Post-Transplantation Cyclophosphamide: From Pharmacological Principles to Clinical Practice

Despite a considerable increase in the number of bone marrow donor registries, only 16–75 % of patients potentially have a fully matched unrelated donor, and an HLA-matched donor is not easy to find even among family members. Historically, the use of partially HLA-matched related (haploidentical) donors have been limited due to the high incidence of graft-versus-host disease (GvHD), high non-relapse mortality, and low overall survival rates. Efforts to improve the results of haploidentical transplantation were aimed at the depletion of graft T-cells. Although the ex vivo T-cell depletion virtually eliminates the possibility of GvHD, such allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with a high relapse risk and high mortality from infectious complications. To selectively deplete T-cells, a GvHD prevention method was elaborated, which uses high doses of cyclophosphamide (post-transplantation cyclophosphamide, PTCy). The administration of PTCy on Day +3 and Day +4 after transplantation results in elimination of alloreactive T-cells, which considerably reduces the incidence of acute and chronic GvHD and improves antitumor control. This method allowed to overcome the HLA barrier and to achieve survival rates after haplo-HSCT similar to those after HLA-matched transplantation. This review also addresses the pharmacological basis of biological effects of PTCy and analyzes the key clinical findings on the use of PTCy in allo-HSCT.

• Anna Aleksandrovna Kravtsova National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0009-0003-8861-9106 (unauthenticated)
• M.Yu. Drokov National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0001-9431-8316 (unauthenticated)

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