title: Graft-versus-Host Disease Prophylaxis in Unrelated Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil.
abstract: Clinical efficacy of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has been demonstrated in haploidentical and HLA-matched bone marrow but not in unrelated peripheral blood stem cell (PBSC) transplantations. Also, no direct comparisons have been published with current standard of care, combination of antithymocyte globulin (ATG), calcineurin inhibitors, and either methotrexate or mycophenolate mofetil (MMF). Eighty-six adult patients (median age 34 years; range, 18 to 59) with acute myeloblastic and lymphoblastic leukemia underwent unrelated PBSC transplantation with PTCy, tacrolimus, and MMF as GVHD prophylaxis in the single-center trial (clinicaltrial.govNCT02294552). The control group comprised 125 consecutive historical control patients who received ATG, tacrolimus, and methotrexate or MMF. Cumulative incidences of grades II to IV acute (19% versus 45%, P = .0003), grades III to IV acute (4% versus 27%, P < .0001), and chronic GVHD (16% versus 65%, P < .0001) were significantly lower in the PTCy compared with the ATG group. PTCy-based prophylaxis was associated with reduced incidence of nonrelapse mortality (16% versus 36%, P = .005; HR, .55; 95% CI, .34 to .89) and improved overall survival (69% versus 40%, P = .0007; HR, .43; 95% CI, .26 to .70), event-free survival (65% versus 38%, P = .0006; HR, .49; 95% CI, .31 to .78), and GVHD relapse-free survival (52% versus 12%, P < .0001). PTCy-based prophylaxis also had a better safety profile compared with ATG with reduced incidence of veno-occlusive disease, cytomegalovirus reactivation, invasive mycosis, and reduced severity of mucositis. In this study we demonstrated that PTCy in combination with tacrolimus and MMF is a safe and effective GVHD prophylaxis for unrelated PBSC transplantation. Although there are several limitations of the historical control approach, this study suggests the superiority of a PTCy-based approach over an ATG-based prophylaxis.
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation. Electronic address: moisiv@mail.ru.
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Moiseev
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Pirogova
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Alexandr L
authors.initials: AL
authors.lastname: Alyanski
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Babenko
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Tatyana L
authors.initials: TL
authors.lastname: Gindina
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Darskaya
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Slesarchuk
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Bondarenko
authors.affiliation: R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, The First Saint-Petersburg State Medical University named I.P. Pavlov, Saint-Petersburg, Russian Federation.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Afanasyev
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000628:therapy*; D011292:Premedication / Q000379:methods* / Q000401:mortality; D016559:Tacrolimus / Q000627:therapeutic use; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Antithymocyte globulin; Graft-versus-host disease; Post-transplantation cyclophosphamide; Unrelated HCT