Lower dose of antithymocyte globulin does not increase graft-versus-host disease in patients undergoing reduced-intensity conditioning allogeneic hematopoietic stem cell transplant

Salem, G; Ruppert, Amy S.; Elder, Patrick; Hofmeister, Craig C.; Benson, Don M.; Penza, Sam; Andritsos, Leslie A.; Klisovic, Rebecca B.; Vasu, Sumithira; Blum, William; Devine, Steven M.; Jaglowski, Samantha; Efebera, Yvonne A.

doi:10.3109/10428194.2014.956314

Cited by 13 publications

(10 citation statements)

References 25 publications

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“…17,18 Although the three different protocols used different doses of ATG (15-60 mg/kg), it would appear that there was no significant difference between the various doses, as has been shown previously. 19 Interestingly, in our study, the use of ATG was not found to correlate with a lower incidence of chronic GvHD and was not associated with a higher relapse rate.…”

Section: Discussioncontrasting

confidence: 56%

Sequential therapy for patients with primary refractory acute myeloid leukemia: a historical prospective analysis of the German and Israeli experience

et al. 2019

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Primary refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The FLAMSA-reduced intensity conditioning protocol (total body irradiation or treosulfan-based) has been described as an effective approach in patients with refractory leukemia undergoing allogeneic hematopoietic cell transplantation. A modified protocol (without amsacrine) has also recently been used. We retrospectively analyzed the transplantation characteristics and outcomes of all consecutive patients between the years 2003 and 2017 (n=51) diagnosed with primary refractory AML who underwent transplantation at the University of Cologne and the Tel Aviv Medical Center. Median age was 54 years and median follow up was 37 months. Median time to neutrophil and platelet engraftment was 13 (range, 8-19) and 13 (range, 7-30) days, respectively. None of the patients had primary graft failure. Incidences of grade 2-4 and grade 3-4 acute graft-v ersus -host disease (GvHD), overall and moderate-severe chronic GvHD were 50% (95%CI: 41-67%), 12% (95%CI: 3-25%), 61% (95%CI: 47-72%), and 42% (95%CI: 34-51%), respectively. Anti-thymocyte globulin administration was associated with lower incidence of acute GvHD (HR: 0.327; P =0.02). Non-relapse mortality at three months and three years were 6% and 16%, respectively. Relapse incidences were 6% and 29%, respectively. Overall survival rates at three months, three and five years were 90%, 61%, and 53%, respectively. Chronic GvHD disease was associated with a decreased mortality rate (HR: 0.397; P =0.045). We conclude that sequential therapy in patients with primary refractory acute myeloid leukemia is safe and provides a remarkable anti-leukemic effect with durable survival and should be considered for every patient with primary refractory disease.

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Section: Discussioncontrasting

confidence: 56%

Sequential therapy for patients with primary refractory acute myeloid leukemia: a historical prospective analysis of the German and Israeli experience

et al. 2019

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“…Adding antithymocyte globulin (ATG) in 1 of its 3 commercially available preparations (Thymoglobulin [Genzyme, Cambridge, MA], ATGAM [Pharmacia, Piscataway, NJ], and ATG-Fresenius [ATG-F, Fresenius, Germany]) for in vivo T cell depletion has been shown to decrease the incidence of aGVHD and cGVHD, with mixed effects on disease relapse [4,[9][10][11][12][13][14]. These studies have used different preparations and dose intensities of ATG, making it difficult to compare outcomes between them [14].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Two Doses of Antithymocyte Globulin in Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation

Issa

Sharma

Zhao

et al. 2019

Biology of Blood and Marrow Transplantation

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The appropriate dose of antithymocyte globulin (ATG) to be used in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is yet to be determined. We retrospectively analyzed the outcomes of patients who underwent unrelated or mismatch related RIC allo-HSCT for hematologic malignancies and received r-ATG (4.5 mg/kg, 141 patients) versus R-ATG (6 mg/kg, 216 patients). There was a higher incidence of cytomegalovirus (P < .001) and Epstein-Barr virus viremia (P =.03) in the R-ATG group than in the r-ATG group. The cumulative incidences of acute graft-versus-host disease (aGVHD) grades II to IV at day 180 in the r-ATG and R-ATG groups were 59% and 44% (P = .006) and grades III to IV 20% and 12% (P = .029), respectively. In multivariable models adjusting for disease diagnosis, the risk of aGVHD grades III to IV did not reach statistical significance (P = .087). The respective cumulative incidences of chronic GVHD in the r-ATG and R-ATG groups were 26% and 15% (P = .10), respectively. There were no significant differences in relapse rate (P = .24), nonrelapse mortality (P = .96), progression-free survival (P = .24), overall survival (P = .70), and GVHD-free relapse-free survival (P = .24). In this retrospective analysis, aGVHD incidence was higher in those treated with r-ATG compared with R-ATG, but this did not translate into significant differences of clinical outcome. Given the increasing use of RIC allo-HSCT for treating malignant hematologic conditions, the correct dose and schedule of ATG administration should be defined by prospective randomized controlled trials.

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“…Although high-dose ATG (Thymoglobulin) was shown to reduce the risk of GVHD, it was also associated with increased infectious complications and nonrelapse mortality [10,11]. Subsequent studies demonstrated that ATG (Thymoglobulin) dose reductions to 6 to 8 mg/kg [12][13][14] decreased infectious complications, whereas a further reduction to 2 to 5 mg/kg is associated with a higher risk of GVHD [15,16]. The optimal ATG dosing strategy remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Optimizing Antithymocyte Globulin Dosing for Unrelated Donor Allogeneic Hematopoietic Cell Transplantation Based on Recipient Absolute Lymphocyte Count

Kennedy

Chen

Savani

et al. 2018

Biology of Blood and Marrow Transplantation

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Antithymocyte globulin (ATG) is used as prophylaxis against graft-versus-host disease (GVHD). Current dosing regimens for ATG are empiric and weight-based, and do not account for patient-specific factors. Furthermore, the target of ATG, recipient T cells post-cytotoxic chemotherapy, is not a function of recipient weight. We hypothesized the recipient peripheral blood absolute lymphocyte count (ALC) on the day of ATG administration would interact with the dose of ATG administered to predict transplantation outcomes. We retrospectively analyzed 135 patients who received ATG for GVHD prophylaxis for unrelated allogeneic hematopoietic cell transplantation at 3 different doses: 10 mg/kg, 7.5 mg/kg, and 5 mg/kg. There was no difference in 2-year overall survival (OS) among ATG dosing groups; however, deaths from infectious complications were significantly higher with higher doses of ATG (3.7% versus 19% versus 26.7%; P = .02). Severity of chronic GVHD was lower with higher doses of ATG (28% versus 24% versus 4%; P = .03). In multivariate analysis, the median peripheral blood ALC on day of ATG administration and the total amount of ATG interacted to predict OS (hazard ratio, .09; P = .03). For low recipient ALC (10th percentile, or .56 × 10/µL), a higher total ATG dose was associated with a greater risk of death, whereas for high recipient ALC (90th percentile, or 24.96 × 10/µL), a higher ATG dose was associated with a lower risk of death. Our findings suggest that the interaction between ATG and its target, the recipient lymphocyte, could represent a new paradigm for ATG dosing.

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Lower dose of antithymocyte globulin does not increase graft-versus-host disease in patients undergoing reduced-intensity conditioning allogeneic hematopoietic stem cell transplant

Cited by 13 publications

References 25 publications

Sequential therapy for patients with primary refractory acute myeloid leukemia: a historical prospective analysis of the German and Israeli experience

Sequential therapy for patients with primary refractory acute myeloid leukemia: a historical prospective analysis of the German and Israeli experience

Comparison of Two Doses of Antithymocyte Globulin in Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation

Optimizing Antithymocyte Globulin Dosing for Unrelated Donor Allogeneic Hematopoietic Cell Transplantation Based on Recipient Absolute Lymphocyte Count

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