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The PML-RAR alpha transcript in long-term follow-up of acute promyelocytic leukemia patients

Gameiro, P; Vieira, S; Carrara, P; Silva, AL; Diamond, J; de Sousa, AB; Mehta, AB; ... Parreira, A; + view all (2001) The PML-RAR alpha transcript in long-term follow-up of acute promyelocytic leukemia patients. Haematologica , 86 (6) 577 - 585. Green open access

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Abstract

Background and Objectives. Detection of PML-RAR alpha transcripts by RT-PCR is now established as a rapid and sensitive method for diagnosis of acute promyelocytic leukemia (APL), Although the majority of patients in longterm clinical remission are negative by consecutive reverse transcription polymerase chain reaction (RT-PCR) assays, negative tests are still observed in patients who ultimately relapse. Conversion from negative to positive PCR has been observed after consolidation and found to be a much stronger predictor of relapse. This study reports on 47 APL patients to determine the correlation between minimal residual disease (MRD) status and clinical outcome in our cohort of patients. Design and Methods. The presence of PML-RAR alpha t transcripts was investigated in 47 APL patients (37 adults and 10 children) using a semi-nested reverse transcriptase-polymerase chain reaction to evaluate the prognostic value of RT-PCR tests. Results. All patients achieved complete clinical remission (CCR) following induction treatment with all-trans retinoic acid (ATRA) and chemotherapy (CHT) or ATRA alone. Patients were followed up between 2 and 117.6 months (median: 37 months). Relapses occurred in 11 patients (9 adults and 2 children) between 11.4 and 19 months after diagnosis (median: 15.1 months) while 36 patients (28 adults and 8 children) remained in CCR, Seventy-five percent of patients carried the PML-RARa long isoform (bcr 1/2) which also predominated among the relapsed cases (9 of 11) but did not associate with any adverse outcome (p = 0.37), For the purpose of this analysis, minimal residual disease tests were clustered into four time-intervals: 0-2 months, 3-5 months, 5-9 months and 10-24 months. Interpretation and Conclusions. Children showed persisting disease for longer than adults during the first 2 months of treatment, At 2 months, 10 (50%) of 20 patients who remained in CCR and 4 (80%) of 5 patients who subsequently relapsed were positive. Patients who remained in CCR had repeatedly negative results beyond 5.5 months from diagnosis. A positive MRD test preceded relapse in 3 of 4 tested patients. The ability of a negative test to predict CCR (predictive negative value, PNV) was greater after 6 months (> 83%), while the ability of a positive test to predict relapse (predictive positive value, PPV) was most valuable only beyond 10 months (100%). This study (i) highlights the prognostic value of RT-PCR monitoring after treatment of APL patients but only from the end of treatment, (ii) shows an association between conversion to a positive test and relapse and (iii) suggests that PCR assessments should be carried out at 3-month intervals to provide a more accurate prediction of hematologic relapses but only after the end of treatment, (C) 2001, Ferrata Storti Foundation

Type: Article
Title: The PML-RAR alpha transcript in long-term follow-up of acute promyelocytic leukemia patients
Open access status: An open access version is available from UCL Discovery
Publisher version: http://www.haematologica.org/content/86/6/577.full...
Language: English
Additional information: Journal English Article FERRATA STORTI FOUNDATION JUN 446QX PAVIA HAEMATOLOGICA STRADA NUOVA 134, 27100 PAVIA, ITALY. Obtained from Haematologica/the Hematology Journal website http://www.haematologica.org" This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Ability, Acid, Adult, Adults, Adverse, Alpha, Analysis, aPL, As, Assay, Assays, Assessment, Assessments, Association, Chain, Chain-reaction, Chemotherapy, Children, Clinical, Cohort, Complete, Conversion, Correlation, Design, Detection, Diagnosis, Disease, End, English, Follow up, Follow-up, Foundation, Fusion messenger-RNA, Gene, Induction, Interpretation, Isoform, Italy, Jun, Leukemia, Leukemia patients, Long, long term follow up, Long-term, Methods, Minimal residual disease, Molecular remission, monitoring, MRD, negative, outcome, Patient, patients, PCR, Polymerase, Polymerase chain reaction, Polymerase chain-reaction, Polymerase-chain-reaction, Positive, Prediction, predictor, Rognostic, Prognostic value, RAR alpha, Reaction assay, Relapse, Remission, Report, Reports, Result, Retinoic acid, Reverse Transcriptase Polymerase Chain Reaction, reverse transcription, Reverse Transcription Polymerase Chain Reaction, RT-PCR, sensitive, T(15-17) translocation, tests, transcription, transcripts, treatment
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/26479
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