Busulfan, thiotepa, and melphalan as a conditioning regimen for allogeneic bone marrow transplantation in patients with acute myelogenous leukemia / 대한내과학회지

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the toxicity and efficacy of high-dose chemotherapy with busulfan, thiotepa and melphalan (BTM) as a myeloablative regimen in allogeneic bone marrow transplantation (allo-BMT) for patients with acute myelogenous leukemia (AML). METHODS: Twenty-seven patients with AML were enrolled; Sixteen patients had standard risk (SR) diseases (first complete remission (CR1) and de novo AML) and eleven patients had high risk (HR) diseases (second, or subsequent remission, secondary AML, relapsed, or refractory AML, CR marrow with persisting extramedullary manifestation (chloroma), or hypoplastic acute leukemia). The conditioning regimen included busulfan 4 mg/kg/day for a total dose of 12 mg/kg; thiotepa 250 mg/m2/day for a total dose of 500 mg/m2; and melphalan 50 mg/m2/day for a total dose of 100 mg/m2. Cyclosporine A and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. RESULTS: The median time to recovery a granulocyte count of 0.5 x 109/L was 14 days (range 10~25 days) and platelet transfusion independence was 30 days (range 12~49 days). The major regimen-related toxicities were gastrointestinal-related symptoms including oral mucositis, nausea, vomiting, and diarrhea. All patients experienced oral mucositis (> or = grade 1) and the patients with oral mucositis of equal and greater than grade 3 were 44% in SR and 45% in HR. The toxicities associated with lung, skin, heart and brain were minimal. Three (11%) patients had severe or fatal veno-occlusive disease (VOD). There were five treatment-related death (19%) (hepatic VOD with multiorgan failure (n=3), pneumonia and ARDS (n=2)) within the first 100 days after allo-BMT. There was not a significant difference between SR and HR group (p=0.167). The incidence of acute GVHD equal or greater than grade II was less than 10%. The actual survival at 2 year was 70.4%(95% confidence interval (CI), 54.7%~86.1%)(SR; 81.3% (95% CI; 63.4~99.1%) vs HR; 54.6% (95% CI; 28.7~80.4%), p=0.154). After a median follow-up of 630 days, 18 of 27 (67%, 355~1062 days) patients are alive without evidence of disease. Three of the 27 patients relapsed (SR; 0% vs HR; 55.6% (95% CI; 19.6~71.3%), p=0.004). CONCLUSION: The BTM regimen followed by allo-BMT is associated with acceptable toxicity and appears to have significant activity in patients with AML. It should be used with caution in patients with prior hepatopathy or refractory state who have an increased risk of severe VOD. Busulfan, thiotepa, and melphalan is an effective and alternative myeloablative regimen for patients with AML.