The detection of chimerism, residual molecular and cytogenetic disease following transplantation of peripheral blood stem cells (PBSCT) with a nonmyeloablative conditioning (n = 9) and the transplantation of highly purified CD34(+) stem cells (CD34(+) PBSCT) (n = 16) were compared to unmanipulated bone marrow transplantation (BMT) (n = 69) and unmanipulated PBSCT (n = 50) after myeloablative conditioning in patients with first chronic phase of chronic myelogenous leukemia (CML) (n = 137), second chronic phase of CML (n = 4), acute lymphoblastic leukemia (n = 2) and acute myeloid leukemia (n = 1). A molecular relapse (MR) as defined by two consecutive positive polymerase chain reaction assays for the detection of M-bcr-abl transcripts (n = 141) and cbfbeta-myh11 transcripts (n = 1) in a 4-week interval was found in 10 of 16 patients (63%) after CD34(+) PBSCT, and in 27 of 69 patients (39%) after BMT, whereas only three of 50 patients (6%) after PBSCT (P < 0.001) and one of eight patients (13%) after PBSCT with reduced conditioning suffered from a MR. A cytogenetic relapse occurred in five of 16 patients (31%) after CD34(+)PBSCT and 21 of 69 patients (30%) after BMT (NS) compared to two of 50 patients (4%) after PBSCT and none of the eight patients after PBSCT with reduced conditioning (P < 0.05). The lowest treatment-related mortality was seen in the 16 patients after CD34(+) PBSCT, who are all currently alive with a median follow-up of 15 months, whereas the survival rate for BMT, PBSCT and PBSCT with reduced conditioning were 65%, 63% and 58%, respectively. Multivariate analysis including all potential influential factors of post-transplant residual disease recurrence showed that patients after CD34(+) PBSCT had a significantly higher risk (two times) to develop a MR than patients after BMT (P < 0.03), whereas patients after unmanipulated PBSCT had a significant lower risk (eight times) for the occurrence of a MR post transplant (P < 0.001). Patients after BMT and CD34(+) PBSCT had the lowest rates of complete chimerism (CC) at 3 months after transplant. Only five of nine patients (55%) after CD34(+) PBSCT and 19 of 33 patients (58%) after BMT achieved CC compared to 19 of 22 (86%) patients after PBSCT and seven of eight (88%) patients after PBSCT with reduced conditioning (P < 0.05).