ATG in allogeneic stem cell transplantation: standard of care in 2017? Point

Bacigalupo, Andrea

doi:10.1182/bloodadvances.2016001560

Cited by 17 publications

(11 citation statements)

References 22 publications

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“…ATG has been widely used to decrease the incidence of GVHD (31), however, because of T-cell depletion, ATG is also associated with relapse (32). The optimal dose of ATG depends on transplant characteristics, such as type of donor, and may range from 2.5 to 30 mg/kg (33). ATG has beneficial effects in preventing GVHD, although it delays immune reconstitution, promoting an increased risk of EBV reactivation, and potentially EBV-associated lymphoproliferative disease (34).…”

Section: Discussionmentioning

confidence: 99%

Association of Epstein‑Barr virus infection with allogeneic hematopoietic stem cell transplantation in patients in Portugal

et al. 2018

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The identification of patients at higher risk of developing Epstein-Barr virus (EBV) infection in hematopoietic stem cell transplants (HSCT) is useful for the prevention of EBV-associated diseases A prospective observational study was developed that included 40 patients (27 male and 13 females, with mean age of 32.2±1.5 years old) undergoing allogeneic-HSCT between January and December 2015. EBV was examined in whole blood samples collected during routine procedures at day (D)+30, D +60, +90, D+120, D+150 and D+180 post-transplant. EBV was detected, at least once during the follow-up period in 70.0% of our patients. Results indicated that patients with unrelated donors had increased risk of developing EBV infection at D+60 and D+150 (OR=3.9, P=0.058; OR=8.0, P=0.043; respectively). Moreover, myeloablative conditioning (OR=4.3, P=0.052), anti-thymocyte globulin use (OR=12.0, P=0.030) and graft-vs.-host disease (OR=6.7, P=0.032) were associated with EBV infection at D+60, D+150 and D+90, respectively. In our series, none of these patients developed post-transplant lymphoproliferative disease. To the best of our knowledge, the present study is the first study to report EBV infection in patients undergoing aHSCT from Portugal. The study revealed that EBV infection is associated with different factors. These findings provide evidence towards the identification of high-risk patients for EBV-infection and associated disease.

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Section: Discussionmentioning

confidence: 99%

Association of Epstein‑Barr virus infection with allogeneic hematopoietic stem cell transplantation in patients in Portugal

et al. 2018

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“…Several prospective randomized trials and subsequent meta-analyses supported the efficacy of prophylactic in vivo T-cell depletion with rabbit anti-thymocyte globulin (ATG) to prevent both aGVHD and cGVHD [ 8 – 14 ]. However, the benefits in terms of prevention of GVHD did not translate into a survival improvement [ 15 – 17 ]. The use of ATG has been associated with delayed immune reconstitution, which might increase the risk of opportunistic infections and impair graft-versus-tumor responses [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of anti-thymocyte globulin dose for graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation from matched unrelated donors: a multicenter experience

et al. 2021

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Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6–7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.

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“…In the CNI-era, four RCT evaluated CNI/MTX prophylaxis ± ATG. 24 In the first, using horse ATG, a reduction in aGvHD was offset by higher rates of infection with no difference in NRM or OS; however, there was a reduction in severe chronic GvHD. 25,26 In the second, using rabbit ATG, 27,28 and the third, mainly using PBSC grafts, there was no effect on aGvHD, with a reduction in cGvHD.…”

Section: In Vivo T-cell Depletion/modulationmentioning

confidence: 97%

Translational and clinical advances in acute graft-versus-host disease

Gooptu

Koreth

2020

haematol

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Acute graft-versus-host disease (aGvHD) is induced by immunocompetent alloreactive T lymphocytes in the donor graft responding to polymorphic and non-polymorphic host antigens and causing inflammation in primarily the skin, gastrointestinal tract and liver. aGvHD remains an important toxicity of allogeneic transplantation, and the search for better prophylactic and therapeutic strategies is critical to improve transplant outcomes. In this review, we discuss the significant translational and clinical advances in the field which have evolved based on a better understanding of transplant immunology. Prophylactic advances have been primarily focused on the depletion of T lymphocytes and modulation of T-cell activation, proliferation, effector and regulatory functions. Therapeutic strategies beyond corticosteroids have focused on inhibiting key cytokine pathways, lymphocyte trafficking, and immunologic tolerance. We also briefly discuss important future trends in the field, the role of the intestinal microbiome and dysbiosis, as well as prognostic biomarkers for aGvHD which may improve stratification-based application of preventive and therapeutic strategies.

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ATG in allogeneic stem cell transplantation: standard of care in 2017? Point

Cited by 17 publications

References 22 publications

Association of Epstein‑Barr virus infection with allogeneic hematopoietic stem cell transplantation in patients in Portugal

Association of Epstein‑Barr virus infection with allogeneic hematopoietic stem cell transplantation in patients in Portugal

Impact of anti-thymocyte globulin dose for graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation from matched unrelated donors: a multicenter experience

Translational and clinical advances in acute graft-versus-host disease

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