Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute 
myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor 
response to conventional cytotoxic chemotherapy. The purpose of our prospective 
single-center study was to examine the safety and efficacy of an allogeneic 
hematopoietic stem cell transplantation (HSCT) following a sequential 
conditioning regimen as first-line therapy for previously untreated patients 
with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 
high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 
100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA). After 2 to 3 days of rest, 
patients received high-dose melphalan alone (200 mg/m(2) for patients with an 
age <50 years, 150 mg/m(2) for patients with an age between 50 and 60 years, and 
100 mg/m(2) for patients with an age >60 years; n = 24) or melphalan and 
thiotepa (10 mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning 
regimens, a median number of 7.7 × 10(6) CD34(+) cells/kg body weight (range: 
2.9 × 10(6)-17.2 × 10(6)) were transplanted from 13 related or 17 unrelated 
donors. Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and 
mycophenolate mofetil were used for graft-versus-host disease (GVHD) 
prophylaxis. All patients except 1 with primary graft failure achieved complete 
remission after HSCT. After a median follow-up time of 28 months (range: 7-81), 
21 patients (70%) were alive and free of disease. Overall, 4 patients relapsed. 
At 2 years, overall survival, event-free survival, and treatment-related 
mortality were 70%, 63%, and 30%, respectively. Because of undue toxicity, 
thiotepa is no longer part of the conditioning regimen. Our results add to the 
body of evidence that a FLAMSA-based sequential conditioning therapy is 
effective for previously untreated patients with high-risk MDS or sAML.