Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Currently available clinical results show that the combination of ATRA and anthracycline-Ara-C chemotherapy can slightly increase the CR rate in newly diagnosed APL, from about 80% (with chemotherapy alone) to more than 90%, and patients presenting with high leukocyte counts seem to benefit particularly from this combined therapy. ATRA followed by chemotherapy also reduces the incidence of relapse (particularly of early relapse) as compared to chemotherapy alone. However, treatment with ATRA is still complicated by the risk of hyperleukocytosis and potentially fatal ATRA syndrome, whose best preventive approach (addition of chemotherapy and/or dexamethasone) is still debated. Because some patients still relapse after ATRA plus chemotherapy, prognostic factors for relapse need to be precisely determined. They certainly include persistence or re-appearance of PML-RAR transcript during follow-up. Allogeneic BMT should be considered in those patients. Most of the patients who are not cured by the combination of ATRA and chemotherapy or by subsequent allogeneic BMT still die from their disease. This is due to the acquisition by APL cells of progressive resistance to ATRA, that appears to depend on induction of increased ATRA catabolism in APL cells. Current efforts aimed at overcoming this resistance (including intermittent ATRA schedules, synthesis of new retinoid compounds, utilization of inhibitors of cytochrome P450) are being developed.
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PMID:Treatment of acute promyelocytic leukaemia. 873 May 53

Twenty patients with APL in long-term remission after BMT were analyzed for the presence of the PML-RAR alpha fusion gene by RT-PCR. Ten patients had undergone autologous BMT (six of them peripheral blood stem cell transplantation) and 10 allogeneic BMT. A total of 60 samples were examined by two different protocols. Of the eight patients studied just before conditioning, five showed PML-RAR alpha transcript prior to transplantation. Three of them were in CR and became PCR negative early post-transplantation. The other two patients, that were not in CR before transplant, remained PCR positive, relapsed early post-transplant and died. In the remaining patients no PML-RAR alpha transcripts were visible throughout their post-BMT courses. Our data show that long-term remission after BMT in APL patients is associated with eradication of cells carrying the PML-RAR alpha transcript, and that continued positivity of this test predicts subsequent relapse. The fact of the disappearance of PML-RAR alpha transcript early after BMT in patients previously positive suggest that transplant is capable of curing APL mainly through antileukemic action of the conditioning regimen and therefore, transplantation must be indicated in CR patients if a positive RT-PCR remains after treatment with ATRA plus chemotherapy.
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PMID:Absence of detectable PML-RAR alpha fusion transcripts in long-term remission patients after BMT for acute promyelocytic leukemia. 915 44