Anti-Thymocyte Globulin Prophylaxis in Patients With Hematological Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: An Updated Meta-Analysis

Yang, Xue; Li, Dongjun; Xie, Yao

doi:10.3389/fonc.2021.717678

Cited by 5 publications

(7 citation statements)

References 29 publications

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“…T-cell depletion with ATG in addition to standard GvHD prophylaxis has been shown to significantly reduce the occurrence and severity of GvHD in patients undergoing allo-HCT; ATG is also associated with impaired immune reconstitution and increased risk of infections. 46,47 In patients receiving ATG in the current study, the cumulative incidence of the more severe grade C-D aGvHD by Day 100 was lower with defibrotide prophylaxis compared to SOC alone; this difference was maintained through Day 180 post-transplant. There was a slightly higher proportion of mismatched donors with grade C-D aGvHD in the SOC arm (24%) versus the defibrotide prophylaxis arm (13%).…”

Section: Discussionmentioning

confidence: 56%

A phase II, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

et al. 2022

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Acute graft-versus-host disease (aGvHD) is a life-threatening complication typically occurring within 100 days after allogeneic hematopoietic cell transplantation (allo-HCT). This hypothesisgenerating, phase 2, prospective, open-label, randomized study compared defibrotide added to standard-of-care (SOC) GvHD prophylaxis (defibrotide prophylaxis arm) versus SOC alone (SOC arm) to prevent aGvHD post-transplant. This study estimated incidences of aGvHD and was not statistically powered to assess differences among treatment arms. Patients were randomized 1:1 to defibrotide prophylaxis arm (n=79; median age: 57 years, range: 2-69 years) or SOC arm (n=73; median age: 56 years, range: 2-72 years). Patient demographics in the two arms were similar except for conditioning regimen type (myeloablative: defibrotide, 76% vs. SOC, 61%) and stem cell source for allo-HCT (bone marrow: defibrotide, 34% vs. SOC, 26%). In the intent-to-treat primary endpoint analysis, the cumulative incidence of grade B-D aGvHD at Day 100 post-transplant was 38.4% in the defibrotide prophylaxis arm versus 47.1% in the SOC arm (difference: -8.8% [90% confidence interval (CI): -22.5, 4.9]). The difference noted at Day 100 became more pronounced in a subgroup analysis of patients who received antithymocyte globulin (defibrotide: 30.4%, SOC: 47.6%; difference: -17.2% [90% CI: -41.8, 7.5]). Overall survival rates at Day 180 post-transplant were similar between arms, as were the rates of serious treatment-emergent adverse events (defibrotide: 42%, SOC: 44%). While the observed differences in endpoints between the two arms were not substantial, these results suggest defibrotide prophylaxis may add a benefit to currently available SOC to prevent aGvHD following allo-HCT without adding significant toxicities.

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Section: Discussionmentioning

confidence: 56%

A phase II, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

et al. 2022

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“…30 The noted advantage of abatacept over ATG is interesting and should be explored because even though a recent meta-analysis reported that the addition of ATG to GvHD prophylaxis in patients undergoing HSCT resulted in a significantly lower risk of grade III-IV aGvHD, however ATG treatment was correlated with a high incidence of Epstein-Barr virus (EBV) reactivation and did not appear to affect overall survival. 7 Extended studies: nonmalignant HSCT is used to treat nonmalignant diseases affecting the lymphohematopoietic system, particularly sickle cell anemia, which is limited, due to a lack of appropriate donors. 31 Alternative donor transplants with abatacept show promising results in patients suffering from life-threatening nonmalignant hematologic diseases and lacking an HLA-matched sibling donor.…”

Section: Extended Studies: Malignantmentioning

confidence: 99%

Section: Extended Studies: Malignantmentioning

confidence: 99%

“… 4 Anti-lymphocyte antibodies either polyclonal (anti thymocyte globulin) or monoclonal (alemtuzumab) are also being used as GvHD prophylaxis due to their effects on T-cell surface antigens or in vivo T-cell depletion by depleting CD4 lymphocytes. 5 – 7 Recent progress in GvHD pathophysiology research has supplied comprehensive knowledge of associated signaling pathways. Consequently, leading to the development of targeted agents which are under study (Phase II and III trials).…”

Section: Introductionmentioning

confidence: 99%

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Role of abatacept in the prevention of graft-versus-host disease: current perspectives

Ngwube

Rangarajan

Shah

2023

Therapeutic Advances in Hematology

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Administration of abatacept following transplantation has been reported to inhibit graft rejection and graft- versus-host-disease (GvHD) in mouse models associated with allogeneic hematopoietic stem cell transplant (HSCT). This strategy has recently been adopted in clinical practice for GvHD prevention in human allogeneic HSCT and offers a unique approach to optimizing GvHD prophylaxis following alternative donor HSCTs. When combined with calcineurin inhibitors and methotrexate, abatacept had shown to be safe and effective in preventing moderate to severe acute GvHD in myeloablative HSCT using human leukocyte antigen (HLA) unrelated donors. Equivalent results are being reported in recent studies using alternative donors, in reduced-intensity conditioning HSCT and nonmalignant disorders. These observations have led to hypothesizing that even in the setting of increasing donor HLA disparity, abatacept when given with traditional GvHD prophylaxis does not worsen general outcomes. In addition, in limited studies, abatacept have being protective against the development of chronic GvHD through extended dosing and in the treatment of steroid-refractory chronic GvHD. This review summarized all the limited reports of this novels approach in the HSCT setting.

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“…ATG has been studied extensively over the years as GVHD prophylaxis in the setting of MRD, MUD, MMUD, and haploidentical SCT but with differences in terms of patient populations, donors, stem cell source, regimens, timing, dose, formulations, relation to absolute lymphocyte count (60), and planned use of granulocyte colony-stimulating factor (GCSF) (61). Two recent meta-analyses by Kumar et al (62) and Yang et al (63) examined ATG in SCT GVHD prevention. Both metaanalyses suggested that ATG reduced grade II/III and grade III/IV aGVHD and cGVHD without affecting the OS and NRM.…”

Section: Antithymocyte Globulinmentioning

confidence: 99%

Graft-versus-host disease: teaching old drugs new tricks at less cost

Farhan

Holtan

2023

Front. Immunol.

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Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Currently, more patients can receive SCT. This is attributed to the use of reduced intensity regimens and the use of different GVHD prophylaxis that breaks the barrier of human leukocyte antigen, allowing an increase in the donor pool. Once an area with relatively few clinical trial options, there has been an increase in interest in GVHD prophylaxis and treatment, which has led to many US Food and Drug Administration (FDA) approvals. Although there is considerable excitement over novel therapies, many patients may not have access to them due to geographical or other resource constraints. In this review article, we summarize the latest evidence on how we can continue to repurpose drugs for GVHD prophylaxis and treatment. Drugs covered by our review include those that have been FDA approved for other uses for at least 15 years (since 2008); thus, they are likely to have generic equivalents available now or in the near future.

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Anti-Thymocyte Globulin Prophylaxis in Patients With Hematological Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: An Updated Meta-Analysis

Cited by 5 publications

References 29 publications

A phase II, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

A phase II, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

Role of abatacept in the prevention of graft-versus-host disease: current perspectives

Graft-versus-host disease: teaching old drugs new tricks at less cost

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