Impact of Thymoglobulin by Stem Cell Source (Peripheral Blood Stem Cell or Bone Marrow) After Myeloablative Stem Cell Transplantation From HLA 10/10-Matched Unrelated Donors

Ravinet, Aurélie; Cabrespine, Aurélie; Socié, Gérard; Milpied, Noël; Yakoub-Agha, Ibrahim; Nguyen, Stephanie; Michallet, Mauricette; Ménard, Anne Lise; Maillard, Natacha; Mohty, Mohamad; Suarez, Félipe; Huynh, Anne; Marchand, Tony; Deteix, Clémence; Jp, Cassuto; Maury, Sébastien; Chevallier, Patrice; Reman, Oumédaly; Latour, Régis Peffault de; Bay, Jacques Olivier

doi:10.1097/tp.0000000000000976

Cited by 13 publications

(6 citation statements)

References 34 publications

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“…On the other hand, Ravinet et al reported no significant impact of ATG in MUD BMSC. In this study various total doses of ATG were used at the discretion of the attending physician (range <5 ->10 mg/kg, only 10 patients received ATG less than 5 mg/kg) (38). In both studies Thymoglobuline was used, as in our study.…”

Section: Discussionmentioning

confidence: 99%

Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival

Ali¹,

Grønvold²,

Remberger³

et al. 2021

Clinical Lymphoma Myeloma and Leukemia

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Section: Discussionmentioning

confidence: 99%

Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival

Ali¹,

Grønvold²,

Remberger³

et al. 2021

Clinical Lymphoma Myeloma and Leukemia

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“…Indeed, two recent studies revealed a greater benefit of ATG in PBSCT than in BMT [38,44]. An explanation for this finding may be the higher burden of severe cGVHD following PBSCT compared to BMT in case of T cell-replete, ATG-free transplantation.…”

Section: Discussionmentioning

confidence: 99%

HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation

et al. 2017

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Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD. Congruously, we have previously reported favorable outcomes in C1/1 recipients after ATG-based transplants in a monocentric analysis. Here, within an extended cohort, we test the hypothesis that incorporation of ATG for GVHD prophylaxis may improve survival particularly in HSCT recipients with at least one C1 KIR-ligand. Retrospectively, 775 consecutive allogeneic (excluding haploidentical) HSCTs were analyzed, including peripheral blood and bone marrow grafts for adults with hematological diseases at two Austrian HSCT centers. ATG-Fresenius/Grafalon, Thymoglobuline, and alemtuzumab were applied in 256, 87, and 7 transplants, respectively (subsequently summarized as “ATG”), while 425 HSCT were performed without ATG. Median follow-up of surviving patients is 48 months. Adjusted for age, disease-risk, HLA-match, donor and graft type, sex match, cytomegalovirus serostatus, conditioning intensity, and type of post-grafting GVHD prophylaxis, Cox regression analysis of the entire cohort (n = 775) revealed a significant association of ATG with decreased non-relapse mortality (NRM) (risk ratio (RR), 0.57; p = 0.001), and overall mortality (RR, 0.71; p = 0.014). Upon stratification for HLA-C KIR-L, the greatest benefit for ATG emerged in C1/1 recipients (n = 291), by reduction of non-relapse (RR, 0.34; p = 0.0002) and overall mortality (RR, 0.50; p = 0.003). Less pronounced, ATG decreased NRM (RR, 0.60; p = 0.036) in HLA-C group 1/2 recipients (n = 364), without significantly influencing overall mortality (RR, 0.70; p = 0.065). After exclusion of higher-dose ATG-based transplants, serotherapy significantly improved both NRM (RR, 0.54; p = 0.019; n = 322) and overall mortality (RR, 0.60; p = 0.018) in C1/2 recipients as well. In both, C1/1 (RR, 1.70; p = 0.10) and particularly in C1/2 recipients (RR, 0.94; p = 0.81), there was no statistically significant impact of ATG on relapse incidence. By contrast, in C2/2 recipients (n = 121), ATG neither reduced NRM (RR, 1.10; p = 0.82) nor overall mortality (RR, 1.50; p = 0.17), but increased the risk for relapse (RR, 4.38; p = 0.02). These retrospective findings suggest ATG may provide a survival benefit in recipients with at least one C1 group KIR-L, by reducing NRM without significantly increasing the relapse risk.

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“…Regarding ATG, Ravinet et al [55] reported that the addition of ATG after a MAC regimen in patients with acute leukemia and MDS transplanted from a well-matched unrelated donor (10/10) was found to significantly reduce aGvHD and cGvHD, and improve graft-versus-host disease-free, relapse-free survival only after PBSC but not after BM transplantation. Survival, relapse, or NRM were not affected by ATG administration.…”

Section: Summary Of Evidencementioning

confidence: 99%

Rabbit ATG/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel

Bonifazi

Rubio

Bacigalupo

et al. 2020

Bone Marrow Transplant

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This collaborative initiative aimed to provide recommendations on the use of polyclonal antithymocyte globulin (ATG) or anti-T lymphocyte globulin (ATLG) for the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). A comprehensive review of articles released up to October, 2018 was performed as a source of scientific evidence. Fourteen clinically relevant key questions to the domains indication, administration, and posttransplant management were developed and recommendations were produced using the Delphi technique involving a Panel of 14 experts. ATG/ATLG was strongly recommended as part of myeloablative conditioning regimen prior to matched or mismatched unrelated bone marrow or peripheral blood allogeneic HSCT in malignant diseases to prevent severe acute and chronic GvHD. ATG/ATLG was also recommended prior to HLA-identical sibling peripheral HSCT with good but lesser bulk of evidence. In reduced intensity or nonmyeloablative conditioning regimens, ATG/ATLG was deemed appropriate to reduce the incidence of acute and chronic GvHD, but a higher risk of relapse should be taken into account. Recommendations regarding dose, application, and premedication were also provided as well as post-transplant infectious prophylaxis and vaccination. Overall, these recommendations can be used for a proper and safe application of polyclonal ATG/ATLG to prevent GvHD after allogeneic HSCT.

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Impact of Thymoglobulin by Stem Cell Source (Peripheral Blood Stem Cell or Bone Marrow) After Myeloablative Stem Cell Transplantation From HLA 10/10-Matched Unrelated Donors

Abstract: Although our results confirm the recommendation for ATG to be added after PBSC transplantation, no obvious benefit was identified using this approach in the setting of BM transplantation. Only prospective studies may yield definitive answers to this question.

Cited by 13 publications

References 34 publications

Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival

Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival

HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation

Rabbit ATG/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel

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