Fighting against hematological malignancy in China: from unique system to global impact

Lv, Meng; Huang, Xiao‐Jun

doi:10.1007/s11427-015-4926-0

Cited by 10 publications

(7 citation statements)

References 79 publications

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“…D 1 X XLi-Juan HuD 2 X X 1 , D 3 X XXiang-Yu ZhaoD 4 X X 1 , D 5 X XXing-Xing YuD 6 X X 1,2 , D 7 X XMeng LvD 8 X X 1 , D 9 X XTing-Ting HanD 1 0 X X 1 , D 1 1 X XWei HanD 1 2 X X 1 , D 1 3 X XXiao-Jun HuangD 1 4 X X 1,2, * INTRODUCTION Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment strategy for hematologic malignancies [1][2][3][4][5][6]. However, graft-versus-host disease (GVHD) is a common complication after allo-HSCT [7][8][9][10], resulting from the activation, amplification, and secretion of numerous inflammatory factors related to donor alloreactive T cells that damage host tissues and organs, mainly in the gastrointestinal tract, liver, and skin [11].…”

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confidence: 99%

Quantity and Quality Reconstitution of NKG2A+ Natural Killer Cells Are Associated with Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Zhao

et al. 2019

Biology of Blood and Marrow Transplantation

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The immune mechanism underlying graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (HSCT) remains unclear. Natural killer (NK) cells play a crucial role in mediating pathogen-specific immunity and are the first donor-derived lymphocytes reconstituted post-HSCT. However, NK cells vary at different stages after HSCT. Here, we found that the absolute NKG2A subset cell counts and the percentages of NKG2A among NK cells were significantly reduced in GVHD patients after HSCT compared with those from non-GVHD patients. Moreover, the reduction in NKG2A NK cells in post-HSCT GVHD patients was ascribed to increased apoptosis and a decreased proliferation capacity while retaining a strong graft-versus-leukemia effect. In vitro assays showed that co-culture of T cells with NKG2A NK cells significantly reduced IFN-γ secretion by T cells and increased IL-4 secretion. Moreover, the CD25 expression level was decreased, whereas the number of cells with the CD4CD25FOXP3 phenotype was increased. In addition, the NKG2A NK cells induced T cell apoptosis and decreased T cell proliferation during the co-culture process. Importantly, NKG2A NK cells mainly regulated activated but not resting T cells. In vivo assays showed that the serologic IL-10 level was evidently lower in GVHD than in non-GVHD patients, whereas the IL-1β, IFN-γ, and tumor necrosis factor-α levels were higher in GVHD patients. Furthermore, the NKG2A NK cell ratio from GVHD patients was markedly increased by the presence of exogenous IL-10 but not by other cytokines. In contrast, the NKG2A cell ratio from non-GVHD patients was not increased by IL-10. Therefore, post-HSCT GVHD may be ascribed to the reduced induction of NKG2A NK cells by IL-10, which further overactivates T cells.

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confidence: 99%

Quantity and Quality Reconstitution of NKG2A+ Natural Killer Cells Are Associated with Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Zhao

et al. 2019

Biology of Blood and Marrow Transplantation

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“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially from HLA-matched sibling donors (MSD) or matched unrelated donors (MUD), is one of the standard options and possibly the preferred option for individuals with int-risk AML (6)(7)(8)(9)(10). Although emerging data suggest that MSD-HSCT or MUD-HSCT may be superior to chemotherapy alone for the management of int-risk AML (10)(11)(12), the shortage of MSDs and limited availability of MUDs (especially in non-Caucasian populations) prevents large populations from benefiting from allo-HSCT (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

“…Because of the worldwide application of haplo-HSCT, its incidence among allo-HSCT procedures has grown steadily from 3%-5% to more than 15%-18% in Europe and the United States, and there has been a remarkable trends in the replacement of MUD-HSCT by haplo-HSCT (28,29). Meanwhile, the number of haplo-HSCT cases increased at the highest rate to approximately 3,700 cases per year, making it the largest donor source of allo-HSCT (from 37.6% to 56.3%) in China from 2013 to 2017 (14,30).…”

Section: Introductionmentioning

confidence: 99%

Myeloablative Haploidentical Transplantation Is Superior to Chemotherapy for Patients with Intermediate-risk Acute Myelogenous Leukemia in First Complete Remission

Wang

Chang

et al. 2019

Clinical Cancer Research

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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 (ATGþG-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 ¼ 69) or underwent haplo-HSCT (n ¼ 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 ¼ 0.0004 and 80.8% vs. 53.5%; P ¼ 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 ¼ 0.011], OS (HR 0.361; 95% CI, 0.156-0.832; P ¼ 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057-0.459; P ¼ 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. Conclusions: Myeloablative haplo-HSCT with ATGþG-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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“…To perform HSC grafts for haplo-HSCT, some centers use bone marrow (BM) grafts, and some centers use G-CSF-mobilized BM (GBM) or G-CSF-mobilized PBSCs (GPBs). Over the past 15 years, by using a combination of GBM and GPBs, as well as antithymocyte globulin (ATG) administration for the prophylaxis of graft-versus-host disease (GVHD) and graft rejection, the Beijing group initiated one of the earliest clinical trials to explore unmanipulated myeloablative haploidentical blood and marrow transplantation (HBMT) for leukemia (Huang et al, 2006;Lv and Huang, 2015). However, which type of grafts would be best for haplo-HSCT is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Improved clinical outcomes of rhG-CSF-mobilized blood and marrow haploidentical transplantation compared to propensity score-matched rhG-CSF-primed peripheral blood stem cell haploidentical transplantation: a multicenter study

Zhao

Gao

Zhang

et al. 2016

Sci. China Life Sci.

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The effects of haploidentical rhG-CSF-mobilized blood and marrow transplantation (HBMT) on hematological malignances are well established. Previous prospective single-center studies have demonstrated better survival after HBMT versus haploidentical rhG-CSF-mobilized peripheral blood stem cell transplantation (HPBSCT) for acute leukemia (AL) not in remission (NR) or in more than the second complete remission (>CR2). To test the hypothesis that HBMT is still superior to HPBSCT for patients with AL, multiple myeloma (MM), or non-Hodgkin lymphoma (NHL) in CR1/CR2 and for patients with chronic myeloid leukemia in the first and second chronic phase lacking a matched donor, we designed a propensity score method-based multicenter study. Hematopoietic recovery, acute graft-versus-host disease (aGVHD), and chronic GVHD were comparable between the HBMT group (n=168) and the HPBSCT group (n=42). No significant differences were found in non-relapse mortality rate (20.17%±3.58% and 27.24%±7.16%, P=0.18) or relapse rate (19.96%±3.72% and 28.49%±8.25%, P=0.32) between the HBMT group and the HPBSCT group. HBMT recipients had better overall survival (65.0%±4.2% and 54.2%±8.3%, P=0.037) and disease-free survival (59.9%±4.6% and 44.3%±8.7%, P=0.051). Multivariate analysis showed that HPBSCT was associated with poorer DFS (HR (95%CI), 1.639 (0.995-2.699), P=0.052). Our comparisons showed that HBMT was superior to HPBSCT as a post-remission treatment for patients lacking an identical donor. HBMT, GPB, Beijing Protocol, HSCTCitation:

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Fighting against hematological malignancy in China: from unique system to global impact

Cited by 10 publications

References 79 publications

Quantity and Quality Reconstitution of NKG2A+ Natural Killer Cells Are Associated with Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Quantity and Quality Reconstitution of NKG2A+ Natural Killer Cells Are Associated with Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Myeloablative Haploidentical Transplantation Is Superior to Chemotherapy for Patients with Intermediate-risk Acute Myelogenous Leukemia in First Complete Remission

Improved clinical outcomes of rhG-CSF-mobilized blood and marrow haploidentical transplantation compared to propensity score-matched rhG-CSF-primed peripheral blood stem cell haploidentical transplantation: a multicenter study

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