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Clinical value of quantitative long-term assessment of bcr-abl chimeric transcript in chronic myelogenous leukemia patients after allogeneic bone marrow transplantation.

AbstractBACKGROUND AND 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.
DESIGN AND 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.
INTERPRETATION AND 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.
AuthorsG Martinelli, V Montefusco, N Testoni, M Amabile, G Saglio, E Ottaviani, C Terragna, F Bonifazi, G Rosti, G Bandini, S Tura
JournalHaematologica (Haematologica) Vol. 85 Issue 6 Pg. 653-8 (Jun 2000) ISSN: 0390-6078 [Print] Italy
PMID10870124 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Fusion Proteins, bcr-abl
Topics
  • Adolescent
  • Adult
  • Blast Crisis (genetics, therapy)
  • Bone Marrow Transplantation
  • Cytogenetics
  • Disease-Free Survival
  • Female
  • Fusion Proteins, bcr-abl (genetics)
  • Graft vs Leukemia Effect
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics, therapy)
  • Male
  • Middle Aged
  • Neoplasm, Residual (diagnosis, genetics, therapy)
  • Polymerase Chain Reaction
  • RNA, Messenger (blood)
  • Recombinant Fusion Proteins (genetics)
  • Transplantation, Homologous

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