Clinical value of quantitative long-term assessment of bcr-abl chimeric transcript in chronic myelogenous leukemia patients after allogeneic bone marrow transplantation.
OBJECTIVE
For purposes of therapeutic decision making, we used quantitative polymerase chain reaction (PCR) for molecular follow-up of 55 patients with chronic myeloid leukemia (CML) in complete remission (CR) after allogeneic bone marrow transplantation (BMT) from HLA compatible donors.


METHODS
A total of 402 bone marrow samples from 40 patients transplanted in chronic phase (group 1) and 15 in accelerated/blastic phase (group 2) were analyzed by qualitative and quantitative PCR.


RESULTS
Regarding clinical outcome, 34/40 (85%) group 1 vs. 8/15 (54%) group 2 patients are alive. Only 1/40 (2.5%) group 1 patient relapsed, as against 6/15 (40%) in group 2 (p = 0. 0002). At qualitative PCR, 8/40 (19%) group 1 vs. 9/15 (60%) group 2 patients were positive, with a significantly greater total number of positive samples in group 2 (33/129, 27% vs. 16/273, 5%; p<0.001). The probability of qualitative PCR positivity >1 year after BMT was significantly lower in group 1 patients (4/40 pts, 10% vs. 9/15 pts, 60%; p = 0.01). At quantitative PCR, 4/8 (50%) group 1 patients were positive only once (< 400 transcripts/microg RNA). In group 2, 9/15 (60%) patients had 3 or more positive samples (always with >4,000 copies/mg RNA); therapeutic interventions (cyclosporin A discontinuation, temporary a-interferon or donor lymphocyte infusion) restored molecular remission in 4/9 (44%) cases.


CONCLUSIONS
This study indicates that quantitative PCR could provide practical indications capable of directing therapeutic interventions for transplanted CML patients, especially those transplanted in accelerated/blastic phase, for whom intensive monitoring is required.
Martinelli
G
G
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, via Massarenti 9, 40138 Bologna, Italy. gmartino@kaiser.alma.uni-bo.it.
Montefusco
V
V
Testoni
N
N
Amabile
M
M
Saglio
G
G
Ottaviani
E
E
Terragna
C
C
Bonifazi
F
F
Rosti
G
G
Bandini
G
G
Tura
S
S
D000293:Adolescent; D000328:Adult; D001752:Blast Crisis / Q000235:genetics / Q000628:therapy; D016026:Bone Marrow Transplantation; D003582:Cytogenetics; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D020544:Graft vs Leukemia Effect; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000097:blood*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014184:Transplantation, Homologous
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016044:Fusion Proteins, bcr-abl