Feasibility and Outcomes of a Third Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Few therapeutic options are available for patients with acute myeloid or lymphoblastic leukemia (AML/ALL) relapsing after a second allogeneic stem cell transplantation (alloSCT2). In selected patients a third allogeneic stem cell transplantation (alloSCT3) has been used, but no detailed analysis is available so far. The European Society for Blood and Marrow Transplantation (EBMT) registry was screened for patients with acute leukemia (AL) receiving alloSCT3 from an identical or alternative donor to treat AL in either haematological relapse or disease persistence after alloSCT2 between 2001 and 2018. Feasibility, efficacy, outcome, and risk factors of this approach were analyzed retrospectively. Forty-five patients (median age, 37 years, range 12–71) with AML (n=34) or ALL (n=11) were identified. Eleven patients received alloSCT3 in complete remission (CR), 34 had active disease. Fifteen patients were transplanted from the same donor at all three transplants, 30 patients had at least 2 different donors. Between alloSCT2 and alloSCT3, the donor was changed in 25 patients. After alloSCT3, 38 patients engrafted, and 26 achieved CR or CR with incomplete hematological reconstitution (CRi). Acute graft-versus-host disease (GvHD) grade II–IV was observed in 19%, chronic GvHD occurred in 13%. After 1-year, cumulative incidences of leukemia relapse and non-relapse mortality were 47% and 42%, respectively. Median progression free and overall survival (PFS/OS) from alloSCT3 were 2.5 and 4 months, respectively, 1-year PFS and OS were 11% and 20%,. Outcome was improved in patients with at least one donor change (1-year PFS/OS: 17%/30%), further factors for better outcome included an unrelated donor for alloSCT3, Karnofsky performance score >80, and more recent year of alloSCT3. Only patients with AML achieved >1 year OS. In conclusion, results after a third alloSCT are poor, limiting this procedure to few, highly selected patients. Recurrent relapses of acute leukemia after alloSCT remain an unmet therapeutic need.