Early detection of minimal residual disease by reverse transcriptase polymerase chain reaction predicts relapse in acute promyelocytic leukemia.
The PML/RAR alpha fusion RNA can be detected in acute promyelocytic leukemia (APL), cytogenetically characterized by the translocation t(15;17). Our study included ten newly diagnosed patients with APL who were investigated during the course of their diseases using reverse transcription polymerase chain reaction (RT-PCR). At diagnosis, aberrant fragments with a size heterogeneity due to alternative spliced products were detected in all patients, we observed breakpoints within bcr3 (short type) in two patients and bcr1 and 2 breakpoints (long type) in eight patients. Treatment consisted of all-trans retinoic acid (ATRA) in all patients; six patients received simultaneous cytostatic therapy during remission induction. At the time of complete hematological remission (CR), only two patients showed a negative RT-PCR result; eight of the ten patients were still PCR positive when nested primers were used. Subsequently, eight patients received consolidation chemotherapy and became PCR negative. Seven of eight patients are in continuous complete remission (median remission duration: 21 months, range: 11+ -26+ months). One patient of the chemotherapy group became PCR positive after 4 months in complete remission and relapsed after 6 months. The remaining two patients who were treated only with ATRA relapsed, received induction chemotherapy, and are in second and third complete remission, respectively. In conclusion. PCR negativity can be achieved only by chemotherapeutic consolidation; patients treated with ATRA alone remain PCR positive. Relapse is always preceded by a positive PCR result. Surprisingly, also patients without measurable PML/RAR alpha-mRNA in sequential analyses after cytostatic treatment became PCR positive and experienced relapse.
Koller
E
E
3rd Medical Department, Hanusch Hospital, Vienna, Austria.
Karlic
H
H
Krieger
O
O
Mistrik
M
M
Michlmayr
G
G
Gadner
H
H
Lutz
D
D
Heinz
R
R
Pittermann
E
E
D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D012008:Recurrence; D012074:Remission Induction; D000072482:Retinoic Acid Receptor alpha; D013997:Time Factors; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use
D017931:DNA Primers; D015342:DNA Probes; D004273:DNA, Neoplasm; C000607071:RARA protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin