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Imatinib Mesylate-Induced Complete Cytogenetic Response in Acute Myeloid Leukemia with t(5;12)(q33;p13).
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| Zeitschriftentitel: | Blood |
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| Personen und Körperschaften: | , , , |
| In: | Blood, 108, 2006, 11, S. 4414-4414 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>Imatinib mesylate (IM) is a tyrosine kinase inhibitor (TKI) with established activity in chronic myelogenous leukemia (CML) due to targeted disruption of constitutively activated bcr-abl TK in the leukemic clone. IM also inhibits several other TKs that are aberrantly activated in other diseases such as c-kit in gastrointestinal stromal cell tumor, platelet-derived growth factor receptor-α (PDGFR-α) in hypereosinophilic syndrome, and PDGFR-β in chronic myelomonocytic leukemia (CMML). In CMML, PDGFR-β at 5q33 is typically fused with the ETV6 locus (formerly TEL) at 12p13 as t(5;12)(q33;p13). We report a case of IM-induced complete cytogenetic response in a patient with acute myeloid leukemia (AML) who presented with multiple extramedullary sites of disease and a complex karyotype of 49,XX,t(5;12)(q33;p13),+10,+11,+19. On transfer to our facility shortly after initial presentation, the patient had fatigue and cervical lymphadenopathy with a white blood cell count of 6,200/uL (43% segs, 36% lymphs, 9% monos, 11% eos, rare blasts) and was platelet transfusion dependent. She had no known prior history of CMML or myeloproliferative disorder, though she had increasing fatigue for 6 months. Excisional biopsy of a cervical node demonstrated a myeloid sarcoma; bone marrow biopsy confirmed AML, subtype M4 by FAB classification, with 31% blasts. There was mild eosinophilia in the marrow. The karyotype from the node was the same as in the marrow. CT scans demonstrated extensive lymphadenopathy (including neck, axilla, mediastinum, abdomen), splenomegaly measuring 15cm, and bilateral pleural effusions. After induction chemotherapy consisting of cytarabine, daunorubicin, etoposide, and tipifarnib (refused further tipifarnib after receiving only one dose) on an NCI-sponsored clinical trial, the patient had morphologic remission in the bone marrow but persistent t(5;12) in 20/20 cells as well as persistent lymphadenopathy, splenomegaly, and pleural effusions. The other cytogenetic abnormalities had resolved. Given prior reports of IM-responsive CMML in patients with t(5;12)(q33;p13), the patient began IM at 400mg daily. After one month of IM, repeat bone marrow biopsy demonstrated morphologic CR and only 6/20 cells with t(5;12). On the basis of this improvement, a clinical decision was made to postpone further cytotoxic chemotherapy-based consolidation and continue IM while an allogeneic stem cell donor could be identified. After 10 weeks of IM, bone marrow biopsy demonstrated continued CR with normal cytogenetics. Flouresence-in-situ-hybridization (FISH) with an ETV6 breakapart probe was also negative (probe was positive on the diagnostic sample in 66% of cells). The patient had complete resolution of the pleural effusions with no palpable adenopathy or splenomegaly and a performance status of 100%. Allogeneic transplantation in first remission was recommended due to the presence of multiple additional cytogenetic changes/ extramedullary disease at diagnosis and the availability of a 10/10 HLA allele matched donor. Molecular characterization of PDGFR-β transcript levels in this patient is ongoing. This case suggests that efficacy of IM in t(5;12) positive AML may be analogous to its efficacy in t(9;22) positive blast phase CML. Targeted inhibition of aberrantly activated PDGFR-β with IM may be effective in clearing residual disease in the marrow following cytotoxic chemotherapy for AML patients with t(5;12)(q33;p13). IM may also be a useful adjunct to cytotoxic treatment in AML patients with aberrant activation of other IM-sensitive TKs.</jats:p> |
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| Umfang: | 4414-4414 |
| ISSN: |
0006-4971
1528-0020 |
| DOI: | 10.1182/blood.v108.11.4414.4414 |