BACKGROUND:Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown. METHODS: In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to received 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) of ATG. Analysis of disease-free survival, GVHD-free/recurrence-free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations. RESULTS:A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 28-1929 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-6 arm (14.3% vs 7.1%; P = .084). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for disease recurrence (12.8% vs 13.4%; P = .832) and nonrecurrence mortality (11.6% vs 17.0%; P = .263). The 5-year probability of disease-free survival was comparable between the groups (75.6% vs 69.6%; P = .283). The 5-year cumulative incidence of cGVHD was found to be higher with ATG-6 (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]) as well as that for late effects (71.2% vs 56.9%; P = .043). The 5-year probability of GRFS was higher in the ATG-10 group (41.0% vs 26.8%; P = .008). In the multivariate analysis, ATG-10 was found to be associated with a lower risk of cGVHD and improved GRFS. CONCLUSIONS: ATG-10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. Cancer 2017;123:2881-92.
RCT Entities:
BACKGROUND: Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown. METHODS: In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to received 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) of ATG. Analysis of disease-free survival, GVHD-free/recurrence-free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations. RESULTS: A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 28-1929 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-6 arm (14.3% vs 7.1%; P = .084). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for disease recurrence (12.8% vs 13.4%; P = .832) and nonrecurrence mortality (11.6% vs 17.0%; P = .263). The 5-year probability of disease-free survival was comparable between the groups (75.6% vs 69.6%; P = .283). The 5-year cumulative incidence of cGVHD was found to be higher with ATG-6 (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]) as well as that for late effects (71.2% vs 56.9%; P = .043). The 5-year probability of GRFS was higher in the ATG-10 group (41.0% vs 26.8%; P = .008). In the multivariate analysis, ATG-10 was found to be associated with a lower risk of cGVHD and improved GRFS. CONCLUSIONS:ATG-10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. Cancer 2017;123:2881-92.
Authors: Rosy Dabas; Kareem Jamani; Shahbal B Kangarloo; Poonam Dharmani-Khan; Tyler S Williamson; Samar Ousia; Caylib Durand; Don Morris; Douglas Mahoney; Lynn Savoie; Ahsan Chaudhry; Victor H Jimenez-Zepeda; Faisal M Khan; Andrew Daly; Jan Storek Journal: Blood Adv Date: 2019-05-14
Authors: Lisa V E Oostenbrink; Cornelia M Jol-van der Zijde; Katrine Kielsen; Anja M Jansen-Hoogendijk; Marianne Ifversen; Klaus G Müller; Arjan C Lankester; Astrid G S van Halteren; Robbert G M Bredius; Marco W Schilham; Maarten J D van Tol Journal: Front Immunol Date: 2019-03-06 Impact factor: 7.561
Authors: Arjun Datt Law; Maria Queralt Salas; Wilson Lam; Fotios V Michelis; Santhosh Thyagu; Dennis Dong Hwan Kim; Jeffrey Howard Lipton; Rajat Kumar; Hans Messner; Auro Viswabandya Journal: Biol Blood Marrow Transplant Date: 2018-08-07 Impact factor: 5.742