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

Ali, Maryan; Grønvold, B.; Remberger, Mats; Abrahamsen, Ingerid Weum; Myhre, Anne Grethe; Tjønnfjord, Geir E.; Fløisand, Yngvar; Gedde‐Dahl, Tobias

doi:10.1016/j.clml.2021.05.003

Cited by 6 publications

(17 citation statements)

References 45 publications

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“…The relapse rates were not significantly increased in most studies, ranging from 16-37%, with higher rates of relapse often linked to higher exposure of ATG ( 67 – 76 ). In most studies, infections were comparable between ATG treated patients and other GVHD prophylaxis strategies, with severe bacterial infections in 42-45% of patients reported (2 studies), invasive fungal disease in 14% (2 studies), and deaths to due to infections ranging from 15-17% of the total ( 67 – 76 ). Notably, the incidence of viral reactivations varied widely, from 7.5-62% of CMV reactivation, with the higher incidence exceeding the controls of this study ( 68 , 70 , 71 , 75 , 76 ).…”

Section: Anti-thymocyte Globulinmentioning

confidence: 85%

“…The median rates of grade II-IV aGVHD were 18% across the studies (ranging from 7-34%), and 28% cGVHD (16-28%) with 12% extensive cGVHD (6-13%), lower than controls in randomized studies ( 67 – 76 ). The relapse rates were not significantly increased in most studies, ranging from 16-37%, with higher rates of relapse often linked to higher exposure of ATG ( 67 – 76 ). In most studies, infections were comparable between ATG treated patients and other GVHD prophylaxis strategies, with severe bacterial infections in 42-45% of patients reported (2 studies), invasive fungal disease in 14% (2 studies), and deaths to due to infections ranging from 15-17% of the total ( 67 – 76 ).…”

Section: Anti-thymocyte Globulinmentioning

confidence: 93%

“…Studies have consistently shown reduction of acute and chronic GVHD after ATG exposure. Most studies are performed using peripheral blood, many randomized to controls, and most include matched related and unrelated donors ( 67 – 76 ). These studies represent over 1600 adult patients with hematologic malignancies treated with ATG, with the majority receiving ATG-F, with few receiving ATG-T.…”

Section: Anti-thymocyte Globulinmentioning

confidence: 99%

“…These studies represent over 1600 adult patients with hematologic malignancies treated with ATG, with the majority receiving ATG-F, with few receiving ATG-T. The median rates of grade II-IV aGVHD were 18% across the studies (ranging from 7-34%), and 28% cGVHD (16-28%) with 12% extensive cGVHD (6-13%), lower than controls in randomized studies ( 67 – 76 ). The relapse rates were not significantly increased in most studies, ranging from 16-37%, with higher rates of relapse often linked to higher exposure of ATG ( 67 – 76 ).…”

Section: Anti-thymocyte Globulinmentioning

confidence: 99%

“…In most studies, infections were comparable between ATG treated patients and other GVHD prophylaxis strategies, with severe bacterial infections in 42-45% of patients reported (2 studies), invasive fungal disease in 14% (2 studies), and deaths to due to infections ranging from 15-17% of the total ( 67 – 76 ). Notably, the incidence of viral reactivations varied widely, from 7.5-62% of CMV reactivation, with the higher incidence exceeding the controls of this study ( 68 , 70 , 71 , 75 , 76 ). In two studies, EBV reactivation was higher than controls, again ranging widely among studies, from 4-71% with the lower incidence possibly linked to the addition of CD20 blockade in the regimens ( 70 – 73 , 76 ).…”

Section: Anti-thymocyte Globulinmentioning

confidence: 99%

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Controversies and expectations for the prevention of GVHD: A biological and clinical perspective

Watkins

Williams

2022

Front. Immunol.

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Severe acute and chronic graft versus host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Historically, cord blood and matched sibling transplantation has been associated with the lowest rates of GVHD. Newer methods have modified the lymphocyte components to minimize alloimmunity, including: anti-thymocyte globulin, post-transplant cyclophosphamide, alpha/beta T cell depletion, and abatacept. These agents have shown promise in reducing severe GVHD, however, can be associated with increased risks of relapse, graft failure, infections, and delayed immune reconstitution. Nonetheless, these GVHD prophylaxis strategies have permitted expansion of donor sources, especially critical for those of non-Caucasian decent who previously lacked transplant options. This review will focus on the biologic mechanisms driving GVHD, the method by which each agent impacts these activated pathways, and the clinical consequences of these modern prophylaxis approaches. In addition, emerging novel targeted strategies will be described. These GVHD prophylaxis approaches have revolutionized our ability to increase access to transplant and have provided important insights into the biology of GVHD and immune reconstitution.

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Section: Anti-thymocyte Globulinmentioning

confidence: 85%

Section: Anti-thymocyte Globulinmentioning

confidence: 93%

Section: Anti-thymocyte Globulinmentioning

confidence: 99%

Section: Anti-thymocyte Globulinmentioning

confidence: 99%

Section: Anti-thymocyte Globulinmentioning

confidence: 99%

See 3 more Smart Citations

Controversies and expectations for the prevention of GVHD: A biological and clinical perspective

Watkins

Williams

2022

Front. Immunol.

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Allogeneic stem cell transplant recipients surviving at least 2 years without relapse: outcome and risk factors

Grønvold,

Ali,

Myklebust

et al. 2024

eJHaem

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Outcomes of 2‐year survivours undergoing allo‐haematopoietic stem cell transplantation at Oslo University Hospital were retrospectively assessed with the objectives of identification of risk factors for late death as possible means for precautionary measures and interventions to improve long‐term survival.421 patients with haematological malignancy, transplanted between 2005 and 2019, alive and free of disease after 2 years were included with data reported from The OUS‐HSCT registry. Median follow‐up was 6.2 years (2.016.1), and 232 patients (55%) were observed for minimum 5 years.The probability of being alive 5 and 10 years after HSCT was 86% and 76%. Primary risk factors for late death included initial diagnosis of age ≥ 60 years, chronic lymphocytic leukaemia (CLL), previous blood stream‐ or invasive fungal infection (BSI, IFI), and chronic graft‐versus‐host disease (cGVHD). Transplant‐related mortality (TRM) and relapse at 5 years were 9.0% and 7.7%, respectively. Two factors were associated with the latter: cytomegalovirus (CMV) seronegative donor and CLL. Compared with the age‐ and gender‐matched Norwegian general population, life expectancy was lower for each disease, except for CML.The prospect for the long‐term survival is good for 2‐year survivors of the allogeneic hematopoietic stem cell transplantation. However, life expectancy remains inferior to the age‐ and gender‐matched general population. Optimising prophylaxis and treatment for chronic GVHD, BSI and IFI are needed along with the improved adherence to guidelines for early detection of secondary malignancies. Measures to improve immune reconstitution, possibly the microbiota, and the use of CMV seropositive donors regardless of recipient sero‐status may be warranted and should be addressed in further studies.

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Epstein–Barr virus posttransplant lymphoproliferative disorder: update on management and outcomes

Lindsay

Othman

Heldman

et al. 2021

Current Opinion in Infectious Diseases

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Purpose of reviewManagement of Epstein-Barr virus posttransplant lymphoproliferative disorder (EBV PTLD) is complex, involving risk stratification, prevention and/or preemptive measures involving monitoring EBV DNAemia and balancing treatment options, using a combination of reduction of immune suppression, anti-B cell therapy, and cytotoxic T lymphocytes (CTLs). Recent findingsThe highest risk factor for the development of EBV PTLD in hematopoietic cell transplant (HCT) remains T cell depletion, with increasing use of antithymocyte globulin (ATG) or alemtuzumab in conditioning. In solid organ transplantation (SOT), the incidence of PTLD is highest among EBV seronegative recipients who are at risk for primary EBV infection following transplant in the first 12 months. Prevention is a critical component of the management of EBV PTLD. Although preemptive therapy remains standard of care, there continues to be heterogenicity and debate over the optimal choice of EBV DNA quantification and the threshold to use. Novel therapies such as donor-derived multipathogen and EBV specific CTLs for the prevention and third party CTLs for the treatment of EBV PTLD are promising, with rapidly expanding evidence, including large scale Phase III trials currently underway.

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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

Abstract: Addition of anti-thymocyte globulin in allogeneic stem cell transplantation with peripheral stem cells from matched unrelated donors improves graft-versushost disease and relapse free survival,

Cited by 6 publications

References 45 publications

Controversies and expectations for the prevention of GVHD: A biological and clinical perspective

Controversies and expectations for the prevention of GVHD: A biological and clinical perspective

Allogeneic stem cell transplant recipients surviving at least 2 years without relapse: outcome and risk factors

Epstein–Barr virus posttransplant lymphoproliferative disorder: update on management and outcomes

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