RESUMO
Our patient was diagnosed with chronic myeloid leukemia (CML) in chronic phase (CP) when he was 40 years old. Although dasatinib (DAS) was prescribed during his clinical course, he was poorly compliant with the treatment. In November 20XX, at 65 years of age, he visited our hospital with leukocytosis. He was diagnosed with CML in CP and recommenced DAS at 50 mg/day, achieving a complete hematological response after 2 months. However, DAS was increased to 100 mg/day because only minimum cytogenetic response was evident even after 9 months, but CML progressed to the accelerated phase after 18 months. The ABL kinase domain mutations T315I and F317L were detected. Ponatinib (PON) was not yet approved, and he declined allogeneic stem cell transplantation therapy. He commenced interferon-α (IFN-α) in addition to DAS, and the F317L mutation (only) disappeared after 7 months; the patient achieved a major cytogenetic response. In January 20XXï¼4, he commenced PON monotherapy (the drug was approved by this time) and achieved a major molecular response after 8 months. The T315I mutation disappeared during PON therapy. Although IFN-α is rarely used in the treatment of CML, this case suggests that IFN-α should be re-considered in patients with CML who exhibit tyrosine kinase inhibitor resistance.
Assuntos
Imidazóis/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Proteínas Oncogênicas v-abl/genética , Piridazinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Mutação , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
A 69-year-old man visited a doctor because of systemic lymphadenopathy. Peripheral blood examination revealed leukocytosis, anemia, and decreased platelet count (WBC, 103,060/µl; lymph, 92.2%; Hb, 8.9 g/dl; and Plt, 4.1×104/µl). Bone marrow biopsy revealed that approximately 70% of nucleated cells were small, mature lymphoid cells with positive immunostaining for CD5, CD20, and CD23. He was diagnosed with chronic lymphocytic leukemia (CLL). The IgH/CCND1 translocation and ATM locus loss in 20% and 95% peripheral cells, respectively, were detected by fluorescence in situ hybridization. Immunostaining revealed that cyclin D1 was positive in approximately 30% bone marrow cells. As the positive rate of CCND1 fusion signal was low, the diagnosis of mantle cell lymphoma was excluded. In contrast, signals of ATM locus deletion were detected in most tumor cells. Therefore, we assessed that IgH/CCND1 translocations occurred during the natural clinical course of CLL with ATM locus deletion from the onset of disease. The secondary IgH/CCND1 translocation in CLL is rare, and all reported cases with such translocations received treatments with alkylating agents. This is the first report regarding secondary IgH/CCND1 translocation during the natural clinical course of CLL and may provide insights into CLL pathogenesis.
Assuntos
Ciclina D1/genética , Cadeias Pesadas de Imunoglobulinas/genética , Leucemia Linfocítica Crônica de Células B/genética , Translocação Genética , Idoso , Humanos , Hibridização In Situ , MasculinoRESUMO
A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue, and weakness. He was eventually diagnosed with dengue virus infection, detected using reverse transcription polymerase chain reaction for the genome and by the presence of nonstructural protein 1 in his peripheral blood. Symptomatic treatments such as acetaminophen for the fever were not effective. Moreover, peripheral blood examination showed drastically decreased white blood cells and platelets, as well as marked elevations of ferritin and soluble interleukin 2 receptor. Furthermore, bone marrow examination revealed increased macrophages with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis (HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days dramatically reduced his temperature, thereby ameliorating physical symptoms and restoring normal peripheral blood data. He was discharged 12 days after admission. Dengue infection with HLH is rare and this is the first report, to our knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy may be effective in such cases.
Assuntos
Dengue/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Esteroides/uso terapêutico , Adulto , Biópsia , Dengue/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Prevenção SecundáriaRESUMO
A 64-year-old man was diagnosed with limited cutaneous systemic sclerosis 5 years prior to this report. His sclerotic skin symptoms did not respond to oral low-dose prednisone (5-10 mg/day). Five years after the diagnosis, the patient presented with leukocytosis 3.8 × 109/L in a routine blood test, and was finally diagnosed with chronic-phase chronic myelogenous leukemia (CML). The leukemia responded optimally to initial dasatinib, and a complete cytogenetic response was achieved after 6 months of therapy. His skin symptoms dramatically improved in parallel with dasatinib therapy, as indicated by a decrease in the modified Rodnan skin score, from 12 points at diagnosis to 2 after 9 months. It has been reported that imatinib, a first-generation tyrosine kinase inhibitor, improves skin sclerosis in some patients with systemic sclerosis. To the best of our knowledge, this is the first report of simultaneous improvement of CML and limited cutaneous systemic sclerosis in response to dasatinib. Further study of the mechanism of action of dasatinib is crucial.