Post-Transplantation Cyclophosphamide after Bone Marrow Transplantation Is Not Associated with an Increased Risk of Donor-Derived Malignancy

Abstract

Post-transplant cyclophosphamide (PTCy) can be used for graft versus host disease (GVHD) prophylaxis alone or in combination with other agents and is associated with excellent rates of engraftment, acute and chronic GVHD, and an absence of post-transplant lymphoproliferative disease. No study has previously evaluated the risk for developing donor derived malignancy (DDM) in patients who receive PTCy. Giving chemotherapy in the immediate post-transplant period carries with it a theoretic risk of disturbing the graft at a time of increased hematopoietic stress and causing or accelerating the development of malignancy. From 2000-2011, 789 patients underwent allogeneic transplant and received PTCy at the Johns Hopkins Hospital. There were four cases of DDM identified among this large population, which is similar to or below the rate of DDM published in the literature. We found that the estimated cumulative incidence by competing risk analysis of DDM is 1.4% (standard error=1.02%). The use of PTCy does not appear to increase the risk of DDM.

Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial

“…(11) PTCy results in low rates of graft-versus host disease, (12)(13)(14)(15) post-BMT lymphoproliferative disorder, (16) and donor derived malignancies. (17) However, despite cures in the majority of patients and low toxicity, the graft failure rate, albeit all with full host recovery, was 50% (one patient suffered secondary graft failure after the manuscript was published). In an attempt to decrease graft failure, we hypothesized that increasing the dose of total body irradiation (TBI) from 200 to 400 cGy before BMT would increase engraftment without increasing transplant-related morbidity and mortality.…”

Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203)

“…The mechanism of action suggests an upregulation of T-reg lymphocytes (18). Moreover, PTCy has been associated with very low rates of post-transplant lymphoproliferative disorder (29), donor derived leukemia (30), and a low immunosuppressive burden after BMT (31). This approach has consistently been associated with low rates of grades III-IV acute GVHD and chronic GVHD.…”

Haploidentical hematopoietic cell transplantation for adult acute myeloid leukemia: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…While there has been questioning of donor-derived malignancies (DDM) associated with PTCy, a recent retrospective study by the Hopkins group showed an extremely low proportion of patients with a DDM (4 out of 789) over a 10-year period, suggesting that PTCy does not appear to increase the risk of DDM. 108 However, the authors acknowledge the short follow-up period of their study and report the need for continued close monitoring of DDMs over a longer follow-up time.…”