Real-time PCR analysis of PML-RAR alpha in newly diagnosed acute promyelocytic leukaemia patients treated with arsenic trioxide as a front-line therapy.
BACKGROUND
Recently, patients with acute promyelocytic leukaemia (APL) have experienced significant clinical gains after treatment with arsenic trioxide. However, the use of this agent as a front-line therapy for newly diagnosed patients is unclear.


METHODS
Of 95 newly diagnosed APL patients, 85 patients who achieved complete remission (CR) were sequentially evaluated during a 4-60 month period by conventional RT-PCR. A total of 30 patients (six relapsed and 24 in continued CR) were selected and monitored by quantitative real-time PCR (RQ-PCR) assay. The PML-RARalpha fusion transcripts values were normalised to every 10(6) copies of G6PDH transcripts (NQ).


RESULTS
RQ-PCR analyses showed a rapid rate of clearance of NQ levels during the courses of arsenic therapy. In the majority of patients in CR, the NQ levels were below 5 x 10(2) in peripheral blood (PB) samples. In all the relapsed cases with follow-up intervals of 1-6 months (median 3 months) clinical relapse was predictable by increasing NQ level above this threshold.


CONCLUSIONS
Our study highlights the usefulness of PB and the definition of threshold level for early prediction of relapse. The threshold level correlates well with risk of relapse; therefore, transcript ratio below the level should be regarded as a goal in the clinical management of this disease.
Ghaffari
S H
SH
Hematology, Oncology and BMT Research Center, Tehran University Medical Sciences, Shariaty Hospital, Tehran, Iran. shghaffari2000@yahoo.com
Rostami
S
S
Bashash
D
D
Alimoghaddam
K
K
Ghavamzadeh
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002648:Child; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000379:methods; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000378:metabolism; D010087:Oxides / Q000627:therapeutic use*; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
D000970:Antineoplastic Agents; D001152:Arsenicals; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D010087:Oxides; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D005954:Glucosephosphate Dehydrogenase; D000077237:Arsenic Trioxide