Hematopoietic stem cell transplantation for childhood myeloid malignanciesafter high-dose thiotepa, busulfan and cyclophosphamide

Seventeen children with advanced myeloid malignancies (induction failure, r elapse, myelodysplasia, secondary AML, or CR >1) received thiotepa 750 mg/m (2) i.v., busulfan 12 mg/kg or 640 mg/m(2) p.o., and cyclophosphamide 120 m g/kg i.v. as a preparative regimen for allogeneic or autologous hematopoiet ic stem cell (HSC) transplantation. Of the 15 allogeneic transplants, eight were from matched siblings, one was from a mismatched sibling, and six wer e from unrelated donors. Graft-versus-host disease (GVHD) prophylaxis consi sted of cyclosporine or tacrolimus and methotrexate, Regimen-related toxici ty was common but tolerable, affecting mainly the skin and gastrointestinal tract. Three patients died early and were not evaluable for engraftment; e ngraftment occurred in the remaining patients. Nine patients with active di sease at the time of transplant were evaluable for response; all achieved r emission. With a median follow-up of 40 months (range, 10-71 months), nine patients are alive and disease-free. The 3-year actuarial event-free surviv al was 51% (95% confidence interval (CI) 27-76%), Seven patients died of tr ansplant-related complications: infection (n = 4), chronic GVHD (n = 1), ve no-occlusive disease, VOD, (n = 1) and pulmonary alveolar hemorrhage (n = 1 ), Only one patient had leukemia relapse and died. We conclude that the use of high-dose thiotepa, busulfan and cyclophosphamide is an effective condi tioning regimen for childhood myeloid malignancies and may be tested in pat ients with less advanced disease (eg CR1).