Pathologic, cytogenetic and molecular assessment of acute promyelocytic leukemia patients treated with arsenic trioxide (As2O3)

Tao Zhang, Peter Westervelt, Jay L. Hess

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20 Scopus citations

Abstract

Arsenic trioxide (As2O3) shows great promise as an effective therapy for patient with all-trans retinoic acid (ATRA)-resistant acute promyelotic leukemia (APL). Little data is available adressing the pathology of As2O3 treated APL and whether the antileukemic mechanism of As2O3 is primarily cytolysis or through stimulation of cell differentiation. In this report, we made a morphologic, cytogenetic, and molecular evaluation of five ATRA-refractory APL patients who were treated with As2O3. Four of the five patients had morphologic responses after one or two cyces of As2O3 treatment. Of the four responders based on bone marrow morphology, two achieved molecular remission (negative RT-PCR for PML- RARα fusion transcripts) by the end of the second and third cycles of As2O3 therapy. Two patients exhibited marked leukocytosis during the first cycle of As2O3, and at that time point the APL cells were largely replaced by the cells showing partial differentiation towards myelocytes with co-expression of CD11b and CD33. Nevertheless, these 'myelocyte-like' cells that showed the t(15;17) tanslocation eventually disappeared with continuous As2O3 therapy. As2O3 treatment appears to be effective therapy for the patients with relapsed APL after the failure of conventional chemotherapy and ATRA therapy. The pathologic findings in these five cases suggest that at low doses As2O3 primarily induces differentiation of the APL cells, generating abnormal myelocytes resembling APL cells treated with ATRA, whereas at higher doses As2O3 induces marrow necrosis.

Original languageEnglish
Pages (from-to)954-961
Number of pages8
JournalModern Pathology
Volume13
Issue number9
DOIs
StatePublished - Jan 1 2000

Keywords

  • Acute promyelocytic leukemia
  • All-trans retinoic acid
  • Arsenic trioxide

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