 95% CI, 0.23 to 0....
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how do we choose the best donor for t cell replete hla Haploidentical Transplantation
Journal of Hematology & Oncology, 2016Co-Authors: Yingjun Chang, Xiaojun Huang, Ephraim J Fuchs, Leo LuznikAbstract:In Haploidentical stem cell Transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we focused on factors associated with transplant outcomes following unmanipulated haplo-SCT with anti-thymocyte globulin (ATG) or after T-cell-replete haplo-SCT with post-Transplantation cyclophosphamide (PT/Cy). We summarized the effects of the primary factors, including donor-specific antibodies against human leukocyte antigens (HLA); donor age and gender; killer immunoglobulin-like receptor-ligand mismatches; and non-inherited maternal antigen mismatches. We also offered some expert recommendations and proposed an algorithm for selecting donors for unmanipulated haplo-SCT with ATG and for T-cell-replete haplo-SCT with PT/Cy.
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recipient expression of ligands for donor inhibitory kirs enhances nk cell function to control leukemic relapse after Haploidentical Transplantation
European Journal of Immunology, 2015Co-Authors: Xiangyu Zhao, Yingjun Chang, Xiaohui Zhang, Xiaojun Huang, Kaiyan Liu, Xiaosu ZhaoAbstract:Natural killer (NK) cells that express self-HLA-specific receptors (where HLA is human leukocyte antigen) are "licensed" and more readily activated than unlicensed cells; therefore, NK-cell licensing could influence the antileukemia effects of NK cells following Haploidentical stem cell Transplantation (haplo-SCT). In this study, we compared the functionality of reconstituting NK cells, based on CD107α expression and interferon-γsecretion, in a cohort of 29 patients that expressed (n = 8) or lacked (n = 21) class I human leukocyte antigens for donor inhibitory killer cell immunoglobulin-like receptors (KIRs) following T-cell-replete haplo-SCT. We also addressed whether recipient expression of class I ligands for donor inhibitory KIRs could predict relapse occurrence in another cohort of 188 patients. A longitudinal analysis indicated that patients presenting class I for all donor inhibitory KIRs showed more capable functional NK effector cells when tested against class I negative K562 cells and primary leukemic cells within 3 months of Transplantation. The lowest 7-year relapse incidence was observed when donor KIRs were ligated by recipient class I (n = 60) compared with donor-host partnerships where donor KIR(+) cells were ligated by donor, but not recipient class I (n = 86, p = 0.026) or KIRs that were ligated by neither donor nor recipient class I (n = 42, p = 0.043). This study suggests that haplo-SCT recipients presenting class I for donor inhibitory KIRs promote NK-cell licensing, leading to decreased relapse rates.
Luca Castagna - One of the best experts on this subject based on the ideXlab platform.
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the european society for blood and marrow Transplantation ebmt consensus recommendations for donor selection in Haploidentical hematopoietic cell Transplantation
Bone Marrow Transplantation, 2020Co-Authors: Stefan O Ciurea, Franco Locatelli, Monzr Al M Malki, Piyanuch Kongtim, Xiaojun Huang, Ephraim J Fuchs, Leo Luznik, Fabio Ciceri, Franco Aversa, Luca CastagnaAbstract:The number of HLA-Haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for Transplantation, and choosing the best HLA-Haploidentical donor for Transplantation remains a challenge. Several approaches to Haploidentical Transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted Haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of Haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting Haploidentical donors for Transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms.
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post Transplantation cyclophosphamide based Haploidentical Transplantation as alternative to matched sibling or unrelated donor Transplantation for hodgkin lymphoma a registry study of the lymphoma working party of the european society for blood and marrow Transplantation
Journal of Clinical Oncology, 2017Co-Authors: Carmen Martinez, Luca Castagna, Jorge Gayoso, Carmen Canals, Herve Finel, Karl S Peggs, Alida Dominietto, Boris V Afanasyev, Stephen Robinson, Didier BlaiseAbstract:Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-Transplantation cyclophosphamide-based Haploidentical (HAPLO) allogeneic hematopoietic cell Transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) Transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-Transplantation cyclophosphamide-based HAPLO Transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD Transplantation.
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role of naive derived t memory stem cells in t cell reconstitution following allogeneic Transplantation
Blood, 2015Co-Authors: Alessandra Roberto, Luca Castagna, Barbara Sarina, Roberto Crocchiolo, Stefania Bramanti, Veronica Zanon, James E Mclaren, Sara Gandolfi, Paolo Tentorio, I TimofeevaAbstract:Early T-cell reconstitution following allogeneic Transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Posttransplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipulated grafts, but its effect on subsequent immune reconstitution remains undetermined. Here, we show that T memory stem cells (TSCM), which demonstrated superior reconstitution capacity in preclinical models, are the most abundant circulating T-cell population in the early days following Haploidentical Transplantation combined with pt-Cy and precede the expansion of effector cells. Transferred naive, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that posttransplant TSCM originate from naive precursors. Moreover, donor naive T cells specific for exogenous and self/tumor antigens persist in the host and contribute to peripheral reconstitution by differentiating into effectors. Similarly, pathogen-specific memory T cells generate detectable recall responses, but only in the presence of the cognate antigen. We thus define the cellular basis of T-cell reconstitution following pt-Cy at the antigen-specific level and propose to explore naive-derived TSCM in the clinical setting to overcome immunodeficiency. These trials were registered at www.clinicaltrials.gov as #NCT02049424 and #NCT02049580.
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nonmyeloablative conditioning unmanipulated Haploidentical sct and post infusion cy for advanced lymphomas
Bone Marrow Transplantation, 2014Co-Authors: Luca Castagna, Elisa Mauro, Barbara Sarina, Roberto Crocchiolo, Sabine Furst, S Bramanti, Laura Giordano, Lucio Morabito, R Bouabdallah, Diane CosoAbstract:Allo-SCT is regularly performed in advanced lymphoma. Haploidentical family donors are a valuable source of hematopoietic stem cells and transplants from these donors, using T-repleted grafts, has recently been successfully reported. We report on 49 patients with refractory lymphoma who received T-repleted Haploidentical SCT with a non-myeloablative regimen and post-transplant CY. The median time to recover ANC >0.5 × 10e9/L and transfusion independent plt count >20 × 10e9/L was 20 days (range 14-38) and 26 days (range 14-395). The probability to reach ANC >0.5 × 10e9/L at 30 days was 87% and transfusion independent plt count >20 × 10e9/L at 100 days was 87%. The cumulative incidence of grade 2-4 acute GVHD (aGVHD) was 25.6% (95% confidence interval (CI): 12.9-38.3%) and the cumulative incidence of chronic GVHD (cGVHD) was 5.2% (95% CI: 0-12.4%). The median follow-up is 20.6 months (range 12-54), and the projected 2-year OS and PFS were 71 and 63%. The relapse rate was 18.7% (95% CI: 7.6-29.8%) and the median time to relapse was 4.4 months (range 1.1-8.3). At 2 years, cumulative incidence of NRM was 16.3% (95% CI: 5.9-26.8%). T-repleted Haploidentical Transplantation with post-infusion CY is a feasible and effective therapy in the poor prognosis of advanced lymphoma patients.
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bone marrow compared with peripheral blood stem cells for Haploidentical Transplantation with a nonmyeloablative conditioning regimen and post Transplantation cyclophosphamide
Biology of Blood and Marrow Transplantation, 2014Co-Authors: Luca Castagna, Elisa Mauro, Barbara Sarina, Roberto Crocchiolo, Stefania Bramanti, Sabine Furst, Jean El Cheikh, Angela Granata, Catherine Faucher, Bilal MohtyAbstract:Abstract Recently, the administration of high-dose cyclophosphamide (Cy) after T cell–replete Haploidentical stem cell infusion has been reported to be feasible and effective. In the original study, bone marrow (BM) was used as the source of stem cells. Here, we retrospectively analyzed the use of BM versus peripheral blood stem cells (PBSCs) in a cohort of patients receiving Haploidentical T cell–replete Transplantation after a nonmyeloablative conditioning regimen with postinfusion Cy. In the PBSC versus BM groups, the incidence of acute graft-versus-host disease (GVHD) was 33% versus 25%, respectively, and the incidence of chronic GVHD was 13% versus 13%, respectively. The median time to achieve a safe and unsupported absolute neutrophil and platelet count was 20 versus 21 days and 27 versus 29 days, respectively. The incidence of engraftment was also similar in the 2 cohorts. The 1-year nonrelapse mortality rate was 12% versus 22%, respectively ( P = .96). Finally, nonsignificant differences in survival were observed. In conclusion, the use of PBSCs instead of BM after T cell–replete Haploidentical Transplantation did not appear to be detrimental in terms of either GVHD or engraftment rate. PBSCs could be a valid alternative to BM after Transplantation from a Haploidentical donor using postinfusion Cy.
