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Restoration of donor chimerism by nilotinib in a chronic myeloid leukaemia patient post mutation-associated imatinib mesylate resistance and allogeneic stem cell transplant failure

Bone Marrow Transplantation volume 42, pages 833–835 (2008)Cite this article

Chronic myeloid leukaemia is a haematopoietic stem cell malignancy characterized by the p210 BCR-ABL1/ABL1 oncoprotein. Treatment for CML and a subset of ALL patients has been revolutionized by the advent of imatinib mesylate,1 a tyrosine kinase inhibitor, which replaced IFN-α and haematopoietic stem cell transplant (SCT) as front-line therapy.2 DNA mutations in the BCR-ABL1 kinase domain, to which imatinib mesylate binds, may result in the loss of imatinib mesylate binding and drug resistance.3 Second-generation TKIs, dasatinib and nilotinib, retain binding in the presence of the majority of BCR-ABL1 kinase domain mutations because of improved topological fit to the enzyme4, 5and show promise in the treatment of patients with resistant disease.6, 7

A 48-year-old male patient presented with fatigue and weight loss. Physical examination revealed splenomegaly of 7 cm. Initial laboratory evaluation revealed haemoglobin 10.6 g/100 ml, WBC 238 × 109/l and platelet count 445 × 109/l. Morphological analysis of the bone marrow revealed CML in chronic phase. Cytogenetic analysis showed 100% Philadelphia (Ph)-positive metaphases, FISH confirmed the p210 translocation and the presence of the BCR-ABL1 fusion gene was demonstrated using RQ-PCR; BCR-ABL1/ABL1 ratio was 56.9%, which was consistent with the diagnosis of CML.

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Acknowledgements

We thank Peig Carroll and Nicola Gardiner for their help in obtaining patient details.

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Authors and Affiliations

  1. Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland

    L M O'Connor & S R McCann

  2. Cancer Molecular Diagnostics Laboratory, St James's Hospital, Dublin, Ireland

    S Langabeer

  3. Department of Haematology, St James's Hospital, Dublin, Ireland

    S R McCann & E Conneally

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  1. L M O'Connor
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  2. S Langabeer
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  4. E Conneally
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Correspondence to L M O'Connor.

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O'Connor, L., Langabeer, S., McCann, S. et al. Restoration of donor chimerism by nilotinib in a chronic myeloid leukaemia patient post mutation-associated imatinib mesylate resistance and allogeneic stem cell transplant failure. Bone Marrow Transplant 42, 833–835 (2008). https://doi.org/10.1038/bmt.2008.250

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