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

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
Externally publishedYes

Fingerprint

Philadelphia Chromosome
Acute Myeloid Leukemia
Cytarabine
caspofungin
Bone Marrow
Therapeutics
Pancytopenia
Antifungal Agents
Leukocyte Transfusion
Idarubicin
Topoisomerase II Inhibitors
Mucormycosis
Bone Marrow Examination
Blast Crisis
Mitoxantrone
Hydroxyurea
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Cytogenetic Analysis
Interphase
Amphotericin B

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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

A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome. / Quintá-Cardama, A.; Abruzzo, L. V.; Giles, F. J.; Jorgensen, J.; Cortes, J.; Sarriera, J. E.; Kantarjian, H.; Verstovsek, S.

In: Leukemia, Vol. 20, No. 9, 09.2006, p. 1638-1640.

Research output: Contribution to journalLetter

Quintá-Cardama, A, Abruzzo, LV, Giles, FJ, Jorgensen, J, Cortes, J, Sarriera, JE, Kantarjian, H & Verstovsek, S 2006, 'A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome', Leukemia, vol. 20, no. 9, pp. 1638-1640. https://doi.org/10.1038/sj.leu.2404283
Quintá-Cardama, A. ; Abruzzo, L. V. ; Giles, F. J. ; Jorgensen, J. ; Cortes, J. ; Sarriera, J. E. ; Kantarjian, H. ; Verstovsek, S. / A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome. In: Leukemia. 2006 ; Vol. 20, No. 9. pp. 1638-1640.
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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).",
author = "A. Quint{\'a}-Cardama and Abruzzo, {L. V.} and Giles, {F. J.} and J. Jorgensen and J. Cortes and Sarriera, {J. E.} and H. Kantarjian and S. Verstovsek",
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T1 - A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome

AU - Quintá-Cardama, A.

AU - Abruzzo, L. V.

AU - Giles, F. J.

AU - Jorgensen, J.

AU - Cortes, J.

AU - Sarriera, J. E.

AU - Kantarjian, H.

AU - Verstovsek, S.

PY - 2006/9

Y1 - 2006/9

N2 - 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).

AB - 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).

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