Improved Outcome of Refractory/Relapsed Acute Myeloid Leukemia after Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation with Myeloablative Conditioning and Early Prophylactic Granulocyte Colony-Stimulating Factor-Mobilized Donor Lymphocyte Infusions

Abstract

We carried out post-transplantation cyclophosphamide (PTCy)-based haploidentical peripheral blood stem cell transplantation in 51 patients with refractory/relapsed acute myeloid leukemia not in remission. The first 10 patients received nonmyeloablative conditioning followed by planned granulocyte colony-stimulating factor (G-CSF)-mobilized donor lymphocyte infusions (DLIs) on days 35, 60, and 90. No patient developed graft-versus-host disease (GVHD), but 90% had disease progression between 3 and 6 months. A subsequent 41 patients received myeloablative conditioning (MAC); the first 20 patients did not receive DLIs (MAC group) and the next 21 patients received G-CSF-mobilized DLIs (G-DLI) on days 21, 35, and 60 (MAC-DLI group). The incidence of disease progression and progression-free survival at 18 months were 66% and 25% in the MAC group compared with 21.4% and 61.9% in the MAC-DLI group (P = .01). Chronic GVHD but not acute GVHD was increased in the MAC-DLI group (41.2% versus 11%, P = .05). Natural killer cell alloreactive donor was associated with lower incidence of disease progression in the MAC but not in MAC-DLI group. The only factor favorably influencing disease progression and progression-free survival was administration of G-DLI after myeloablative conditioning. Our study shows that early administration of G-DLI is feasible after PTCy-based haploidentical hematopoietic stem cell transplantation for refractory/relapsed acute myeloid leukemia and might be associated with improved survival after MAC.

Keywords: AML; DLI; Haploidentical; Post-transplantation cyclophosphamide; Refractory.