Nilotinib treatment induced large granular lymphocyte expansion and maintenance of longitudinal remission in a Philadelphia chromosome-positive acute lymphoblastic leukemia
It is well known that the second-generation tyrosine kinase inhibitor dasatinib evokes an immunological reaction as an off-target effect and induces large granular lymphocytes (LGLs) expansion in 30% of patients. However, LGLs expansion in nilotinib-treated patients is rare. We report the case of a...
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| Published in | International Journal of Hematology Vol. 111; no. 5; pp. 719 - 723 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Singapore
Springer Science and Business Media LLC
01.05.2020
Springer Singapore Springer Nature B.V |
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| Abstract | It is well known that the second-generation tyrosine kinase inhibitor dasatinib evokes an immunological reaction as an off-target effect and induces large granular lymphocytes (LGLs) expansion in 30% of patients. However, LGLs expansion in nilotinib-treated patients is rare. We report the case of a 65-year-old patient with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) who showed LGLs expansion during nilotinib treatment. The patient achieved complete remission (CR) after multi-agent chemotherapy combined with dasatinib treatment. However, ALL relapsed in the central nervous system and bone marrow when treatment was interrupted due to interstitial pneumonia. Nilotinib treatment was subsequently started and the patient achieved second CR. Marked peripheral blood lymphocytosis emerged after the start of nilotinib treatment. CD8 + CD57 + cytotoxic T cells were predominantly expanded and showed strong cytocidal activity against K562 Ph-positive leukemia cells. These results suggest that similar to dasatinib, nilotinib can induce LGLs expansion, possibly contributing to long-term remission in patients with Ph-ALL. |
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| AbstractList | It is well known that the second-generation tyrosine kinase inhibitor dasatinib evokes an immunological reaction as an off-target effect and induces large granular lymphocytes (LGLs) expansion in 30% of patients. However, LGLs expansion in nilotinib-treated patients is rare. We report the case of a 65-year-old patient with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) who showed LGLs expansion during nilotinib treatment. The patient achieved complete remission (CR) after multi-agent chemotherapy combined with dasatinib treatment. However, ALL relapsed in the central nervous system and bone marrow when treatment was interrupted due to interstitial pneumonia. Nilotinib treatment was subsequently started and the patient achieved second CR. Marked peripheral blood lymphocytosis emerged after the start of nilotinib treatment. CD8 + CD57 + cytotoxic T cells were predominantly expanded and showed strong cytocidal activity against K562 Ph-positive leukemia cells. These results suggest that similar to dasatinib, nilotinib can induce LGLs expansion, possibly contributing to long-term remission in patients with Ph-ALL. It is well known that the second-generation tyrosine kinase inhibitor dasatinib evokes an immunological reaction as an off-target effect and induces large granular lymphocytes (LGLs) expansion in 30% of patients. However, LGLs expansion in nilotinib-treated patients is rare. We report the case of a 65-year-old patient with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) who showed LGLs expansion during nilotinib treatment. The patient achieved complete remission (CR) after multi-agent chemotherapy combined with dasatinib treatment. However, ALL relapsed in the central nervous system and bone marrow when treatment was interrupted due to interstitial pneumonia. Nilotinib treatment was subsequently started and the patient achieved second CR. Marked peripheral blood lymphocytosis emerged after the start of nilotinib treatment. CD8 + CD57 + cytotoxic T cells were predominantly expanded and showed strong cytocidal activity against K562 Ph-positive leukemia cells. These results suggest that similar to dasatinib, nilotinib can induce LGLs expansion, possibly contributing to long-term remission in patients with Ph-ALL.It is well known that the second-generation tyrosine kinase inhibitor dasatinib evokes an immunological reaction as an off-target effect and induces large granular lymphocytes (LGLs) expansion in 30% of patients. However, LGLs expansion in nilotinib-treated patients is rare. We report the case of a 65-year-old patient with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) who showed LGLs expansion during nilotinib treatment. The patient achieved complete remission (CR) after multi-agent chemotherapy combined with dasatinib treatment. However, ALL relapsed in the central nervous system and bone marrow when treatment was interrupted due to interstitial pneumonia. Nilotinib treatment was subsequently started and the patient achieved second CR. Marked peripheral blood lymphocytosis emerged after the start of nilotinib treatment. CD8 + CD57 + cytotoxic T cells were predominantly expanded and showed strong cytocidal activity against K562 Ph-positive leukemia cells. These results suggest that similar to dasatinib, nilotinib can induce LGLs expansion, possibly contributing to long-term remission in patients with Ph-ALL. |
| Author | Morihiro Inoue Masao Hagihara Tomoyuki Uchida Shiro Ide Jian Hua Tomoiku Takaku Shin Ohara |
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| BackLink | https://cir.nii.ac.jp/crid/1870020692711258240$$DView record in CiNii https://www.ncbi.nlm.nih.gov/pubmed/31894532$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.3109/10428194.2013.842984 10.1016/j.leukres.2013.11.016 10.1056/NEJMoa055104 10.1002/cncr.25351 10.1182/blood-2002-07-2103 10.3109/10428194.2010.550074 10.1111/j.1365-2141.2009.07666.x 10.1056/NEJMoa1609324 10.1038/leu.2011.135 10.1111/j.1365-2141.2008.07433.x 10.3109/10428194.2012.695779 10.1038/leu.2012.348 10.1002/ajh.24926 10.1182/blood-2009-12-256800 10.1111/j.1582-4934.2009.00500_1.x 10.1007/s12185-010-0565-1 10.3324/haematol.13151 10.1006/meth.1996.0037 10.1182/blood-2015-03-636548 10.1038/leu.2009.46 10.3109/10428194.2011.647017 10.1007/s12185-009-0327-0 10.1007/s12185-018-2517-0 |
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| SubjectTerms | Acute lymphoblastic leukemia Aged Antineoplastic Combined Chemotherapy Protocols Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bone marrow Case Report CD57 antigen CD57 Antigens CD8 antigen CD8-Positive T-Lymphocytes CD8-Positive T-Lymphocytes - immunology Central nervous system Chemotherapy Chromosomes Cytotoxicity Dasatinib Enzyme inhibitors Expansion Hematology Humans Immunology Inhibitor drugs Kinases Leukemia Lymphatic leukemia Lymphocytes Lymphocytes - immunology Lymphocytes T Lymphocytosis Medicine Medicine & Public Health Multiagent systems Neoplasm Recurrence, Local Oncology Patients Peripheral blood Philadelphia Chromosome Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology Protein-tyrosine kinase Pyrimidines Pyrimidines - administration & dosage Remission Remission (Medicine) Remission Induction Targeted cancer therapy Time Factors Treatment Outcome Tyrosine |
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| Title | Nilotinib treatment induced large granular lymphocyte expansion and maintenance of longitudinal remission in a Philadelphia chromosome-positive acute lymphoblastic leukemia |
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