Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) with FBA/FBAA Regimen Based Reduced-Intensity Conditioning: A Multicenter Clinical Trial in China

Abstract 1953

Reduced-intensity conditioning (RIC) regimens have emerged as an attractive modality to decrease transplant-related mortality (TRM). However, the potential higher relapse rate and graft rejection after RIC allogeneic hematopoietic stem cell transplant (allo-HSCT) are still under considerable debate. To further optimize the outcome of RIC allo-HSCT, we designed a novel RIC regimen called FBA/FBAA. Fludarabine (Flu) and cytosine arabinoside (Ara-C) have a synergistic effect on leukemia cells and regimens such as FLAG (Flu+Ara-C+G-CSF) have been proven to be effective in the treatment of acute myeloid leukemia (AML). The nonmyeloablative regimen comprising Flu and busulfan (Bu) has been demonstrated to have favorable effects on engraftment, overall survival (OS) and disease-free survival (DFS). Therefore, we assume that the combination of Flu, Bu and Ara-C as a novel RIC regimen for allo-HSCT would further enhance the transplant efficacy for AML patients. We reporthere 69 AML patients enrolled in the study from March 2007 to July 2011, among which 69 AML patients treated with allo-HSCT from HLA identical siblings (35/69, 50.72%) or unrelated donors (34/69, 49.28%). There were 38 male and 31 female patients with median age of 33 years (range:14□'61). At the time of conditioning, 60 patients were in CR1 (1 AML-M₁, 11 M₂, 24 M₄, 22 M₅, 2 M₆) and 9 in CR2 (3 M₂, 1 M₄, 5 M₅). HLA typing was performed with high-resolution technology. Amongst 66 patients, 50 had donors matched for HLA-A, -B and -DRB₁ alleles, while 16 had 1/2 allele mismatched donor. In the sibling donor group, the patients received Flu 30 mg/m²x5d, Bu 0.8 mg/kg q6h×3d and Ara-C 1.5g/m²×5d (FBA). In the unrelated donor group, ATG-Fresenius 5 mg/kg×4d was combined with FBA conditioning (FBAA). GVHD prophylaxis consisted of mycophenolate mofetil, cyclosporin and methotrexate. The median dose of mononuclear cells infused was 6.04 ×10⁸/kg (0.8∼20.1×10⁸/kg), with 4.91 (0.3□18.0) ×10⁶ CD34⁺ cells/kg. All patients successfully achieved hematopoietic reconstitution. The median time to engraftment of neutrophils >0.5×10⁹/L and platelet >20×10⁹/L were 13.07 (1.0∼22.0) days and 14.08 (0.0∼30.0) days post- transplantation, respectively. The chimeric status measured by short tandom repeat (STR)-PCR showed that the complete chimeras and mix-chimeras at day +30 and day +90 were 92.75%, 7.25% and 94.20%, 5.80% respectively. No graft rejection occurred. During the median follow-up of 24.6 months (0.8∼51.6 months), 16 patients (23.19%) developed acute GVHD (aGVHD grade II□F9 patients, grade III∼IV: 3 patients. Chronic GVHD (cGVHD) occurred in 26 of 67 patients who survived more than 3 months, with only 9 extensive types. During the follow-up period, death patients were 19, 9 patients died of non-relapse causes, 8 died from pneumonia. The probability of OS at +100 days, 1 year and 2-years were 97.10%, 81.84% and 75.07%, respectively, while the probability of DFS were 97.10%, 80.27% and 73.62%, respectively. The OS at 1 year and 2-years for related and unrelated donor groups were 83.40%, 80.52% and 83.40%, 66.74% (P=0.263), respectively, and the DFS were 83.40%, 77.42% and 83.40%, 64.18% (P=0.431). In conclusion, these interim results demonstrate that the FBA/FBAA regimen is a safe and effective conditioning regimen for allo-HSCT for AML patients, with effective engraftment, low incidence of graft rejection and relapse as well as decreased incidence of severe aGVHD and cGVHD. The trial comparing this regimen with standard Bu-Cy +/− ATG are ongoing.