Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO)

Abstract

One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n ‫؍‬ 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n ‫؍‬ 29) ; (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n ‫؍‬ 28) versus 15 mg/kg rabbit ATG (n ‫؍‬ 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P ‫؍‬ .8) in the first and in 50% versus 11% (P ‫؍‬ .001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P ‫؍‬ .02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%; P ‫؍‬ .04), as confirmed by multivariate analysis (P ‫؍‬ .03). Time to 50 ؋ 10 9 /L platelets was comparable in the first trial (21 vs 24 days; P ‫؍‬ .3) and delayed in the ATG arm in the second trial (23 vs 38 days; P ‫؍‬ .02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG. (Blood. 2001;98:2942-2947)

Impact of rabbit ATG-containing myeloablative conditioning regimens on the outcome of patients undergoing unrelated single-unit cord blood transplantation for hematological malignancies

“…In fact, it is because of ATG's beneficial effects in cases of HLA disparities that ATG has been recommended. 11,22,28 Although we acknowledge the limitations of our retrospective study based on a relatively small number of mostly young patients, our results suggest that the use of ATG during myeloablative conditioning of patients receiving single-unit allo-CBT should be handled cautiously outside the clinical trial setting. From our study, no conclusions can be drawn with certainty concerning patients who received nonmyeloablative conditioning and those transplanted with double-unit cord blood or with in vitro expanded cord blood.…”

“…9 One of the strategies developed to reduce the risk of graft rejection has been to provide for in vivo recipient T-cell depletion in blood and lymphoid tissues by using antithymocyte globulin (ATG), a set of polyclonal antibodies directed against a wide range of immune cell epitopes. 10,11 However, ATG use in combination with a conditioning regimen before allo-SCT is still controversial, especially for patients receiving a myeloablative single-unit cord blood transplantation (allo-CBT). 12 The aim of this multicenter retrospective study was to assess the impact of ATG on the outcome of 91 consecutive patients who underwent a single-unit allo-CBT following a myeloablative conditioning regimen at three French transplant centers.…”

Reduced-intensity conditioned allogeneic haematopoietic stem cell transplantation results in durable disease-free and overall survival in patients with poor prognosis myeloid and lymphoid malignancies: eighty-month follow-up

“…In unrelated donor transplants, the use of ATG for in vivo T-cell depletion was found to be useful by some but not by others 25,26 Bacigalupo et al 27 reported a randomized prospective study of the use of ATG in unrelated donor marrow transplantation and found that though the risk of grade III-IV acute GVHD is markedly reduced in the ATG cohort, this does not result in the reduction of treatment-related mortality because of an increased risk of infections. They also noted that though the survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.…”

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

“…The benefit of anti-thymocyte globulin (ATG) for the prevention of acute and chronic GVHD has been proven in randomized studies [54][55][56][57]. A meta-analysis of six randomized, controlled trials demonstrated that the incidences of grade II-IV and grade III-IV acute GVHD and extensive chronic GVHD were significantly lower in patients who received ATG [58].…”