Simultaneous Supression of CML and GIST by Imatinib in Single Patient.
Authors: Mishima Yuko , Terui Yasuhito , Takeuchi Kengo , Yokoyama Masahiro , Nagasaki Eijiro , Fukunaga Tetsu , Yamamoto Junji , Yamaguchi Toshiharu , Mizunuma Nobuyuki , Kato Yo , Hatake Kiyohiko 
Published: April 2020

Abstract
Background: Imatinib mesylate, that is tyrosine kinase inhibitor, is highly effective drug for chronic myeloogenous leukemia(CML). Imatinib induces cytogenetical and molecular remission for CML without bone marrow transplantation. Imatinib is effective for not only CML but Gastrointestinal Tumor (GIST). Imatinib targets mutation of c-kit or platelet derived growth factor receptor alpha (PDGF-alpha) in GIST. Before these days, the case of double cancer of CML with GIST has not been reported yet.
Clinical Course: A 43-year-old man, who admitted our hospital, had leukocytosis, thrombocytosis, and melaena. His white blood cell (WBC) count was 65×10 4 /μL, hemoglobin level was 13.5 g/dl, and platelet count was 114.2×10 4/μL. The WBC fraction was as follows: blast 1%; promyelocyte 1.5%; myelocyte 13.5%; metamyelocyte 2.5%; band 5.5%; segment 46.5%; lymphocyte 16.5%; monocyte 4.5%; basophil 3.0% and eosinophil 5.5%. The bone marrow aspiration demonstrated the hypercellular bone marrow and blast cells did not increase and metaplasia of cells was not observed. Karyotypic FISH analysis revealed the chromosome of t(9;22)(q34:q11) and he was diagnosed as CML in chronic phase. He had no splenomegaly. At this time, gastric submucosal tumor was detected by endoscopy of the upper gastrointestinal tract. The tumor located lesser curvature of the mid-stomach and had no mobility. Under the fiberscopic ultrasonography, the submucosal tumor had low and heterogenous echogenic pattern. The computed tomography showed that the tumor, which size was six cm, was solid mass and associated with calcification. For the therapy, in the first, Imatinib (400mg) was started against CML. His WBC and platelet was slowly decreased and after four months he reached at morphological remission. FISH showed the presence of 30% bcr/abl+ transcript in his bone marrow. In this period, although the size of his submucosal tumor did not change on the CT, it seemed that the elevation of mucosa was decreased under the gastrointestinal fiberscopy. After nine months from start of Imatinib, he received surgical resection of gastric submucosal tumor. The size of removed tumor was about six cm and the tumor associated with broad necrotic lesion. Histological analysis indicated from limited alive lesion. Microscopically, fibrotic and hyalinized lesions cover approximately 99% of the area examined. The residual tumor consists of spindle cells with mild nuclear atypia. Immunohistochemically, the tumor is positive for KIT/CD117 and CD34, and negative for muscle specific actin (HHF35), smooth muscle actin (1A4), desmin and S100 protein. These features are characteristic of GIST. The c-kit mutation was studied by PCR. And we identified the tumor was gastrointestinal stromal tumor (GIST).
Discussion: That is first report of simultaneous occurrence CML and GIST in one patient. We selected that after the remission of CML with Imatinib, resection of GIST was performed. That was very curative therapy for him.