Idarubicin intensified BUCY2 regimen in allogeneic unmanipulated transplant for high-risk hematological malignancies

Twenty-nine consecutive patients with high-risk hematological malignancy ag ed from 3 to 58 years underwent an unmanipulated graft from an HLA-identica l sibling after an irradiation-free preparative regimen consisting of idaru bicin (IDA), 21 mg/m(2)/day administered by continuous infusion on days -12 and -11, followed by busulphan (BU), 4 mg/kg/day orally from day -7 to -4, and cyclophosphamide (CY), 60 mg/kg/day intravenously on days 3 and -2 (ID A-BUCY2). Most clinically relevant extra-hematological regimen-related toxi cities consisted of stomatitis observed in all subjects and hemorrhagic cys titis occurred in five cases (17%) within 100 days after transplant. Six pa tients (21%) developed a grade 2 acute graft-versus-host disease (GVHD) and three (10%) a grade 3 or 4; extensive chronic GVHD was assessed in nine of 22 (41%) evaluable patients. So far, 12 patients have died and 17 are aliv e, 16 of whom disease-free, 5-41 months after transplant (median, 15 months ). The causes of death were related to GVHD in three patients, to sepsis in one and to disease recurrence in the remaining eight. At present, only one of nine relapsed patients is alive. For all patients the actuarial probabi lity of survival (OS) at 1 and 2 years+/-standard error (s.e.) was 63+/-9% and 52+/-10%, respectively. The actuarial probabilities of disease-free sur vival (DFS), relapse and transplant-related mortality (TRM) at both I and 2 years +/- s.e. were 53+/-9%, 35+/-9% and 16+/-7%, respectively. These resu lts are encouraging but not substantially different from those obtained in 28 patients with malignancy in advanced phase transplanted after the standa rd BUCY2 regimen, who had an actuarial probability of OS, DFS, relapse and TRM projected at 10 years+/-s.e. of 54+/-10%, 57+/-9%, 36+/-9% and 11+/-6%, respectively. Although the retrospective comparison between the two groups does not seem to show any advantage in the use of the IDA intensified regi men, only a prospective randomized trial could answer this question.