Zujun Jiang

General Hospital of Guangzhou Military Command

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Haowen Xiao

Sichuan University

Qifa Liu

Southern Medical University

Yonghua Li

General Hospital of Guangzhou Military Command

Yan Pang

General Hospital of Guangzhou Military Command

Yang Gao

Jining Medical University

Dongjun Lin

The Seventh Affiliated Hospital of Sun Yat-sen University

Zenghui Liu

People’s Hospital of Wenshan Prefecture

Zhiping Fan

Nanfang Hospital

Danian Nie

Sun Yat-sen University

Yang Xiao

Central South University

Cooperative Institutions

Southern Medical University

Nanfang Hospital

Sun Yat-sen University

General Hospital of Guangzhou Military Command

Chinese Academy of Medical Sciences & Peking Union Medical College

Chinese Academy of Sciences

Sichuan University

Huazhong University of Science and Technology

University of Chinese Academy of Sciences

Guangzhou Medical University

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Co-transplantation of mesenchymal stem cells makes haploidentical HSCT a potential comparable therapy with matched sibling donor HSCT for patients with severe aplastic anemia

Therapeutic Advances in Hematology (2020)

Zenghui Liu Xiaoxiong Wu Shunqing Wang Linghui Xia Haowen Xiao

The application of haploidentical hematopoietic stem cell transplantation (HSCT) with mesenchymal stem cell (MSC) infusion as a treatment regimen for severe aplastic anemia (SAA) has been reported to be efficacious in single-arm trials. However, it is difficult to assess without comparing the results with those from a first-line, matched-sibling HSCT. Herein, we retrospectively reviewed 91 patients with acquired SAA. They received HSCT from haploidentical donors combined with MSC transfer (HID group). We compared these patients with 103 others who received first-line matched-sibling HSCT (MSD group) to evaluate relative treatment efficacy. Compared with the patients in the MSD group, those in the HID group presented with higher incidences of grades II–IV and III–IV acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) ( p < 0.05). However, the incidence of myeloid and platelet engraftment, graft failure, poor graft function, and extensive cGvHD were comparable for both groups. The median follow-up was 36.6 months and the 3-year overall survival rate was similar for both groups (83.5% versus 79.1%). Univariate and multivariate analyses revealed that time intervals greater than 4 months from diagnosis to transplantation, experienced graft failure, poor graft function, or grade III–IV aGvHD were significantly associated with adverse outcomes. All HID patients received MSC co-transplantation with hematopoietic stem cells. However, the infused MSCs were derived from umbilical cord (UC-MSC group; 43 patients) or bone marrow (BM-MSC group; 48 patients) and were administered at different medical centers. We first compared the outcomes between the two groups and detected that the BM-MSC group exhibited lower incidences of grade III–IV aGvHD and cGvHD ( p < 0.05). This study suggests that co-transplantation of hematopoietic and MSCs significantly reduces the risk and incidence of graft rejection and may effectively improve overall survival in patients with SAA even in the absence of closely related histocompatible donor material.

Aplastic anemia

Univariate analysis

10.1177/2040620720965411

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Citations (14)

Allogeneic Bone-Marrow-Derived Mesenchymal stromal Cells Expanded in vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial

Stem Cells Translational Medicine (2017)

Yan Pang Haowen Xiao Hang Zhang Zenghui Liu Li Li

Aplastic anemia

10.1002/sctm.12206

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Citations (4)

Comparison of Two Strategies for Prophylactic Donor Lymphocyte Infusion in Patients With Refractory/Relapsed Acute Leukemia

Frontiers in Oncology (2021)

Qiongqiong Su Zhiping Fan Fen Huang Na Xu Danian Nie

Prophylactic donor lymphocyte infusion (pDLI) could reduce relapse in patients with refractory/relapsed acute leukemia (RRAL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but optimal timing of pDLI remains uncertain. We compared the outcomes of two strategies for pDLI based on time from transplant and minimal residual disease (MRD) status in patients with RRAL. For patients without grade II–IV acute graft-versus-host disease (aGVHD) on day +60, pDLI was given on day +60 regardless of MRD in cohort 1, and was given on day +90 unless MRD was positive on day +60 in cohort 2. A total of 161 patients with RRAL were enrolled, including 83 in cohort 1 and 78 in cohort 2. The extensive chronic GVHD (cGVHD) incidence in cohort 2 was lower than that in cohort 1 (10.3% vs. 27.9%, P = 0.006) and GVHD-free/relapse-free survival (GRFS) in cohort 2 was superior to that in cohort 1 (55.1% vs. 41.0%, P = 0.042). The 2-year relapse rate, overall and leukemia-free survival were comparable between the two cohorts (29.0% vs. 28.2%, P = 0.986; 63.9% vs. 64.1%, P = 0.863; 57.8% vs. 61.5%, P = 0.666). Delaying pDLI to day +90 based on MRD for patients with RRAL undergoing allo-HSCT could lower extensive cGVHD incidence and improve GRFS without increasing incidence of leukemia relapse compared with pDLI on day +60.

Minimal Residual Disease

Refractory (planetary science)

Donor lymphocyte infusion

Cumulative incidence

10.3389/fonc.2021.554503

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Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial

Stem Cells Translational Medicine (2017)

Yan Pang Haowen Xiao Hang Zhang Zenghui Liu Li Li

We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy-four patients from seven centers received allogeneic BM-MSCs at a dose of 1-2 × 106 cells/kg per week for 4 weeks. Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first cells infusion. Patients with response at 1 month continued to receive four infusions. All patients were evaluable. The overall response rate was 28.4% (95% confidence interval, 19%-40%), with 6.8% complete response and 21.6% partial response. The median times to response of leukocytic, erythrocytic, and megakaryocytic linages were 19 (range, 11-29), 17 (range, 12-25), and 31 (range, 26-84) days, respectively. After median follow-up of 17 months, overall survival was 87.8%. Seven patients developed transitory and mild headache and fever, but no other adverse events were observed. Antithymocyte globulin used in previous treatment and no activated infection throughout treatment were predictors for response. Allogeneic BM-MSCs infusion is a feasible and effective treatment option for refractory AA. The trial was registered at www.clinicaltrials.gov as NCT00195624. Stem Cells Translational Medicine 2017;6:1569-1575.

Aplastic anemia

10.1002/sctm.16-0227

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Citations (24)

Retraction Note to: Neutropenia and invasive fungal infection in patients with hematological malignancies treated with chemotherapy: a multicenter, prospective, non-interventional study in China

Tumor Biology (2014)

Yonghua Li Wenning Xu Zujun Jiang Yang Gao Yan Pang

10.1007/s13277-014-2603-8

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間葉系幹細胞の同時移植は,重度再生不良性貧血患者に対するマッチド同胞ドナーHSCTによる潜在的な比較可能な治療を可能にする【JST・京大機械翻訳】

Therapeutic Advances in Hematology (2020)

Zenghui Liu Xiaoxiong Wu Shunqing Wang Linghui Xia Haowen Xiao

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Haploidentical hematopoietic SCT using helical tomotherapy for total-body irradiation and targeted dose boost in patients with high-risk/refractory acute lymphoblastic leukemia

Bone Marrow Transplantation (2018)

Zujun Jiang Junsong Jia Chunyan Yue Yan Pang Zenghui Liu

Total body irradiation

Tomotherapy

Refractory (planetary science)

Acute lymphocytic leukemia

10.1038/s41409-017-0049-5

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Citations (18)

Haploidentical versus HLA-matched sibling transplantation for refractory acute leukemia undergoing sequential intensified conditioning followed by DLI: an analysis from two prospective data

Journal of Hematology & Oncology (2020)

Sijian Yu Fen Huang Zhiping Fan Li Xuan Danian Nie

Compared with HLA-matched sibling donor (MSD) transplant, the outcomes of haploidentical donor (HID) transplant for refractory acute leukemia need to be further explored. In this study, we compared the outcomes of HID with MSD for refractory acute leukemia.This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Two hundred and seventy-eight patients with refractory acute leukemia were enrolled in this study, including 119 in HID group and 132 in MSD group. Sequential intensified conditioning was employed in all patients, and donor lymphocyte infusion (DLI) was administered in patients in the absence of active GVHD and according to minimal residual disease (MRD) from day + 60 post-transplantation for preventing relapse.The complete remission of leukemia by day + 30 post-transplant were 94% and 93%, respectively, in HID and MSD groups (p = .802). The 1-year incidence of grades II-IV acute GVHD was 62% and 54% (p = .025), and 3-year incidence of chronic GVHD was 55% and 55% (p = .789), respectively, in two groups. HID transplant had lower incidence of first episode of MRD positivity and relapse than MSD transplant (28% vs 45%, p = .006; 26% vs 38%, p = .034). There was higher infection-related mortality in HID than MSD (8% vs 2%, p = .049) within the first 100 days' post-transplant. The 5-year overall survival was 46% and 42% (p = .832), respectively; the 5-year disease-free survival was 43% and 39% (p = .665), in HID and MSD groups, respectively.HID transplant has lower relapse, but higher infection-related mortality and similar survival rates in refractory acute leukemia by the strategy of sequential intensified conditioning followed by DLI compared with MSD transplant.

Refractory (planetary science)

Cumulative incidence

Hematology

Minimal Residual Disease

10.1186/s13045-020-00859-5

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Citations (44)

Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph– high-risk B-cell acute lymphoblastic leukemia

Chinese Medical Journal (2021)

Menglin Fan Yu Wang Ren Lin Tong Lin Fen Huang

Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P = 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P = 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P = 0.041), respectively, in the HID and MSD groups.HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.ClinicalTrials.gov: NCT01883180, NCT02673008.

Cumulative incidence

Minimal Residual Disease

Clinical endpoint

10.1097/cm9.0000000000001852

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Following up Observation of Change in Immunologic Function in 52 Patients Exposed to Long-term Low Dose of ~(192)Ir Radiation

Military Medical Journal of South China (2007)

Zujun Jiang

Objective To observe the change in the immunologic function in patients exposed to long-term 192 Ir low dose radiation. Methods Fifty-two patients were accidentally exposed to 192Ir low dose radiation from May 9 to July 19, 2002. The fifty-two patients were divided into both the groups A and B according radiation dose estimated by the standard dose-response curves established via the analyses of dicentric rplus rings(dic+ r) and cytokinesis-block micronuclei analysis. There were 29 patients exposed to 0. 05-0. 19Gy in group A, and there were 23 patients exposed to 0. 20-0. 66Gy in group B. The contents of serum IgG, IgA and IgM, T lymphocyte transformation rate, and the positive rate of CD 3, CD 4, CD 8 and NK cells were determined 3 years after the radiation in all the patients. Results The contents of serum IgA and IgM in both the groups A and B were insignificantly different from those in the control group (P0. 05), but the contents of serum IgG, C3 and C4 were significantly lower in group B than those in the control group(P0. 01). The positive rates of CD 3, CD 4, CD 8 and NK cells, and lymphocyte transformation rate were significantly lower in both the groups A and B than those in the control group (P0. 01). The positive rates of CD 3, CD 4, CD 8 and NK cells, and lymphocyte transformation and the value of CD4+ /CD8+ in the group A were insignificantly different from those in group B (P0. 05). Conclusion No simulative effect of long-term low dose radiation on immunologic system is observed 3 years after the radiation. On the contrary, it is suggested the long-term dose radiation can inhibit the cellular immune response in the patients. It is very important to follow up the irradiated persons for long time.

Dicentric chromosome

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