Clinico-biological features and outcome of acute promyelocytic leukemia patients with persistent polymerase chain reaction-detectable disease after the AIDA front-line induction and consolidation therapy.
OBJECTIVE
Front line treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and chemotherapy (CHT) results in molecular remission in approximately 95% of patients tested after consolidation. The small fraction of patients with persistence of molecular disease (i.e. those in whom polymerase chain reaction (PCR) is positive for PML/RARalpha) after such therapy are thought to have a dismal prognosis but has not yet been investigated in detail.


METHODS
We analyzed the clinico-biological features at presentation of APL patients who showed PCR-detectable residual disease and compared them to those of patients achieving molecular remission after AIDA induction and consolidation. Furthermore, we report the outcome of patients with molecularly persistent disease treated with salvage therapy.


RESULTS
Patients attaining molecular remission (n=650) and patients who tested PCR+ve at the end of consolidation (n=23) were not statistically significantly different as regards median age, white cell and platelet counts, morphologic subtype (M3 or M3v), fibrinogen levels or PML/RARalpha transcript type. As to treatment outcome after salvage therapy, 7 patients were treated before morphologic relapse [3 with chemotherapy and autologous stem cell transplantation (SCT) and 4 with allogeneic SCT], and are alive after 64-118 months. Of 16 patients treated at the time of morphologic relapse, only 2 patients are alive, both of whom received an allogeneic SCT.


CONCLUSIONS
Our findings indicate that APL patients who are molecularly resistant to the AIDA protocol have no distinguishing features at presentation. Their outcome suggests the need for early therapeutic intervention with aggressive treatment prior to the occurrence of hematologic relapse.
Breccia
Massimo
M
Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma, Italy.
Diverio
Daniela
D
Noguera
Nélida Inés
NI
Visani
Giuseppe
G
Santoro
Alessandra
A
Locatelli
Franco
F
Damiani
Daniela
D
Marmont
Filippo
F
Vignetti
Marco
M
Petti
Maria C
MC
Lo Coco
Francesco
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009363:Neoplasm Proteins / Q000235:genetics; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D012074:Remission Induction; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D015255:Idarubicin