We present a phase II study of fludarabine 5 x 30 mg/m(2), thiotepa 3 x 5 mg/kg as preparative regimen specifically for allogeneic second haematopoietic stem cell transplantation (HCT) after failure of previous HCT. Forty-nine patients (median age 52 years, range 27-68) received an allogeneic second HCT after failed autologous (n=29) or allogeneic (n=20) HCT. Diagnoses were AML (n=18), ALL (n=3), multiple myeloma (n=11), lymphoma (n=16) and CML (n=1). GVHD prophylaxis consisted of CYA and mainly low dose alemtuzumab (40 mg). The median follow-up for patients alive is 528 days (range 217-1344). In 43 of 49 (88%) evaluable patients response rates were CR=19, PR=14 and SD=10 at one month. At one year, the probability (95% confidence interval) of relapse is 55.1 (38.2-72)% and the nonrelapse mortality (NRM) is 29 (14.2-44.4)%. Estimated survival at one year is 42.6 (28.7-56.6)% and event free survival is 38.1 (24.4-51.8)%. Survival was significantly better for patients experiencing relapse beyond one year, than for patients relapsing within one year from first transplantation (51.2 (33.5-68.9)% vs 27 (7-48.5)%; P=0.013). We conclude that this regimen is feasible and well tolerated for allogeneic second HCT.