A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome

A. Quintá-Cardama, L. V. Abruzzo, F. J. Giles, J. Jorgensen, J. Cortes, J. E. Sarriera, H. Kantarjian, S. Verstovsek

Research output: Contribution to journalLetter

2 Scopus citations

Abstract

Indications:1 patient with refractory acute myelogenous leukemia.

Patients:One 62-year-old male patient (outpatient and inpatient).

TypeofStudy:This case report described the outcome TP AMN107 (Tasigna) treatment in a patient with acute myelogenous leukemia (AML) who developed a novel translocation t(3;21)(p21;q22) and Philadelphia chromosome (Ph)-positivity during PTK787 + imatinib mesylate treatment. Letter to the Editor.

DosageDuration:400 mg bid (=800 mg daily). Duration not stated.

Results:TP AMN107 treatment was completely unsuccessful. A few days following the commencement of TP AMN107, antibiotic and antifungal treatments, mucormycosis was detected. Despite of the high-dose liposomal amphotericin B and caspofungin treatments, the patient died shortly thereafter.

AdverseEffects:No adverse events were mentioned.

AuthorsConclusions:This patient failed therapy with high-dose imatinib and subsequently with AMN107 [TP AMN107], an Abl1 kinase inhibitor 30-fold more potent than imatinib. Because imatinib is associated with hematologic responses in 52% of patients with CML [chronic myelogenous leukemia] in myeloid blast phase, and AMN107 is associated with hematologic response in 57% of patients who had previously failed imatinib, the lack of response was unexpected. Regardless, our observations suggest that a late-appearing Ph chromosome in patients with AML may represent a secondary event that is related to chemotherapy, particularly topoisomerase II inhibitors, and which confers a poor prognosis and lack of response to tyrosine kinase inhibitors.

FreeText:The patient presented with persistent pancytopenia. He was diagnosed with AML in August 2002 and treatment with cytarabine (ara-C) and idarubicin (7+3 regimen) achieved complete remission. Two months following high-dose ara-C (HDAC), bone marrow aspirate showed tri-lineage dysplasia with 3% blasts. In August 2004, the patient relapsed and bone marrow aspirate revealed 28% blasts. Following 7+3 treatment, pancytopenia again developed. HDAC and fludarabine was instituted and 3 months later, bone marrow demonstrated 10% blasts. In May 2005, bone marrow examination revealed 62% blasts and cytogenetic analysis showed 46,XY,t(3;21)(p21;q22) in eight metaphase. Treatments included mitoxantrone, suberoylanilide hydroxamic acid, and hydroxyurea. In August 2005, bone marrow showed hypercelullarity with 83% blasts and karyotypic evaluation revealed 46,XY,t(9;22)(q34;q11.2)[17]/46,XY,der(9) t(9,22)(q34;q11.2) inv(9)(p12q32), der(22) t(9;22)[2]/46,XY. Fluorescence in situ hybridization (FISH) of the BCR/ABL1 demonstrated double-fusion signals in 92.5% of the interphases. Treatment with imatinib mesylate (600 mg daily) and PTK787 was initiated. On day 28, bone marrow aspirate revealed 62% blasts and karyotypic analysis demonstrated 46,XY,t(9;22)(q34;q11.2)[18]/46,XY,der(9)inv(9)(p12q32)t(9,22)(q34;q11.2 ),der(22) t(9;22)[1]. Because of lack of response, treatment with imatinib mesylate and PTK787 was withdrawn and TP AMN107 was commenced. Concomitant treatments were broad-spectrum antibiotics, antifungals (including liposomal amphotericin and caspofungin), leukocyte transfusion. Other test: real-time polymerase chain reaction and fine needle aspiration biopsy (lung).

Original languageEnglish (US)
Pages (from-to)1638-1640
Number of pages3
JournalLeukemia
Volume20
Issue number9
DOIs
StatePublished - Sep 2006

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Quintá-Cardama, A., Abruzzo, L. V., Giles, F. J., Jorgensen, J., Cortes, J., Sarriera, J. E., Kantarjian, H., & Verstovsek, S. (2006). A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome. Leukemia, 20(9), 1638-1640. https://doi.org/10.1038/sj.leu.2404283