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Clonal expansion of...
Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
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Mustjoki, S. (author)
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- Ekblom, Marja (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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Arstila, T. P. (author)
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Dybedal, I. (author)
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Epling-Burnette, P. K. (author)
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Guilhot, F. (author)
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Hjorth-Hansen, H. (author)
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- Hoglund, M. (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Hematologi
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Kovanen, P. (author)
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Laurinolli, T. (author)
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Liesveld, J. (author)
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Paquette, R. (author)
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Pinilla-Ibarz, J. (author)
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Rauhala, A. (author)
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Shah, N. (author)
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- Simonsson, Bengt (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Hematologi
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Sinisalo, M. (author)
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Steegmann, J. L. (author)
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- Stenke, L. (author)
- Karolinska Institutet
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Porkka, K. (author)
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(creator_code:org_t)
- 2009-03-19
- 2009
- English.
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:8, s. 1398-1405
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Abstract
Subject headings
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- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. Leukemia (2009) 23, 1398-1405; doi:10.1038/leu.2009.46; published online 19 March 2009
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Ph plus leukemia
- TKI therapy
- immunomodulation
- dasatinib
- MEDICINE
Publication and Content Type
- art (subject category)
- ref (subject category)
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Leukemia
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To the university's database
- By the author/editor
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Mustjoki, S.
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Ekblom, Marja
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Arstila, T. P.
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Dybedal, I.
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Epling-Burnette, ...
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Guilhot, F.
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show more...
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Hjorth-Hansen, H ...
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Hoglund, M.
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Kovanen, P.
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Laurinolli, T.
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Liesveld, J.
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Paquette, R.
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Pinilla-Ibarz, J ...
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Rauhala, A.
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Shah, N.
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Simonsson, Bengt
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Sinisalo, M.
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Steegmann, J. L.
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Stenke, L.
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Porkka, K.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Leukemia
- By the university
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Lund University
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Uppsala University
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Karolinska Institutet