title: Rapid achievement of PML-RAR alpha polymerase chain reaction (PCR)-negativity by combined treatment with all-trans-retinoic acid and chemotherapy in acute promyelocytic leukemia: a pilot study.
abstract: The reverse transcriptase-polymerase chain reaction (RT-PCR) for the fusion transcript of PML-RAR alpha can be used to detect minimal residual disease (MRD) in acute promyelocytic leukemia (APL). We have applied a semi-quantitative two-step PCR assay (sensitivity: step 1 = 1 in 10(3) cells; step 2 = 1 in 10(6) cells) to monitor the dynamics of MRD after combined therapy with all-trans-retinoic acid (ATRA) and chemotherapy (CT) in 5 patients in whom complete clinical remission (CR) was achieved. The patients received an induction treatment with ATRA for 47, 40, 38, 14 or 10 days. In three patients ATRA was followed by CT. Two patients with hyperleukocytosis at diagnosis or after ATRA received an overlapping CT starting from day 3 or 7. Four of the five patients became two-step PCR-negative in their bone marrow within 43 to 82 days after onset of therapy. Two-step PCR-negatively was achieved with ATRA plus one course of CT in these four patients who are still in continuous complete remission after 19, 18, 7 and 5 months. One of these patients did not even receive consolidation CT because of congestive heart failure. The fifth patient remained second-step PCR-positive and relapsed after 5 months. Our results indicate that the combined regimen can rapidly reduce MRD below a detection limit of 1 in 10(6) cells within 1-3 months and that these results can even by achieved by a short course of ATRA together with only one cycle of CT.
authors.affiliation: Department of Medicine, University of Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Laczika
authors.forename: G
authors.initials: G
authors.lastname: Mitterbauer
authors.forename: L
authors.initials: L
authors.lastname: Korninger
authors.forename: P
authors.initials: P
authors.lastname: Knöbl
authors.forename: I
authors.initials: I
authors.lastname: Schwarzinger
authors.forename: S
authors.initials: S
authors.lastname: Kapiotis
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: P A
authors.initials: PA
authors.lastname: Kyrle
authors.forename: J
authors.initials: J
authors.lastname: Pont
authors.forename: L
authors.initials: L
authors.lastname: Oehler
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D002884:Chromosomes, Human, Pair 15 / Q000502:physiology*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics*; D008969:Molecular Sequence Data; D010865:Pilot Projects; D016133:Polymerase Chain Reaction / Q000379:methods*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D012680:Sensitivity and Specificity; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D003561:Cytarabine; D014212:Tretinoin; D003630:Daunorubicin