- Nationwide Survey on the Use of Horse Antithymocyte Globulins (ATGAM) in Patients with Acquired Aplastic Anemia: A Report on Behalf of the French Reference Center for Aplastic Anemia. [Journal Article]
- AJAm J Hematol 2018 Jan 27
- Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG...
Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG for first-line treatment of severe AA. The French Health Agency (ANSM) permitted a patient-named Authorization for Temporary Use (ATU) program of hATG (ATGAM, Pfizer) in patients with AA in 2011 since commercial access to hATG is not approved. We took advantage of this program to analyze the outcomes of 465 patients who received ATGAM plus CSA as first line treatment (n=379; 81.5%), or for refractory (n=26) or relapsed disease (n=33), from September 2011 to March 2017. In the entire cohort one year, 72% of the patients had partial and 13% had complete response, with worse response for patients with severe AA and a longer interval between diagnosis and IST (more than 6 months). Severe adverse events were mainly linked to infections (24%), hemorrhages (6%) and elevated liver function tests (5%). Overall at 12 months, 9.7% of patients required second line IST and 15.6% received transplantation. Fifty-five patients died during the study mainly because of infections (53%). Factors predicting independently worse survival were age over 40 years, neutrophils less than 0.5x109 /L, male gender and longer delay between diagnosis and hATG (>6 months period). This study does illustrate the results of ATGAM with CSA in a true-life perspective and confirms ATGAM as standard of care IST to treat patients with AA not eligible for HSCT. This article is protected by copyright. All rights reserved.
- Long-term Nonhuman Primate Renal Allograft Survival Without Ongoing Immunosuppression in Recipients of Delayed Donor Bone Marrow Transplantation. [Journal Article]
- TTransplantation 2018 Jan 04
- CONCLUSIONS: This study provides proof of principle that induction of mixed chimerism and long-term renal allograft survival without immunosuppression after delayed donor bone marrow transplantation is possible with clinically available reagents.
- Usefulness of valacyclovir prophylaxis for cytomegalovirus infection after anti-thymocyte globulin as rejection therapy. [Journal Article]
- KJKorean J Intern Med 2017 Dec 15
- CONCLUSIONS: In conclusion, valacyclovir prophylaxis is effective in the prevention of CMV infection after ATG treatment for steroid resistant TCMR.
- Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation. [Randomized Controlled Trial]
- JCJ Clin Oncol 2017 Dec 20; 35(36):4003-4011
- Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-vers...
Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.
- Horse versus rabbit antithymocyte globulin in immunosuppressive therapy of treatment-naïve aplastic anemia: a systematic review and meta-analysis. [Review]
- AHAnn Hematol 2017; 96(12):2031-2043
- The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systemat...
The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.
- Reduced-toxicity alternate-donor stem cell transplantation with posttransplant cyclophosphamide for primary immunodeficiency disorders. [Journal Article]
- PBPediatr Blood Cancer 2018; 65(1)
- We describe here the outcomes of reduced-toxicity alternate-donor stem cell transplant (SCT) with posttransplant cyclophosphamide (PTCy) for primary immunodeficiency disorders (PIDs) in eight childre...
We describe here the outcomes of reduced-toxicity alternate-donor stem cell transplant (SCT) with posttransplant cyclophosphamide (PTCy) for primary immunodeficiency disorders (PIDs) in eight children (haploidentical-seven and matched unrelated donor-one). The conditioning was with serotherapy (alemtuzumab-3/rabbit-anti-thymoglobulin-5); fludarabine, cyclophosphamide, and total body irradiation-5 (additional thiotepa-3); fludarabine and treosulfan-2; and fludarabine and busulfan-1. All received PTCy 50 mg/kg on days 3 and 4 as graft versus host disease prophylaxis along with tacrolimus and mycophenolate. Mean CD34 dose was 13.8 × 106 /kg. Two children died because of PIDs. Acute graft versus host disease up to grades I and II was seen in three children. All six survivors are fully donor and disease free at median follow-up of 753 days. Alternate donor SCT with PTCy is feasible in PID and has good outcomes.
- Clinical outcomes in adult patients with aplastic anemia: A single institution experience. [Journal Article]
- AJAm J Hematol 2017; 92(12):1295-1302
- Newer treatment modalities are being investigated to improve upon historical outcomes with standard immunosuppressive therapy (IST) in aplastic anemia (AA). We analyzed outcomes of adult patients wit...
Newer treatment modalities are being investigated to improve upon historical outcomes with standard immunosuppressive therapy (IST) in aplastic anemia (AA). We analyzed outcomes of adult patients with AA treated with various combinatorial anti-thymoglobulin-based IST regimens in frontline and relapsed/refractory (R/R) settings. Pretreatment and on-treatment clinical characteristics were analyzed for relationships to response and outcome. Among 126 patients reviewed, 95 were treatment-naïve (TN) and 63, R/R (including 32 from the TN cohort); median ages were 49 and 50 years, respectively. Overall survival (OS) was superior in IST responders (P < .001). Partial response to IST was associated with shorter relapse-free survival (RFS), as compared with complete response (P = .03). By multivariate analysis, baseline platelet and lymphocyte count predicted for IST response at 3 and 6 months, respectively. While additional growth factor interventions led to faster count recovery, there were no statistically significant differences in RFS or OS across the various frontline IST regimens (i.e., with/without G-CSF or eltrombopag). While marrow cellularity did not correlate with peripheral-blood counts at 3 months, cytomorphological assessment revealed dyspoietic changes in all nonresponders with hypercellular-marrow indices. Covert dysplasia, identified through early bone marrow assessment, has implications on future therapy choices after IST failure. Salvage IST response depended upon prior response to ATG: prior responders (46%) vs. primary refractory (0%) (P < .01). In the R/R setting, there was no survival difference between IST and allogeneic stem cell transplant groups, with a trend toward superior OS in the former. Transplant benefits in the R/R setting may be underrealized due to transplant-related mortality.
- In-vivo or ex-vivo T cell depletion or both to prevent graft-versus-host disease after hematopoietic stem cell transplantation. [Review]
- EOExpert Opin Biol Ther 2017; 17(11):1401-1415
- Hematopoietic stem cell transplantation (HSCT) represents a widely accepted therapeutic strategy for the treatment of hematologic disorders which are otherwise considered incurable. Alloreactive T ce...
Hematopoietic stem cell transplantation (HSCT) represents a widely accepted therapeutic strategy for the treatment of hematologic disorders which are otherwise considered incurable. Alloreactive T cells infused with the stem cell inoculum may generate graft-versus-host disease (GVHD) representing one the most relevant obstacles to the successful outcome of patients receiving allogeneic HSCT. Areas covered: In this review, the authors provide an overview of the most recent approaches of T-cell depletion (TCD) including ex-vivo αβ+ TCD and in-vivo TCD with anti-thymocyte globulin (ATG). Expert opinion: Ex vivo depletion of donor T-cells prevents both acute and chronic GVHD without the need for any additional posttransplant immunological prophylaxis either in haploidentical HSCT and HLA matched transplants. Three prospective trials evaluating the efficacy of ATG in matched unrelated donor transplant recipients demonstrated that ATG reduces the incidence of both acute and chronic GVHD without a significant increase of relapse rate, and similar results have been reported in the setting of blood stem cell grafts from matched sibling donors.
- A French Cohort Study of Kidney Retransplantation after Post-Transplant Lymphoproliferative Disorders. [Journal Article]
- CJClin J Am Soc Nephrol 2017 Oct 06; 12(10):1663-1670
- CONCLUSIONS: The recurrence of post-transplant lymphoproliferative disorder among patients who underwent retransplantation in France is a rare event.
New Search Next
- Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia. [Multicenter Study]
- AHAnn Hematol 2017; 96(11):1907-1914
- Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit AT...
Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10(9)/L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10(9)/L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.