Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy [17]

A. Quintás-Cardama, H. Kantarjian, L. V. Abruzzo, J. Cortes

Research output: Contribution to journalLetter

Abstract

AuthorsConclusions:The present case illustrates the increasing recognition of cytogenetic abnormalities in Ph-negative cells in patients with CML treated with TKIs [tyrosine kinase inhibitors], and their association with progression to MDS [myelodysplastic syndrome] or AML. Moreover, it suggests that these abnormalities are not exclusively limited to the bone marrow and underscores the importance of close cytogenetic monitoring of these patients, to allow for an early detection of these rare aberrancies.

DosageDuration:400 mg bid (=800 mg daily) orally. Duration: 8 weeks.

Results:Over the next 8 weeks of Tasigna therapy, new nodular skin lesions appeared on his arms, back, legs, and abdomen. Bone marrow biopsy revealed 6% blasts, which were consistent with CML in chronic phase. Cytogenetic evaluation showed two clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)q(35),add(11)add(11)(p11.2) in 17 metaphases and a normal diploid male karyotype in 3 metaphases. BCR-ABL/ABL1 ratio in the peripheral blood decreased to 2.90%. Immunohistochemical analysis of a biopsied material from the inner thigh showed blasts cells positive for CD68 and negative for myeloperoxidase, CD117, and CD34, which was similar to his previous skin biopsy. FISH revealed no BCR-ABL1 rearrangement, but showed either deletion of an ABL1 gene or monosomy 9. Tasigna therapy was discontinued and systemic chemotherapy for induction of AML remission was instituted.

AdverseEffects:No adverse events were mentioned.

FreeText:The patient presented with skin lesion in his left knee (May 2005). Excisional biopsy was consistent with a hematologic disease. Bone marrow and core biopsies were consistent with CML in chronic phase. Fluorescence in situ hybridization (FISH) revealed the presence of Ph-positivity in 95% of the interphase nuclei evaluated. Treatment with imatinib was started. In October 2005, knee lesions recurred and biopsy was reported as acute myeloid leukemia (AML). In February 2006, cytogenetic analysis showed the presence of three clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),der(11)add(11)(p11.2) in 14 metaphases; 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),t(9;22)(q34;q11.2),add(11)(p11 .2) in 3 metaphases; and a normal diploid male karyotype in 3 metaphases. FISH confirmed the translocation of chromosome 11 materials to the short arm of one of the two chromosome 7 and demonstrated that 11.5% of the interphase nuclei were positive for translocation (BCR/ABL1 rearrangement). Bone marrow analysis revealed a BCR-ABL1/ABL1 ratio of 15.26%. New skin lesions in the upper arm appeared, which was negative for BCR-ABL1 rearrangement. Treatment with Tasigna was commenced.

Indications:1 patient with Philadelphia chromosome negative chronic myeloid leukemia.

Patients:One 73-year-old male patient.

TypeofStudy:This case report described the outcome of Tasigna therapy in a patient with cutaneous Philadelphia-chromosome (Ph) negative chronic myeloid leukemia (CML) lesions. Letter to the Editor.

Original languageEnglish (US)
Pages (from-to)2394-2396
Number of pages3
JournalLeukemia
Volume21
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Myeloid Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosome Aberrations
Metaphase
Philadelphia Chromosome
Clone Cells
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Biopsy
Skin
Bone Marrow
Fluorescence In Situ Hybridization
Acute Myeloid Leukemia
Leukemia, Myeloid, Chronic Phase
Arm
Interphase
Diploidy
Karyotype
Cytogenetics
Knee
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

@article{c98efacb03eb44a8a741e2e607c8711e,
title = "Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy [17]",
abstract = "AuthorsConclusions:The present case illustrates the increasing recognition of cytogenetic abnormalities in Ph-negative cells in patients with CML treated with TKIs [tyrosine kinase inhibitors], and their association with progression to MDS [myelodysplastic syndrome] or AML. Moreover, it suggests that these abnormalities are not exclusively limited to the bone marrow and underscores the importance of close cytogenetic monitoring of these patients, to allow for an early detection of these rare aberrancies.DosageDuration:400 mg bid (=800 mg daily) orally. Duration: 8 weeks.Results:Over the next 8 weeks of Tasigna therapy, new nodular skin lesions appeared on his arms, back, legs, and abdomen. Bone marrow biopsy revealed 6{\%} blasts, which were consistent with CML in chronic phase. Cytogenetic evaluation showed two clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)q(35),add(11)add(11)(p11.2) in 17 metaphases and a normal diploid male karyotype in 3 metaphases. BCR-ABL/ABL1 ratio in the peripheral blood decreased to 2.90{\%}. Immunohistochemical analysis of a biopsied material from the inner thigh showed blasts cells positive for CD68 and negative for myeloperoxidase, CD117, and CD34, which was similar to his previous skin biopsy. FISH revealed no BCR-ABL1 rearrangement, but showed either deletion of an ABL1 gene or monosomy 9. Tasigna therapy was discontinued and systemic chemotherapy for induction of AML remission was instituted.AdverseEffects:No adverse events were mentioned.FreeText:The patient presented with skin lesion in his left knee (May 2005). Excisional biopsy was consistent with a hematologic disease. Bone marrow and core biopsies were consistent with CML in chronic phase. Fluorescence in situ hybridization (FISH) revealed the presence of Ph-positivity in 95{\%} of the interphase nuclei evaluated. Treatment with imatinib was started. In October 2005, knee lesions recurred and biopsy was reported as acute myeloid leukemia (AML). In February 2006, cytogenetic analysis showed the presence of three clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),der(11)add(11)(p11.2) in 14 metaphases; 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),t(9;22)(q34;q11.2),add(11)(p11 .2) in 3 metaphases; and a normal diploid male karyotype in 3 metaphases. FISH confirmed the translocation of chromosome 11 materials to the short arm of one of the two chromosome 7 and demonstrated that 11.5{\%} of the interphase nuclei were positive for translocation (BCR/ABL1 rearrangement). Bone marrow analysis revealed a BCR-ABL1/ABL1 ratio of 15.26{\%}. New skin lesions in the upper arm appeared, which was negative for BCR-ABL1 rearrangement. Treatment with Tasigna was commenced.Indications:1 patient with Philadelphia chromosome negative chronic myeloid leukemia.Patients:One 73-year-old male patient.TypeofStudy:This case report described the outcome of Tasigna therapy in a patient with cutaneous Philadelphia-chromosome (Ph) negative chronic myeloid leukemia (CML) lesions. Letter to the Editor.",
author = "A. Quint{\'a}s-Cardama and H. Kantarjian and Abruzzo, {L. V.} and J. Cortes",
year = "2007",
month = "11",
doi = "10.1038/sj.leu.2404865",
language = "English (US)",
volume = "21",
pages = "2394--2396",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy [17]

AU - Quintás-Cardama, A.

AU - Kantarjian, H.

AU - Abruzzo, L. V.

AU - Cortes, J.

PY - 2007/11

Y1 - 2007/11

N2 - AuthorsConclusions:The present case illustrates the increasing recognition of cytogenetic abnormalities in Ph-negative cells in patients with CML treated with TKIs [tyrosine kinase inhibitors], and their association with progression to MDS [myelodysplastic syndrome] or AML. Moreover, it suggests that these abnormalities are not exclusively limited to the bone marrow and underscores the importance of close cytogenetic monitoring of these patients, to allow for an early detection of these rare aberrancies.DosageDuration:400 mg bid (=800 mg daily) orally. Duration: 8 weeks.Results:Over the next 8 weeks of Tasigna therapy, new nodular skin lesions appeared on his arms, back, legs, and abdomen. Bone marrow biopsy revealed 6% blasts, which were consistent with CML in chronic phase. Cytogenetic evaluation showed two clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)q(35),add(11)add(11)(p11.2) in 17 metaphases and a normal diploid male karyotype in 3 metaphases. BCR-ABL/ABL1 ratio in the peripheral blood decreased to 2.90%. Immunohistochemical analysis of a biopsied material from the inner thigh showed blasts cells positive for CD68 and negative for myeloperoxidase, CD117, and CD34, which was similar to his previous skin biopsy. FISH revealed no BCR-ABL1 rearrangement, but showed either deletion of an ABL1 gene or monosomy 9. Tasigna therapy was discontinued and systemic chemotherapy for induction of AML remission was instituted.AdverseEffects:No adverse events were mentioned.FreeText:The patient presented with skin lesion in his left knee (May 2005). Excisional biopsy was consistent with a hematologic disease. Bone marrow and core biopsies were consistent with CML in chronic phase. Fluorescence in situ hybridization (FISH) revealed the presence of Ph-positivity in 95% of the interphase nuclei evaluated. Treatment with imatinib was started. In October 2005, knee lesions recurred and biopsy was reported as acute myeloid leukemia (AML). In February 2006, cytogenetic analysis showed the presence of three clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),der(11)add(11)(p11.2) in 14 metaphases; 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),t(9;22)(q34;q11.2),add(11)(p11 .2) in 3 metaphases; and a normal diploid male karyotype in 3 metaphases. FISH confirmed the translocation of chromosome 11 materials to the short arm of one of the two chromosome 7 and demonstrated that 11.5% of the interphase nuclei were positive for translocation (BCR/ABL1 rearrangement). Bone marrow analysis revealed a BCR-ABL1/ABL1 ratio of 15.26%. New skin lesions in the upper arm appeared, which was negative for BCR-ABL1 rearrangement. Treatment with Tasigna was commenced.Indications:1 patient with Philadelphia chromosome negative chronic myeloid leukemia.Patients:One 73-year-old male patient.TypeofStudy:This case report described the outcome of Tasigna therapy in a patient with cutaneous Philadelphia-chromosome (Ph) negative chronic myeloid leukemia (CML) lesions. Letter to the Editor.

AB - AuthorsConclusions:The present case illustrates the increasing recognition of cytogenetic abnormalities in Ph-negative cells in patients with CML treated with TKIs [tyrosine kinase inhibitors], and their association with progression to MDS [myelodysplastic syndrome] or AML. Moreover, it suggests that these abnormalities are not exclusively limited to the bone marrow and underscores the importance of close cytogenetic monitoring of these patients, to allow for an early detection of these rare aberrancies.DosageDuration:400 mg bid (=800 mg daily) orally. Duration: 8 weeks.Results:Over the next 8 weeks of Tasigna therapy, new nodular skin lesions appeared on his arms, back, legs, and abdomen. Bone marrow biopsy revealed 6% blasts, which were consistent with CML in chronic phase. Cytogenetic evaluation showed two clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)q(35),add(11)add(11)(p11.2) in 17 metaphases and a normal diploid male karyotype in 3 metaphases. BCR-ABL/ABL1 ratio in the peripheral blood decreased to 2.90%. Immunohistochemical analysis of a biopsied material from the inner thigh showed blasts cells positive for CD68 and negative for myeloperoxidase, CD117, and CD34, which was similar to his previous skin biopsy. FISH revealed no BCR-ABL1 rearrangement, but showed either deletion of an ABL1 gene or monosomy 9. Tasigna therapy was discontinued and systemic chemotherapy for induction of AML remission was instituted.AdverseEffects:No adverse events were mentioned.FreeText:The patient presented with skin lesion in his left knee (May 2005). Excisional biopsy was consistent with a hematologic disease. Bone marrow and core biopsies were consistent with CML in chronic phase. Fluorescence in situ hybridization (FISH) revealed the presence of Ph-positivity in 95% of the interphase nuclei evaluated. Treatment with imatinib was started. In October 2005, knee lesions recurred and biopsy was reported as acute myeloid leukemia (AML). In February 2006, cytogenetic analysis showed the presence of three clones: 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),der(11)add(11)(p11.2) in 14 metaphases; 46,XY,der(7)t(7;11)(p12;p11.2)add(7)(q35),t(9;22)(q34;q11.2),add(11)(p11 .2) in 3 metaphases; and a normal diploid male karyotype in 3 metaphases. FISH confirmed the translocation of chromosome 11 materials to the short arm of one of the two chromosome 7 and demonstrated that 11.5% of the interphase nuclei were positive for translocation (BCR/ABL1 rearrangement). Bone marrow analysis revealed a BCR-ABL1/ABL1 ratio of 15.26%. New skin lesions in the upper arm appeared, which was negative for BCR-ABL1 rearrangement. Treatment with Tasigna was commenced.Indications:1 patient with Philadelphia chromosome negative chronic myeloid leukemia.Patients:One 73-year-old male patient.TypeofStudy:This case report described the outcome of Tasigna therapy in a patient with cutaneous Philadelphia-chromosome (Ph) negative chronic myeloid leukemia (CML) lesions. Letter to the Editor.

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