High Level of CD4+CD25+CD127- Treg Cells in Donor Graft is Associated with a Low Risk of aGVHD after allo-HSCT for Children with Hematologic Malignancies

Zhang, Fang; Zhu, Hong-Jian; Changying, Luo; Wang, Jianmin; Chengjuan, Luo; Xu, Kangli; Chen, Jing

doi:10.4172/2157-7013.1000148

Cited by 2 publications

(4 citation statements)

References 29 publications

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“…We also analyzed the effect of patient's age, gender, diagnosis, duration from diagnosis to transplant, conditioning regimen and gender mismatch on the severity of aGVHD. There was no statistical difference for above parameters between the two groups and these observations were similar to the studies by Denby et al [17] and Fang et al [11].…”

Section: Discussionsupporting

confidence: 91%

“…We did not find any significant association of Treg cell dose or Treg/CD4 ratio with CMV reactivation and relapse. Concurrent result regarding Treg cell dose and CMV reactivation or relapse were observed in several other studies [11,17,18].…”

Section: Discussionsupporting

confidence: 58%

“…Several other studies also demonstrate the association between higher counts of Treg cells in donor graft and reduced incidence of grade II-IV aGVHD in allo-HSCT [9,10,18]. Recently, in a study on a cohort of 50 children with hematological malignancies undergoing allo-HSCT, Fang et al [11], found that graft Treg cells were significantly lower in children with grade II-IV aGVHD as compared to those with grade 0-I aGVHD. In contrast to above studies, Stanzani et al [19] found that CD4?…”

Section: Discussionmentioning

confidence: 91%

“…Treg cells in the donor graft negatively correlated with the incidence of GVHD without any difference in the incidence of relapse. Recently, in a cohort of 50 children with hematological malignancies, Fang et al [11], reported that lesser number of Treg cells in donor grafts were associated with grade II-IV aGVHD compared to those with grade 0-I aGVHD. In this study, we enumerated Treg cells by flowcytometry and studied its correlation with the severity of aGVHD in post allo-HSCT patients.…”

Section: Introductionmentioning

confidence: 99%

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T Regulatory Cells in Donor Grafts May Predict the Severity of Acute Graft Versus Host Disease After Matched Sibling Donor Allogenic Peripheral Blood Stem Cell Transplantation

Chandra

Singh

Deka

et al. 2019

Indian J Hematol Blood Transfus

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Acute graft-versus-host disease (aGVHD) and relapse are major issues for patients undergoing allogenic hematopoietic stem cell transplant (allo-HSCT). T-regulatory (Treg) cells in the donor graft are negatively correlated with the incidence of aGVHD without any impact on relapse. In this study to determine the association of Treg cells with aGVHD in allo-HSCT patients. Thirty-two patients with hematological disorders, who underwent allo-HSCT. Twenty-nine patients who achieved engraftment were enrolled in the study. Treg cells were quantified in donor graft by flowcytometry and were assessed for their association with aGVHD and other clinical outcomes. Fifteen of 29 patients developed aGVHD. According to the occurrence and severity of aGVHD, patients were divided into two groups: 20 (68.9%) patients with grade 0-I aGVHD and 9 (31.1%) patients with grade II-IV aGVHD. Treg cells/CD4 ratio was significantly higher in the grade 0-I aGVHD group than in grade II-IV aGVHD group, (p = 0.0002). We could not find the association of CD34 dose (p = 0.55) or CD3 dose (p = 0.57) with the severity of aGVHD. Higher Treg cells/CD4 ratio in donor graft was associated with less severe aGVHD. Though more studies are needed, Treg cells/CD4 ratio may be used as a predictive marker for severity of aGVHD in post allo-HSCT.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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T Regulatory Cells in Donor Grafts May Predict the Severity of Acute Graft Versus Host Disease After Matched Sibling Donor Allogenic Peripheral Blood Stem Cell Transplantation

Chandra

Singh

Deka

et al. 2019

Indian J Hematol Blood Transfus

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Modalities to Improve Cord Blood Engraftment

Yurdakul¹

2014

J Stem Cell Res Ther

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Umblical cord blood (UCB) is one of the major sources of Hematopoietic Stem Cell Transplantation (HSCT) with increasing use in clinical practice. UCB can be a life saver for patients who do not have a matched unrelated adult donor or for patients who are in need of an urgent transplantation. Various factors make UCB a significant source of Hematopoietic Stem Cells (HSCs), including ease of procurement and lack of donor attrition, with the ability to process and long term storage of donor cells. Importantly, UCB donations can be used right away without the need for a "perfect" HLA match, thereby increasing donor access to HSCT, particularly for minority and mixed ethnicity patients, for whom a suitably matched related or unrelated donor may be difficult to locate. The major limitation of UCB is the quantity of cells to be infused. Although high proliferative potential allows one log less use of HSCs (HSC<10 5 /kg) compared to bone marrow (BM) or peripheral blood mononuclear cells (PBSC), even this amount cannot be reached in the majority of patients under donor search. When total nucleated cell (TNC) and CD34+ cell doses in UCB grafts are analyzed, a high correlation is observed with the rate of neutrophil and platelet engraftment, the incidence of graft failure and early transplant-related complications. It has been shown that UCB grafts with more than 3/6 HLA mismatches and with cell doses under the defined minimum threshold lead to higher transplantation related mortality (TRM). Especially when adult cord blood transplantation (UCBT) is the subject, providing units with enough cells remains the major drawback.Despite certain efforts, there is still an unmet need for increasing HSC cell dose and/or stimulating engraftment without loss of their long term repopulating (LTR) potential and reducing graft versus host disease (GVHD). Intrinsic and extrinsic cellular factors have been proven to act roles in HSC expansion thus justifying their role in in vitro and ex vivo culture conditions. Attempts to regulate these factors through ex vivo expansion methods aim to overcome insufficient cell numbers while methods promoting HSC homing is in favor of the latter. Combination of both appear to work synergistically. Induction or adoptive transfer of UCB derived immune cells particularly Natural Killer (NK) cells and regulatory T cells (T reg) with or without cytokines are also effective approaches for gaining better engraftment levels after UCBT. All of these approaches have been denoted as "successful" in pre-clinical in vitro and animal studies. Many of them have also been tested in early/later phase clinical trials resulting in encouraging results. We aim to review the current knowledge on UCB expansion and engraftment enhancer methods, a very rapidly improving field particularly in the last decade.Eltrombopag enhanced expansion of HSC/HPC of human UCB in vivo and in vitro, and promoted multi-lineage hematopoiesis through the expansion of BM HSC/HPC of human UCB in vivo. A novel c-MPL agonist, a small molecule, ...

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High Level of CD4+CD25+CD127- Treg Cells in Donor Graft is Associated with a Low Risk of aGVHD after allo-HSCT for Children with Hematologic Malignancies

Cited by 2 publications

References 29 publications

T Regulatory Cells in Donor Grafts May Predict the Severity of Acute Graft Versus Host Disease After Matched Sibling Donor Allogenic Peripheral Blood Stem Cell Transplantation

T Regulatory Cells in Donor Grafts May Predict the Severity of Acute Graft Versus Host Disease After Matched Sibling Donor Allogenic Peripheral Blood Stem Cell Transplantation

Modalities to Improve Cord Blood Engraftment

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