Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v. busulfan and cyclophosphamide (i.v. BuCy)

Pretransplant conditioning therapy with i,v, BuCy followed by allogeneic he matopoietic stem cell transplantation (BMT) was investigated in a phase II trial in patients with acute myeloid leukemia (ARIL) or myelodysplastic syn drome (MDS), We gave i,v, Bu at a dose of 0,8 mg/kg every 6h x 16 doses, fo llowed by Cy 60 mg/kg daily for 2 days, Twenty-six AML patients (18 males/e ight females) were treated, only eight of whom were in CR1, The rest were e ither refractory to induction chemotherapy (four patients) or in a more adv anced stage of their disease (14 patients), In addition, nine patients with MDS (1M/8F) were treated. Their median age was 41 years (range 21-64), Eng raftment to greater than or equal to 500 neutrophils/mu l was reached at 14 days (range 10-29 days) post BMT, and the median time of neutropenia was o nly 11 days (range 4-28 days). The most common regimen-related toxicity was grade 2-3 nausea, In the post-BMT period (including BMT day +30), two pati ents died, one each from pulmonary hemorrhage secondary to CMV pneumonia an d hepatic veno-occlusive disease (VOD), for an early treatment-related mort ality (TRM) of 5,7%, Three patients developed VOD and two of them died. The re was no direct regimen-related pulmonary or neurologic toxicity. Overall, the clinical side-effect spectrum was analogous to what would be expected from a high-dose oral Bu-based regimen; there was no unique toxicity experi enced with the used solvent system, The disease-free survival in the high-r isk subgroup tall patients not in CRI) at 1 and 2 years post transplant was 44% and 31%, respectively. The 13 patients still alive in CR have been fol lowed for a median of 24 months (range 18-32), Pharmacokinetic analysis sho wed very good interdose reproducibility, and limited interpatient variabili ty in area under the plasma concentration vs time curve, peak concentration , and clearance of Bu after this i,v, formulation, We conclude, that this n ew i,v, Bu formulation is well tolerated; it has an impressive safety profi le, and we suggest that it should be considered as appropriate replacement for oral busulfan in pretransplant conditioning therapy prior to allogeneic BMT for patients with AML or MDS.