Adding busulfan with cyclophosphamide - total body irradiation as preparative regimen for allogeneic transplantation reduced relapse rate in myeloid leukemia.

O Asai, S Yano, A Kato, H Watanabe, M Katori, M Nagamine, N Maki, N Tajima, S Goto, N Hirabayashi, Y Kuraishi


Combination of cyclophosphamide (CY, 120 mg/kg) and fractionated total body irradiation (TBI, 12 Gy) (CY-TBI) is one of standard preparative regimen for bone marrow transplantation (BMT). The major problem that limits the success of this regimen is the posttransplant relapse. We investigated the effects of adding busulfan (BU) with CY-TBI followed by allogeneic BMT in myeloid leukemia.Patients and Methods: Forty-eight patients with acute myeloid leukemia (AML) or chronic myelogenous leukemia (CML) were transplanted between Oct. 1988 and Jun. 1997. Patients were administrated with BU (8 mg/kg po), fractionated TBI (10 Gy) and CY (120 mg/kg div). Median age of patients were 38-y-o (18-52), and 3.6 x 106/kg (2.8-6.0) of bone marrow nuclear cells were harvested from HLA identical siblings. The combination of cyclosporine and methotrexate was used for graft-vs-host disease (GvHD) prophylaxis.Results:Hematologic studies demonstrated donor engraftment in all patients. Grade I, II, III or IV of acute GvHD was 62.5%, 6.3%, 2.1%, 0%, and limited or extended chronic GvHD was 11.6%, 9.3% respectively. Relapse rate was 0% in standard risk group (AML 1st complete remission (CR); 9, CML 1st chronic phase (CP); 17) and 13.6% in poor risk group (AML induction failure, relapse, ³2nd CR; 14, CML 2nd CP, accelerated phase, blastic crisis; 8). The rate of grade ³1 regimen related toxicity (RRT) was as followed; cardiac 6.5% (grade ³3; 2.2%), pulmonary 13.0% (6.5%), hepatic 32.6% (2.2V), bladder 21.7% (0%), renal 2.2% (0%), CNS 0% (0%), stomatitis 100% (0%), G-I 84.8% (0%). Six patients were suffered from IP (cytomegalovirus (CMV); 4, GvHD; 1, RRT; 1), and 3 died of IP in standard risk group. Five patients were suffered from IP (CMV; 1, aspergillus; 1, RRT; 3), and 2 died of IP in poor risk group. Five-yrs-disease free survival was 76.1% in standard risk group and 55.8% in poor risk group.Conclusions:These data suggest that adding BU with CY-TBI as preparative regimen markedly enhance anti-tumor effects and reduce post-transplant relapse. Therefore, BU-CY-TBI appears to be an attractive preparative regimen for myeloid leukemia.

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39th meeting of the American Society for Haemotology
    • ASH 39th (1998)