Haploidentical bone marrow transplants for hematological malignancies using non-myeloablative conditioning therapy and post-transplant immunosuppression with cyclophosphamide: results from a single Australian centre

Abstract

Background: HLA haploidentical bone marrow transplantation is a treatment option in patients with hematological malignancies who have no available HLA matched donor, but is limited by conditioning regimen toxicity, graft failure, relapse and graft versus host disease. Aims: To demonstrate safety and efficacy of haploidentical bone marrow transplantation with nonmyeloablative conditioning and high-dose post-transplant cyclophosphamide in adult patients with leukaemia or lymphoma. Methods: 12 patients, median age of 51 years, underwent transplantation with T cell replete bone marrow from a haplotype matched relative. The conditioning regimen consisted of cyclophosphamide, fludarabine, and low-dose TBI. Post-transplant immunosuppression consisted of a single dose of cyclophosphamide 50 mg/kg on day 3, followed by oral tacrolimus and mycophenolate mofetil. Outcomes reported are overall survival, engraftment and chimerism, toxicity, and clinical outcome. Results: All patients had neutrophil recovery (median 14.5 days), and 11 of 12 had platelet engraftment (median 17 days). Two patients had autologous reconstitution. Seven of 9 assessable patients had complete donor chimerism. Four patients had grade II-III GvHD, and none had grade IV GvHD. Four patientsdeveloped limited stage chronic GvHD. Five patients with AML relapsed. Two patients died of non-relapse causes, both from other malignancies, and 5 patients remain alive and relapse free. Median overall survival was 324 days (range 88-1163). Conclusion: This regimen is feasible and well-tolerated in older patients with high risk leukemia or lymphoma, with minimal short-term toxicity, and low rates of GVHD. The proportion of disease-free survivors indicates a graft versus malignancy effect is present in survivors. Keywords: hematological malignancy, bone marrow transplant, haploidentical, post-transplant cyclophosphamide