ABSTRACT
Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow, and often associated with autoimmune disorders. According to the current WHO classification of the hematopoietic and lymphoid tissue tumors, the clonal LGL expansions are further classified as T-cell large granular lymphocytic leukemia (T-LGLL), chronic lymphoproliferative disorders of NK cells (CLPD-NK) and aggressive NK cell leukemia. Since there is a general lack of awareness of this disease, some patients may be misdiagnosed or some cases may be missed when diagnosis was done. At present, the pathogenesis of LGLL remains incomplete and unclear, and the therapeutic effects are unsatisfactory. For this reason, it is necessary to find prognostic marks and therapeutic targets of this disease. The constitutive activation of JAK/STAT pathway has been claimed to be involved in the development of LGLL. Recently, the somatic mutations in the SH2 domain of STAT3 in LGLL are frequently observed, which lead to the activation of JAK/STAT pathway. STAT3 is the first molecular markers that are highly specific for LGLL, and STAT3 mutations have been rarely detected in other tumor types studied, thus the STAT3 mutations can be used as molecular markers for LGLL diagnosis and can provide a novel therapeutic target for patients with LGLL.
Subject(s)
Humans , Janus Kinases , Genetics , Metabolism , Leukemia, Large Granular Lymphocytic , Genetics , Metabolism , Mutation , STAT3 Transcription Factor , Genetics , Metabolism , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To compare the efficacy and safety of BD regimen combined with cyclophosphamide(CTX) and pirarubicin chemotherapy(P-CAD) for patients with relapse/refractory multiple myeloma(MM).</p><p><b>METHODS</b>Twenty-eight cases of relapse/refractory MM were enrolled in a group of P-CAD regimen, 36 cases of relapse/retractory MM treated with BD were used as controls. The therapeutic efficacy and adverse reactions of 2 regimens for patients with relapse/retractory MM were compared and analyzed.</p><p><b>RESULTS</b>The overall response rate (CR+NCR+PR+MR) of the 28 cases treated with P-CAD regimen was 85.7%, and the response rate (CR+PR) was 75.0%. The median progression-free survival time were 16.1 months, and the average survival time were 30.6 months, while the overall response rate of the 36 patients treated with BD regimen was 63.9%, and the response rate was 55.6%. The median progression-free survival time were 13.7 months, and the average survival time were 26.7 months. The adverse reactions of 2 groups included gastrointestinal reactions, peripheral neuropathy, fatigue, skin rashes, leucopenia and thrombocytopenia, and they were all well tolerated.</p><p><b>CONCLUSION</b>BD regimen combined with cyclophosphamide and pirarubicin chemotherapy can improve the response rate of patients with relapse/refractory multiple myeloma, and shows the trend of prolonging PFS and survival times. Patients were well tolerated, and this regimen is a new choice in treatment of relapse/refractory MM.</p>