Sequential intensified conditioning followed by prophylactic DLI could reduce relapse of refractory acute leukemia after allo-HSCT

Abstract

The major obstacle is leukemia relapse for refractory leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously introduced a strategy of sequential intensified conditioning and early rapid immunosupressant withdrawal for refractory leukemia undergoing allo-HSCT, with 5-year overall survival (OS) and 3-year relapse rate of 44.6% and 33.3%. To reduce leukemia relapse, prophylactic donor lymphocyte infusion (DLI) was administered based on our historical strategy. A total of 153 refractory advanced acute leukemia patients were enrolled in this prospective study. According to the availability of donor lymphocytes and the criteria for DLI, 144 patients surviving day +60 were divided into two groups (80 DLI versus 64 non-DLI). The relapse rate was less and OS was better in patients receiving DLI than in those not receiving DLI (22.7% vs 33.9%, P=0.048; 58.1% vs 54.9%, P=0.043). The non-relapse mortality (NRM) was similar between DLI and non-DLI groups (P=0.104). Overall, the 5-year overall and disease-free survival post-transplantation were 51.1%±5.7% and 49.2%±5.3%. The 5-year relapse rate and NRM were 27.3%±4.4% and 29.7%±5.3%. Multivariate analysis revealed that lower bone marrow blasts on day 0, DLI and chronic graft-versus-host disease were associated with less relapse and better OS. The strategy of sequential intensified conditioning followed by early immunosupressant withdrawal and DLI could reduce relapse of refractory acute leukemia after allo-HSCT and improve survival.

Haploidentical versus HLA-matched sibling transplantation for refractory acute leukemia undergoing sequential intensified conditioning followed by DLI: an analysis from two prospective data

“…Recently, some studies showed that intensified conditioning followed by allo-HSCT could achieve acceptable outcomes for refractory leukemia [5][6][7][8][9]. In our transplant center, a strategy of sequential intensified conditioning followed by donor lymphocyte infusion (DLI) was implemented since 2009, and encouraging outcomes were reported previously [10].…”

“…Ciclosporin A (CsA) + methotrexate (MTX) were administered in patients undergoing MSD transplants for GVHD prophylaxis. CsA + MTX + antithymocyte globulin (ATG) and mycophenolate were used in patients receiving HID [10].The total dose of ATG (rabbit antihuman thymocyte immunoglobulin, ImtixSangstat, Lyon, France) was randomly assigned as 7.5 mg/kg from days − 3 to − 1 or 10.0 mg/kg from days − 4 to − 1 in one trial (NCT01883180), and just 10.0 mg/kg from days − 4 to − 1 for all patients in another trial (NCT02673008).…”

“…The prevention of leukemic relapse included early tapering of immunosuppressant, prophylactic, and preemptive therapies according to our previous literatures [10,22].…”

“…In this study, we analyzed data from two prospective multicenter trials, to investigate the transplant outcomes of HID versus MSD for refractory acute leukemia by using our transplant strategy of sequential intensified conditioning followed by DLI [10].…”

Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

“…Comparing the two groups (80 DLI versus 64 non-DLI), the relapse rate was less and OS was superior in patients receiving DLI than in those without DLI administration (22.7% vs. 33.9%, p = 0.048; 58.1% vs. 54.9%, p = 0.043). In a multivariate analysis, DLI and cGvHD were associated with less relapse and improved OS [68].…”