Defibrotide combined with triple therapy including posttransplant cyclophosphamide, low dose rabbit anti-t-lymphocyte globulin and cyclosporine is effective in prevention of graft versus host disease after allogeneic peripheral blood stem cell transplantation for hematologic malignancies

Akpınar, Seval; Kayıkçı, Ömür; Tekgündüz, Emre

doi:10.1016/j.transci.2022.103367

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…The cumulative incidence of acute grade III–IV GVHD and moderate/severe chronic GVHD requiring 1-yr systemic immunosuppression was 20.6% and 5.3%, respectively. Relapse-free mortality, GVHD relapse-free survival, and overall survival in the 1-yr study cohort were 21.1%, 44.7%, and 57.9%, respectively ( 34 ). Strouse et al found notable differences in the cumulative incidence of grade II–IV acute GVHD at day 100 post-HCT in patients who received defibrotide versus those who did not receive defibrotide (23.1% versus 37.7%; difference, −14.6 [95% CI: −33.1, 3.9]) ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Defibrotide impact on the acute GVHD disease incidence in pediatric hematopoietic stem cell transplant recipients

et al. 2023

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Despite advances in acute graft-versus-host disease (aGVHD) prophylaxis, current pharmacological approaches fail to prevent aGVHD. The protective effect of defibrotide on GVHD incidence and GVHD-free survival has not been sufficiently studied. 91 pediatric patients included in this retrospective study were divided into two groups based on defibrotide use. We compared the incidence of aGVHD and chronic GVHD-free survival between the defibrotide and control groups. The incidence and severity of aGVHD were significantly lower in patients who received defibrotide prophylactic administration than in the control group. This improvement was observed in the liver and intestinal aGVHD. No defibrotide prophylaxis benefit was observed in the prevention of chronic GVHD. The pro-inflammatory cytokine levels were significantly higher in the control group. Our findings suggest that prophylactic administration of defibrotide in pediatric patients significantly reduces the incidence and severity of aGVHD, with a modification of cytokine pattern, both strongly coherent with the protective drug’s action. This evidence adds to pediatric retrospective studies and preclinical data suggesting a possible defibrotide role in this setting.

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Section: Discussionmentioning

confidence: 99%

Defibrotide impact on the acute GVHD disease incidence in pediatric hematopoietic stem cell transplant recipients

et al. 2023

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“…In support of a synergistic effect of defibrotide with other immunosuppressive agents, results from a preliminary study suggest that defibrotide prophylaxis combined with ATG, post-transplant cyclophosphamide, and CSA may be an effective strategy for preventing aGvHD. 52 Furthermore, the role of cell subsets other than T cells, such as endothelial cells, in the pathophysiology of GvHD might be more pronounced in the absence of T lymphocytes, as it occurs with natural killer cell and killer Ig-like receptor disparities in the haploidentical transplant setting. 53 The potential benefits of defibrotide in lowering the incidence of aGvHD, most commonly occurring in the first 100 days following HCT, may reflect defibrotide's mechanism of action, especially its anti-inflammatory and endothelial protective properties, along with the suppression of heparanase gene expression.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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Perspective on oral medication adherence among patients with acute graft-versus-host disease: a qualitative descriptive study

Visintini,

Lucchetta,

Venturini

et al. 2024

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Purpose Despite the importance of adherence to immunosuppressants (IMMs) after an allogeneic haematopoietic stem cell transplant (HSCT) for the treatment of acute graft-versus-host disease (aGvHD), no studies to date have reported the experiences of such patients concerning medication adherence (MA). Therefore, the aim of the study was to explore the perspective on MA to immunosuppressive oral therapy among allogeneic HSCT patients with aGvHD. Methods A qualitative descriptive study following a reflexive thematic analysis methodological approach was performed involving a purposive sample of 16 patients with aGvHD who were being cared for in the outpatient setting of a bone marrow transplant centre and were willing to participate. Semi-structured audio-recorded interviews were conducted, transcribed verbatim and thematically analysed; member checking was performed. COnsolidated criteria for REporting Qualitative research (COREQ) and the ESPACOMP Medication Adherence Reporting Guideline were followed. Results Participants aged 25–74 years and mostly males (62.5%) were recruited for this study; 56.2% developed grade I, 37.5% grade II and 6.3% grade III aGvHD; 56.2% were receiving treatment with both cyclosporine and prednisone. Patients' perspectives have been summarised into four themes, named: “Transiting from an external obligation to a habit”; “Being in the middle between the negative and positive effects of the IMMs”; “Failure to systematically respect the rules”; and “Adopting personal strategies to become adherent”. After difficulties with the perception of feeling obliged, patients became used to adhering to IMMs. Although there were failures in systematically taking the medication correctly and there were episodes of non-adherence, the adoption of personal strategies helped patients to become adherent to their medication schedules. Conclusions MA in patients with aGvHD is a complex behaviour and is often a challenge. These results can help healthcare professionals and centres to understand how best to design tailored strategies and behavioural interventions to maximise patients’ MA to IMMs.

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Defibrotide combined with triple therapy including posttransplant cyclophosphamide, low dose rabbit anti-t-lymphocyte globulin and cyclosporine is effective in prevention of graft versus host disease after allogeneic peripheral blood stem cell transplantation for hematologic malignancies

Cited by 4 publications

References 40 publications

Defibrotide impact on the acute GVHD disease incidence in pediatric hematopoietic stem cell transplant recipients

Defibrotide impact on the acute GVHD disease incidence in pediatric hematopoietic stem cell transplant recipients

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

Perspective on oral medication adherence among patients with acute graft-versus-host disease: a qualitative descriptive study

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