All- trans-retinoic-acid and arsenic trioxide induced remission in promyelocytic blast crisis

Abstract

A 78-year-old-male with chronic myeloid leukemia (CML) treated for seven years with dasatinib developed an acute promyelocytic leukemia complicated by disseminated intravascular coagulopathy. A promyelocytic blast crisis was diagnosed by demonstrating co-expression of chimeric BCL/ABL and PML/RARα translocations by karyotyping, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction. Promyelocytic blast crisis of CML is a rare event with historically poor outcomes. Treatment of our patient with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) resulted in complete morphologic remission. We review here the relevant literature of promyelocytic blast crisis and highlight the potential of ATRA/ATO as first line management.

Keywords: ATO; ATRA; Blast crisis; CML; Promyelocytic.

Fig. 1

Chronic myeloid leukemia – blast crisis characterization (A) Increased promyelocytes seen in bone marrow aspirate using hematoxylin and eosin (H&E) staining; photographed at 1000x magnification (B) Conventional cytogenetics demonstrated an abnormal karyotype - 46, XY, t(9;22)(q34;11.2), t(15;17)(q24;q21). Fluorescent in situ hybridization (FISH) confirmed the presence of (C) t(9;22)(q34;q11.2)/BCR-ABL, and (D) t(15;17)(q24;q21)/PML-RARA fusions.

Fig. 2

Laboratory parameters of our patient demonstrating response of promyelocytic blast crisis to dual targeted therapy (A) Markers of disseminated intravascular coagulation (DIC) – fibrinogen and D-dimer - improved with ATRA-ATO therapy and normalized by day 5, (B) Peripheral blood myeloblast and promyelocte fractions of total white blood cell (WBC) count decreased gradually and were completely eliminated by day 16, and (C) PML-RARA and BCR-ABL transcript levels, assessed using quantitative real time polymerase chain reaction (qRT-PCR), decreased and demonstrated efficacy of ATRA-ATO therapy.