Clinico-biological features and outcome of acute promyelocytic leukemia patients with persistent polymerase chain reaction-detectable disease after AIDA front-line induction and consolidation therapy

Massimo Breccia, Daniela Diverio, Nélida Inés Noguera, Giuseppe Visani, Alessandra Santoro, Franco Locatelli, Daniela Damiani, Filippo Marmont, Marco Vignetti, Maria C. Petti, Francesco Lo Coco

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. Front-line treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and chemotherapy 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/RARα) after such therapy are thought to have a dismal prognosis but this has not yet been investigated in detail. Design and 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/RARα 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 had received an allogeneic SCT. Interpretation and 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.

Original languageEnglish
Pages (from-to)29-33
Number of pages5
JournalHaematologica
Volume89
Issue number1
Publication statusPublished - Jan 2004

Keywords

  • Acute promyelocytic leukemia
  • Persistent residual disease
  • PML/RARα

ASJC Scopus subject areas

  • Hematology

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