Reduced-Intensity Conditioning with FBA/FBAA Regimen Is Feasible for Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML): Interim Results of a Multicenter Clinical Trial in China.

Abstract 196

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 report here 52 AML patients treated with allo-HSCT from HLA identical siblings (26/52, 50%) and unrelated donors (26/52, 50%) enrolled from March 2007 to March 2009. There were 31 male and 21 female patients with median age of 33 years (range:14∼60). At the time of conditioning, 47 patients were in CR1 (1 AML-M₁, 8 M₂, 21 M₄, 15 M₅, 2 M₆) and 5 in CR2 (2 M₂, 3 M₅). HLA typing was performed with high-resolution technology. Amongst 52 patients, 42 had donors matched for HLA-A, -B and -DRB₁ alleles, while 10 had 1 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 5.95 ×10⁸/kg (0.77∼20.10×10⁸/kg), with 5.08 (0.29∼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 14.3 (8∼25) days and 16.5 (9∼30) days post- transplantation, respectively. The chimeric status measured by short tandom repeat (STR)-PCR showed that the complete chimeras at day +30 and day +90 were 86.1% and 92.1%, respectively. No graft rejection occurred. During the median follow-up of 9.1 months (1∼28 months), only 8 patients (15.4%) developed acute GVHD (aGVHD grade II: 7, grade III∼IV:1). Chronic GVHD (cGVHD) occurred in 23 of 48 patients (47.9%) who survived more than 3 months, with only 4 (8.3%) extensive type. 8 patients (15.4%) relapsed, and were treated with chemotherapy combined with infusion of frozen G-CSF mobilized donor peripheral blood stem cells or donor lymphocytes. 4 of these patients went into complete remission (1 relapsed after 3 months). During the follow-up period, a total of 9 (17.3%) deaths from transplant-related pneumonia (4, 7.7%) and relapsed disease (5, 9.6%) occurred. The probability of OS at +100 days, 1 year and 2-years were 100%, 78.0% and 73.9%, respectively, while the probability of DFS were 100%, 78.0% and 65.9%, respectively. The OS were 81.8% and 74.1% respectively at 1 year, 81.8% and 67.4% (P=0.352) respectively at 2 years for related and unrelated donor group. Similarly, the DFS were 81.8% and 74.1% respectively at 1 year, 71.5% and 60.6% (P=0.439) respectively at 2 years for related and unrelated donor group. 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. We await the complete analyses of the results and verification of the above results.