Tyrosine kinase inhibitor therapy for acute myeloid leukemia with late-appearing Philadelphia chromosome

Aoki, Jun; Kakihana, Kazuhiko; Kobayashi, Takeshi; Hirashima, Yuka; Akiyama, Hideki; Ohashi, Kazuteru; Sakamaki, Hisashi

doi:10.1016/j.leukres.2011.10.008

Cited by 6 publications

(6 citation statements)

References 5 publications

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“…Of 33 patients with follow-up information available regarding the disease status, 30 had relapsed or refractory disease and 26 were dead at last follow-up, with a median follow-up of 5 months (range, 1-22 months). For the 16 patients with follow-up information available regarding the evolution of the Philadelphia chromosome-positive clones, the Philadelphia chromosome-positive clones were persistent and/or became the major clone in most patients despite intensive chemotherapy, and only 3 patients achieved cytogenetic remission [32,52,53]. The emergence of secondary Philadelphia chromosome can be explained by multiple mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Secondary Philadelphia chromosome acquired during therapy of acute leukemia and myelodysplastic syndrome

et al. 2018

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The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis. The diagnoses at initial presentation were acute myeloid leukemia (n = 11), myelodysplastic syndrome (n = 5), B lymphoblastic leukemia (n = 2), and T lymphoblastic leukemia (n = 1); no cases carried the Philadelphia chromosome. The Philadelphia chromosome was detected subsequently at relapse, or at refractory stage of acute leukemia or myelodysplastic syndrome. Of 14 patients evaluated for the BCR-ABL1 transcript subtype, 12 had the e1a2 transcript. In 11 of 14 patients, the diseases before and after emergence of the Philadelphia chromosome were clonally related by karyotype or shared gene mutations. Of 15 patients with treatment information available, 7 received chemotherapy alone, 5 received chemotherapy plus tyrosine kinase inhibitors, 2 received tyrosine kinase inhibitors only, and 1 patient was not treated. Twelve patients had follow-up after acquisition of the Philadelphia chromosome; all had persistent/refractory acute leukemia. Thirteen of 15 patients died a median of 3 months after the emergence of the Philadelphia chromosome. In summary, secondary Philadelphia chromosome acquired during therapy is rare, and is associated with the e1a2 transcript subtype, terminal disease stage, and poor outcome.

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Section: Discussionmentioning

confidence: 99%

Secondary Philadelphia chromosome acquired during therapy of acute leukemia and myelodysplastic syndrome

et al. 2018

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“…One patient achieved a CCyR, but died of a brain abscess, two patients had a transient response [73,76], and two patients had no response [66,75]. Interestingly, in three patients, the TKI treatment led to an eradication of the Ph-positive clone despite an overall refractory disease [65,74,77].…”

Section: Treatment Of Bcr-abl+ Amlmentioning

confidence: 96%

“…In 14 published cases, BCR-ABL was acquired upon AML relapse [11,55,[71][72][73][74][75][76][77]. In 7 of these 14 patients, the morphologic classification was given.…”

Section: ) Bcr-abl At Aml Relapsementioning

confidence: 99%

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

et al. 2016

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BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. In this study, we analyzed all published cases since 1975 as well as cases from our institution in order to present common clinical and molecular features of this rare disease. Our analysis shows that BCR-ABL predominantly occurs in AML-NOS, CBF leukemia, and AML with myelodysplasia-related changes. The most common BCR-ABL transcripts (p190 and p210) are nearly equally distributed. Based on the analysis of published data, we provide a clinical algorithm for the initial differential diagnosis of BCR-ABL+ AML. The prognosis of BCR-ABL+ AML seems to depend on the cytogenetic and/or molecular background rather than on BCR-ABL itself. A therapy with tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinib is reasonable, but-due to a lack of systematic clinical data-their use cannot be routinely recommended in first-line therapy. Beyond first-line treatment of AML, the use of TKI remains an individual decision, both in combination with intensive chemotherapy and/or as a bridge to allogeneic stem cell transplantation. In each single case, potential benefits have to be weighed against potential risks.

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“…Together with the elevated number of metaphases harboring the Philadelphia chromosome (15/15), these findings suggest that the two molecular aberrations were present within the same leukemic clone rather than occurring in two separate clones. However, in recently reported patients with Ph-positive AML, targeted treatment with TKIs was able to abrogate the BCR-ABL +ve clone but did not lead to complete hematologic response, indicating that the BCR-ABL lesion was present at the subclonal level [16]. This highlights the more complex clonal architecture of Ph-positive AMLs as compared to CML.…”

Section: Discussionmentioning

confidence: 99%

Acute Myeloid Leukemia with Concomitant BCR-ABL and NPM1 Mutations

Mariotti

Meconi

Palmieri

et al. 2019

Case Reports in Hematology

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We present a case report of a patient with acute myeloid leukemia (AML) characterized by the simultaneous presence of nucleophosmin 1 (NPM1) mutation and the breakpoint cluster region-Abelson (BCR-ABL) fusion oncogene. Our findings emphasize the importance of routinely including BCR-ABL in the diagnostic workup of AML in order to offer to the patients the most appropriate risk category and treatment options.

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Tyrosine kinase inhibitor therapy for acute myeloid leukemia with late-appearing Philadelphia chromosome

Cited by 6 publications

References 5 publications

Secondary Philadelphia chromosome acquired during therapy of acute leukemia and myelodysplastic syndrome

Secondary Philadelphia chromosome acquired during therapy of acute leukemia and myelodysplastic syndrome

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

Acute Myeloid Leukemia with Concomitant BCR-ABL and NPM1 Mutations

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