Allogeneic Stem Cell Transplantation for Core Binding Factor Alpha-Positive Adult Acute Myelogenous Leukemia with a Reduced Intensity Conditioning Regimen Consisting of Intravenous Busulfan, Fludarabine, and 400 cGy Total Body Irradiation

Translocation (8;21) in core binding factor alpha acute myelogenous leukemia (CBFA-AML) leads to the generation of the AML1-ETO fusion gene, which is generally associated with a favorable prognosis. Nevertheless, in line with recent reports based on mutation studies of the c-kit, FLT3, and Ras genes, we have also experienced poor clinical outcomes in some patients with CBFA-AML, with rapid relapse of patients within a few months of conventional intensive chemotherapy with cytosine arabinoside or even autologous stem cell transplantation (SCT) for patients in complete remission (CR). A few studies have used SCT as part of the therapeutic approach for CBFA-AML. To study the role of SCT, in light of the advances of transplant techniques, we performed a prospective study combining SCT with a novel reduced intensity conditioning (RIC) regimen. There were 10 men and 3 women with a median age of 42 years (range 17–50). Seven patients were categorized as CBFA-AML with additional cytogenetic abnormalities. Two patients had either FLT3-ITD or c-kit mutations. All CBFA-AML patients in CR received one cycle of consolidation chemotherapy before undergoing allogeneic SCT. Four patients had HLA-matched unrelated donors and the other donors were HLA-matched siblings. The preparative regimen comprised fludarabine 30 mg/m² on days–6 to –2, intravenous busulfan (Busulfex, Kirin-Brewery, Japan) 3.2 mg/kg/d on days–5 to –4, and fractionated total body irradiation (TBI) 200 cGy × 2 on day–1. Cyclosporine A (CsA) and a short course of standard dose methotrexate were used to prevent graft-versus-host disease (GvHD). If no acute GvHD occurred, the CsA was tapered over 4~8 weeks with the intent to discontinue by 3 to 5 months. All patients were engrafted successfully. Eleven patients are alive at a median follow-up of 12 months (range 3–18). Four (31%) out of 13 patients developed acute GvHD, and none were grade >II. Six patients (46%) developed chronic GvHD and three of them were extensive type. Of the three patients who died, two received SCT from HLA-matched sibling donors and died due to relapse at 8 and 10 months post-transplant, respectively; the other, who had received SCT from an HLA-matched unrelated donor, died at 7 months due to sepsis combined with extensive chronic GvHD in CR. The estimated 2-year overall survival and event-free survival rates were both 77%. We suggest that allogeneic SCT with this novel RIC for heterogeneous CBFA-AML patients is a feasible option with no detrimental post-transplant complications and less frequent relapse. Further, well-designed studies with more patients, comparing our regime to conventional high-dose chemotherapy, are needed to confirm these findings.