Impact of T‐cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party

Samarasinghe, Sujith; Clesham, Katherine; Iacobelli, Simona; Sbianchi, Giulia; Knol, Cora; Hamladji, Rose‐Marie; Socié, Gèrard; Aljurf, Mahmoud; Koh, Mickey; Sengeloev, Henrik; Dalle, Jean‐Hugues; Robinson, Stephen; Lint, Maria Teresa Van; Halkes, Constantijn J.M.; Beelen, Dietrich; Mufti, Ghulam J.; Snowden, John A.; Blaise, Didier; Tour, Régis Peffault de la; Marsh, Judith; Dufour, Carlo; Risitano, Antonio M.

doi:10.1002/ajh.25314

Cited by 21 publications

(17 citation statements)

References 23 publications

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“…Although not yet confirmed in the context of RCTs, which failed in the past to demonstrate an advantage using ATG [39], a recent report from the EBMT Severe Aplastic Anemia Working Party, with large numbers of patients, confirms the beneficial role of in vivo T-cell depletion with ATG or Alemtuzumab, which was associated with a significant survival benefit [40,41].…”

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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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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“…There is only one report from the EBMT Severe Aplastic Anemia (SAA) Working Party, with large numbers of patients, which states the beneficial role of in vivo T-cell depletion with ATG or Alemtuzumab with a significant survival benefit, but they conclude that alemtuzumab reduced the risk of acute and chronic GVHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA. 17 There is not any recommended dose for ATG/ATLG in their report. In the pediatric setting, there is no large prospective or retrospective randomized multicenter study on the optimal dose of ATLG in MUD HSCT of nonmalignant diseases.…”

Section: Resultsmentioning

confidence: 94%

Comparison of different doses of anti-human T-lymphocyte immunoglobulin for graft versus host disease prophylaxis in pediatric unrelated hematopoietic stem cell transplantation

Atay¹,

Akçay²,

Yenigürbüz³

et al. 2020

Preprint

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Background: Graft versus host disease is a major cause of morbidity and mortality after allogeneic HSCT from unrelated donors. ATLG is commonly used as prophylaxis for GVHD. The studies according to optimum dose of ATLG especially in pediatric patients are limited. Patients and Methods: Outcomes of 158 pediatric patients, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2) and 30 mg/kg (group 3) were analyzed retrospectively. The median duration of follow-up was 25.25 months (range, 1.1-79.5 months). Results: The incidences of acute and chronic GVHD were statistically not different between three groups (p=0.55 and p=0.45). But TRM at day 100 and OS at the end of follow-up was found significant inferior in patients received ATLG 10 mg/kg (p=0.006, p=0.004). Cox regression analysis showed that ATLG dose of 10 mg/kg (hazard ratio [HR] 0.500 [95% CI 0.301-0.829]; p=0.007), severe acute GVHD (HR 5.512 [2.027-14.993]; p=0.001), and having viral infection (HR 2.510 [1.034-6.089]; p=0.042) were significant prognostic factors for inferior OS. Conclusion: Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection; TRM and OS were superior in ATLG doses [?]20 mg/kg with no difference between 20 mg/kg and 30 mg/kg. So, it could be better to choose ATLG dose of 20 mg/kg in conditioning regimen for MUD HSCT in pediatric patients, but these observations should be supported with other multicenter prospective studies including larger patient population. Comparison of different doses of anti-human T-lymphocyte immunoglobulin for graft versus host disease prophylaxis in pediatric unrelated hematopoietic stem cell transplantation

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“…Comparing ATG with alemtuzumab, the latter was associated with a lower risk of both acute and chronic GVHD [16].…”

Section: Alemtuzumab-based (Fcc) Conditioning In Hsct For Saa: An Irrmentioning

confidence: 95%

“…(2) better conditioning regimens with the use of fludarabine, reduced cyclophosphamide doses, and avoidance of highdose total body or total lymphoid irradiation; (3) the introduction of CSA as postgrafting immunosuppression not only to reduce GVHD, but also to aid engraftment; and (4) in vivo T cell depletion with ATG or alemtuzumab [13][14][15][16][17] and avoidance of peripheral blood stem cells (PBSCs) as a stem cell source when using ATG-based conditioning [18,19]. There also have been major improvements in supportive care over time, including treatment of infections, especially invasive fungal disease [20], and improved access to and quality of blood products, including HLA-matched platelet transfusions for HLA-alloimmunized patients [21] (Figure 1).…”

Section: Current Indication For Hla-matched Unrelated Donor Hematopoimentioning

confidence: 99%

The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia

Marsh

Risitano

Mufti

2019

Biology of Blood and Marrow Transplantation

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The improved success of HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA) in recent decades has had an impact on the indications for and timing of this treatment modality. In the absence of a matched sibling donor (MSD), historically MUD HSCT was reserved as an option after failure to respond to at least 2 courses of immunosuppressive therapy (IST) in adults with SAA, but with improved outcomes over time, it is now considered following failure to respond to 1 course of IST. Recent national and international studies and guidelines now recommend upfront MUD HSCT as an option for children for whom an MUD is readily available, because outcomes are similar to those for MSD HSCT. Fludarabine-based conditioning and the use of in vivo T cell depletion with antithymocyte globulin or alemtuzumab has been associated with a reported overall survival (OS) of >85% in adult patients undergoing MUD HSCT. However, the recent introduction of eltrombopag for patients with SAA has transformed the treatment landscape, and there is currently much interest in its use with IST as upfront treatment, which showed a high response rate in an early-phase study. The risks of HSCT, especially graft-versus-host disease (GVHD), need to be carefully balanced against the concerns of IST, namely relapse and later clonal evolution to myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). In the absence of a current prospective randomized trial comparing these 2 approaches, in this review we examine the evidence supporting consideration of early MUD HSCT in adults with SAA who would have been considered for MSD HSCT but who lack a MSD and for whom an MUD is readily available, especially using an irradiation-free conditioning regimen, with a low risk of GVHD, as another treatment option. This option may be offered to patients to provide them with an informed choice, with the aim of curing disease rather than achieving freedom from disease, relapse-free survival, or OS. Furthermore, understanding the immune signature for the response to IST and the immunologic responses to somatic mutations and clonal progression to MDS/AML may help define the future indications for upfront HSCT and a more precise medical approach to therapy.

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Impact of T‐cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party

Cited by 21 publications

References 23 publications

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

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

Comparison of different doses of anti-human T-lymphocyte immunoglobulin for graft versus host disease prophylaxis in pediatric unrelated hematopoietic stem cell transplantation

The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia

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