A comparison of chimerism and minimal residual disease between four different allogeneic transplantation methods in patients with chronic myelogenous leukemia in first chronic phase.
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).
Elmaagacli
A H
AH
Department of Bone Marrow Transplantation, University Hospital Essen, Essen, Germany.
Runkel
K
K
Steckel
N
N
Opalka
B
B
Trenschel
R
R
Seeber
S
S
Schaefer
U W
UW
Beelen
D W
DW
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
D018952:Antigens, CD34; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl