title: A comparison of chimerism and minimal residual disease between four different allogeneic transplantation methods in patients with chronic myelogenous leukemia in first chronic phase.
abstract: 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).
authors.affiliation: Department of Bone Marrow Transplantation, University Hospital Essen, Essen, Germany.
authors.forename: A H
authors.initials: AH
authors.lastname: Elmaagacli
authors.forename: K
authors.initials: K
authors.lastname: Runkel
authors.forename: N
authors.initials: N
authors.lastname: Steckel
authors.forename: B
authors.initials: B
authors.lastname: Opalka
authors.forename: R
authors.initials: R
authors.lastname: Trenschel
authors.forename: S
authors.initials: S
authors.lastname: Seeber
authors.forename: U W
authors.initials: UW
authors.lastname: Schaefer
authors.forename: D W
authors.initials: DW
authors.lastname: Beelen
mesh_terms: D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000592:standards; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D012074:Remission Induction; D015996:Survival Rate; D020080:Tandem Repeat Sequences; D018183:Transplantation Chimera / Q000097:blood*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000379:methods / Q000592:standards
chemical_list: D018952:Antigens, CD34; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl