No indication of increased infection rates using low‐dose alemtuzumab instead of anti‐thymocyte globulin as graft‐versus‐host disease prophylaxis before allogeneic stem cell transplantation

Neumann, Thomas; Schneidewind, Laila; Thiele, Thomas; Pink, Daniel; Schulze, Meike; Schmidt, Christian A.; Krüger, William

doi:10.1111/tid.12822

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…Some said that personalized ATG dosage for GVHD prophylaxis may improve outcomes after transplantation [13,14]. In recent years, low dose therapies of alemtuzumab (0.5 mg/kg) [8] and ATG (2-6 mg/kg) have been developing [15][16][17]. The dosage of ATG varied depending on the studies, and individual dosing was reported to improve reconstitution of CD4 T cell and optimal dosage may differ among races.…”

Section: Discussionmentioning

confidence: 99%

Comparison of alemtuzumab, anti-thymocyte globulin, and post-transplant cyclophosphamide for graft-versus-host disease and graft-versus-leukemia in murine models

Mashima

Fujiwara

et al. 2021

PLoS ONE

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Graft-versus-host disease is a major complication after allogeneic hematopoietic stem cell transplantation for hematological malignancies. Immunosuppressive drugs, such as anti-thymocyte globulin, alemtuzumab, and post-transplant cyclophosphamide, have been used to prevent graft-versus-host disease in HLA-mismatched haploidentical hematopoietic stem cell transplantation. Here, we investigated whether these drugs could ameliorate graft-versus-host disease without diminishing the graft-versus-leukemia effect by using a xenogeneic transplanted graft-versus-host disease/graft-versus-leukemia model. Anti-thymocyte globulin treatment diminished graft-versus-host disease symptoms, completely depleted the infiltration of inflammatory cells in the liver and intestine, and led to prolonged survival. By contrast, improvement after post-transplant cyclophosphamide treatment remained minimal. Alemtuzumab treatment modestly prolonged survival despite an apparent decrease of Tregs. In the graft-versus-leukemia model, 1.5 to 2.0 mg/kg of anti-thymocyte globulin and 0.6 to 0.9 mg/kg of alemtuzumab reduced graft-versus-host disease with minimal loss of graft-versus-leukemia effect. Mice treated with 400 mg/kg of post-transplant cyclophosphamide did not develop graft-versus-host disease or leukemia, but it was difficult to evaluate the graft-versus-leukemia effect due to the sensitivity of A20 cells to cyclophosphamide. Although the current settings provide narrow optimal therapeutic windows, further studies are warranted to maximize the benefits of each immunosuppressant.

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Section: Discussionmentioning

confidence: 99%

Comparison of alemtuzumab, anti-thymocyte globulin, and post-transplant cyclophosphamide for graft-versus-host disease and graft-versus-leukemia in murine models

Mashima

Fujiwara

et al. 2021

PLoS ONE

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“…Interestingly, the administration of alemtuzumab seems to be associated with a lower incidence of reactivation, most likely due to its anti-B-cell properties [29,34]. In a study comparing ATG and alemtuzumab, the prevalence of EBV reactivation was 100% vs 58%, respectively [4], although not confirmed in another study [35]. These recent data underscore that all T-depletion strategies may not equally influence the risk of EBV reactivation, depending on their impact on decreasing B cells (the EBV reservoir) and on depleting T cells, more particularly EBV-specific memory T cells present in the graft.…”

Section: Incidence Of Ebv-dnaemia After Allogeneic Hsctmentioning

confidence: 94%

Epstein–Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada

Ratiu,

Dufresne,

Thiant

et al. 2024

Current Oncology

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Epstein–Barr virus-related post-transplantation lymphoproliferative disorder (EBV-PTLD) is a serious complication following hematopoietic stem cell transplantation (HSCT). A pre-emptive strategy using rituximab, which aims to manage patients early at the time of EBV reactivation to avoid PTLD, has been recommended by the most recent ECIL-6 guidelines in 2016. However, there is still a great heterogeneity of viral-load monitoring protocols, targeted patient populations, and pre-emptive treatment characteristics between centers, making precise EBV monitoring recommendations difficult. We conducted a literature review from the most recent publications between 1 January 2015 and 1 August 2023, to summarize the emerging data on EBV-PTLD prevention strategies in HSCT recipients, including the EBV-DNA threshold and use of rituximab. We also present the results of a survey of current practices carried out in 12 of the main HSCT centers across Canada. We confirm that pre-emptive rituximab remains an efficient strategy for EBV-PTLD prevention. However, there is an urgent need to perform prospective, randomized, multicentric trials with larger numbers of patients reflecting current practices to determine the best clinical conduct with regards to rituximab dosing, timing of treatment, and criteria to initiate treatments. Longer follow-ups will also be necessary to assess patients’ long-term outcomes.

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“…Several studies used multivariate analysis to examine the relationship between recipient sex and post-transplant active EBV infection [4,35,39,50,52,56,65,68,69,72,74,76,85,86,88,89,96,101] or PTLD [16,27,40,56,88,94,95,98]; none found a significant association. Three out of six studies [35,53,56,65,79,101] that analyzed the association between donor sex and post-HSCT active EBV infection showed a statistically significant association but in the opposite direction. In two studies, the risk for active EBV infection post-HSCT was higher in patients receiving a male donor transplant [53,56] while, in the other, patients receiving a female donor transplant appeared to be at greater risk [65].…”

Section: Other Risk Factorsmentioning

confidence: 98%

“…ATG use appears to be an important risk factor for the development of active posttransplant EBV infection or PTLD. Among 15 multivariate studies [4,41,45,46,51,53,56,66,68,69,74,79,85,86,96] that examined the association between ATG and active post-transplant EBV infection, 10 found a statistically significant association: Cesaro et al [41] (HR = 13.0 (95% CI: 2-96)), Fan et al [53] (OR = 7.69 (95% CI: 1.17-50.49)), Juvonen et al [66] (HR = 5.78 (95% CI: 2.47-13.5)), Liu et al [74] (HR = 14.081 (95% CI: 6.02-32.92)), Peric et al [85] (SHR = 4.9 (95% CI: 1.1-21.0)), Van Esser et al [96] (HR = 3.4 (95% CI: 1.6-1)), Gao et al [56] (HR = 6.3 (95% CI: 1.6-24.0)), Düver et al [51] (OR = 10.68 (95% CI: 1.15-98.86)), Ru et al [86] (HR = 4.29 (95% CI: 2.64-6.97)) and Kullberg-Lindh et al [68] (slope = 1.34; p = 0.004). All studies compared patients who received ATG versus those who did not, but one: Van Esser et al [96] reported the risk of EBV infection in patients receiving T-cell depleted (TCD) grafts with ATG versus patients receiving non-TCD grafts.…”

Section: Graft-versus-host Disease Prophylaxis/treatmentmentioning

confidence: 99%

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

et al. 2021

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This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.

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No indication of increased infection rates using low‐dose alemtuzumab instead of anti‐thymocyte globulin as graft‐versus‐host disease prophylaxis before allogeneic stem cell transplantation

Abstract: We saw no indication of increased infections rates when using low-dose alemtuzumab as GvHD prophylaxis before allogeneic stem cell transplantation in this retrospective analysis.

Cited by 6 publications

References 39 publications

Comparison of alemtuzumab, anti-thymocyte globulin, and post-transplant cyclophosphamide for graft-versus-host disease and graft-versus-leukemia in murine models

Comparison of alemtuzumab, anti-thymocyte globulin, and post-transplant cyclophosphamide for graft-versus-host disease and graft-versus-leukemia in murine models

Epstein–Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

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