Prevention of Acute Graft-Versus-Host Reaction after Allogeneic Unrelated Hematopoietic Stem Cell Transplantation: Comparison of Effectiveness of Treatment Regimens Based on Anti-Thymocyte Globulin and Cyclophosphamide

OV Pirogova, IS Moiseev, EV Babenko, OA Slesarchuk, OV Paina, SN Bondarenko, EV Morozova, AL Alyanskii, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician IP Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Ol’ga Vladislavovna Pirogova, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)338-62-65; e-mail: dr.pirogova@gmail.com

For citation: Pirogova OV, Moiseev IS, Babenko EV, et al. Prevention of Acute Graft-Versus-Host Reaction after Allogeneic Unrelated Hematopoietic Stem Cell Transplantation: Comparison of Effectiveness of Treatment Regimens Based on Anti-Thymocyte Globulin and Cyclophosphamide. Clinical oncohematology. 2016;9(4):391–97 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-391-397


ABSTRACT

Background & Aims. So far there is no data presented on the effectiveness of prevention of the graft-versus-host reaction (GVH) using post-transplant cyclophosphamide (PTCy) prescribed after unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study is to evaluate the incidence of acute and chronic GVH, the transplantation-associated mortality rate, the event-free and overall survival rates, as well as the toxicity profile and the incidence of infectious complications in the study group using cyclophosphamide for GVH prevention; the other aim is to carry out a comparative analysis of the obtained results with the historical control group.

Methods. 110 adult patients were enrolled in a clinical study to evaluate the effectiveness of GVH prevention, using PTCy (No. NCT02294552). In order to prevent GVH, the study group (PTCy group) received cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF). The historical control group (ATG group) consisted of 160 patients prescribed with a GVH prevention regimen including anti-thymocyte globulin (ATG), calcineurin inhibitors, and methotrexate or MMF. Peripheral blood stem cells were used as a source of the transplant.

Results. The cumulative incidence of II–IV degree acute GVH (18.2 % vs. 40.4 %, respectively; < 0.0001), III–IV degree GVH (4.5 % vs. 22.5 %, respectively; < 0.0001), and chronic GVH (21.7 % vs. 40.6 %, respectively; < 0.0001) was significantly lower in the PTCy group than in the ATG group. Prevention of GVH based on PTCy was associated with the reduction in transplant-associated mortality (12.7 % vs. 33.7 %, respectively; = 0.003), increased overall survival (70.9 % vs. 44.4 %, respectively; < 0.001), event-free survival (68.2 % vs. 38.1 %, respectively; < 0.001) and GVH- and relapse-free survival rates (59.1 % vs. 16.3 %, respectively; = 0.001). Prevention of GVH using PTCy (as compared to ATG) was less toxic, accompanied by a reduction in the incidence veno-occlusive disease (2.7 % vs. 10.9 %, respectively; = 0.016), severe mucositis (69.5 % vs. 87.6 %, respectively; < 0.001), and invasive mycosis (7.2 % vs. 29 %, respectively; < 0.001).

Conclusion. A combination of cyclophosphamide with tacrolimus and MMF is an effective regimen for GVH prevention in patients after allo-HSCT from an unrelated donor.


Keywords: graft-versus-host reaction, GVH prevention, allo-HCST, cyclophosphamide, anti-thymocyte globulin.

Received: March 30, 2016

Accepted: May 4, 2016

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