Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia

Sixty-two adults underwent marrow or blood stem cell transplantation from a n HLA-matched related donor using high-dose thiotepa, busulfan, and cycloph osphamide (TBC) as the preparative regimen for treatment of advanced myelod ysplastic syndrome (MDS) (refractory anemia with excess blasts with or with out transformation) or acute myelogenous leukemia (AML) past first remissio n. AH evaluable patients engrafted and had complete donor chlmerism. A grad e 3-4 regimen-related toxicity occurred in eight (13%) patients, and a diag nosis of MDS was the only independent risk factor for grade 3-4 regimen-rel ated toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mort ality (TRM) was 19%. Poor-prognosis cytogenetics increased the risk of day- 100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-ver sus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43% (95 % CI, 28%-58%). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard rati o 10.8, P = 0.02). Three-year survival was 26% (95% CI, 14%-37%); survival rates were 29% for those transplanted for AML in second remission, 31% tran splanted for AML in relapse, and 17% with MDS, and there were no independen t risk factors for survival. TBC is an active preparative regimen for advan ced AML. Patients with advanced MDS appeared to have a higher risk of toxic ity and early mortality, and alternative preparative regimens should be con sidered for these patients. (C) 2001 Wiley-Liss, Inc.