Sorafenib has been used in acute myeloid leukemias with FLT3-ITD mutation improving the outcomes. However the high incidence of treatment - emergent adverse event may be associated with treatment using sorafenib with cytotoxic chemotherapy. We have reported a case of severe thyroiditis in patient with a relapse of acute myelomonocytic leukemia.

Azacytidine and/or decitabine (DAC) were dramatically improved the prognosis of MDS and AML. Whereas, these drugs can be administered intravenously or subcutaneously, therefore the patients must visit a hospital every day. Aims: OR21 is a novel and potentially oral absorbable DAC prodrug. Actually, direct duodenal administration of OR21 successfully absorbed in cynomolgus monkey model. In this study, we investigated the efficacy of OR21 in MDS (MDS-L), AML cell lines (HL60, THP1, KG1a, Kasumi-1). Methods: OR21 was provided from Ohara pharmaceutical Co. MDS-L was kindly provided from Kaoru Tohyama and other cell lines were purchased from ATCC. Results: OR21 and DAC reduced DNMT protein levels and LINE-1 methylation levels in MDS and AML cell lines, using western blotting and pyrosequencing (cont, 88.9%; OR21, 74.2%; DAC, 75.2%; P < 0.05), respectively. OR21 and DAC induces cell growth inhibition and cell apoptosis in a dose dependent manner against MDS and AML. MDS and AML are characterized by hematopoietic stem cell disorder with impairment of cell differentiation. Induction of cell differentiation can be one of the therapeutic targets for MDS and AML. Up-regulated CD11b expression level was observed in OR21 or DAC treated MDS-L (cont, 17.8%; OR21, 72.0%, DAC, 70.1%; P < 0.05) and HL60 (cont, 7.1%; OR21, 42.0%; DAC, 64.2%; P < 0.05), corresponding to up-regulated CEBPE mRNA level (OR21, 14.9 fold; DAC, 21.9 fold in MDSL; OR21, 2.5 fold; DAC, 3.0 fold in HL60) which is a key late differentiation driver. These results indicate OR21 and DAC can induce cell differentiation via up-regulation of CEBPE. OR21 and DAC also upregulated tumor suppressor X (not shown) modulated proteasome pathway, inducing cell apoptosis. Finally, we used a mouse xenograft model to evaluate anti-tumor effect of OR21 in vivo. BALB/c Rag-2/JAK3 double-deficient (BRJ) mice were injected intravenously via tail vein with 5 × 10 6 HL60 cells. OR21, DAC and vehicle were administered by intraperitoneal injection at a dose of 2.7 mg/kg (OR21), 1.0 mg/kg (DAC) and 1% DMSO (vehicle) twice weekly; OR21 and DAC were equal in AUC (OR21 is readily degradation with gastric acid in mouse). Significant decreased leukemic cells in peripheral blood at 37 days (Vehicle, 2.96%; OR21, 0.75%; P = 0.049) and increased CD11b positive cells (Vehicle, 40.9%; OR21, 60.0%) was observed in OR21 treated mice. OR21 significantly prolonged survival (median survival 49 days and 44 days, P = 0.005), while DAC did not (median 46.5 days and 44 days, P = 0.164) and decreased LINE-1 methylation levels (Vehicle, 83.7%; OR21, 62.8%; P < 0.0001) were observed in OR treated mouse in bone marrow. Interestingly, OR21 treated mouse tended to be less involved in anemia than DAC treated mouse (hemoglobin; Vehicle, 17.5 g/dL; OR21, 17.1 g/dL; DAC, 15.8 g/dL). Summary/Conclusion: OR21 has anti-tumor effect agaisnt MDS and AML via cell differentiation and apoptosis induced by up-regulation of CEBPE and tumor suppressor X. OR21 has safer profile and oral absorbability than DAC, thus OR21 can b...

Background:Early mortality (EM) in multiple myeloma (MM) ranges from 4% to 25% mostly depending on the patients included and on treatment options. EM tends to be lower in clinical trials including younger, transplant‐eligible patients or in bortezomib‐ and lenalidomide‐based regimens in comparison with elderly patients and conventional chemotherapy treatment.Aims:To estimate risk factors associated with EM in patients with newly diagnosed MM.MethodsPatients with newly diagnosed MM were included into the study (from Jan 2013 to Feb 2019). EM was defined if it occurred within 1 year of entry into the study. Adverse cytogenetic abnormalities were specified as gain(1q), t(4;14), t(14;16), t(14;20) or del(17p).Results:A total of 174 patients with newly diagnosed MM (82 male, 92 female; median age 61 years) were involved in the study. Follow‐up period was 1‐71.4 months (median 8 months). The majority of patients developed an advanced stage of disease (Duriе‐Salmon stage 3–141 (81.1%), ISS stage 3–99 (56.9%)). All patients received chemotherapy regimens containing proteasome inhibitors as first‐line therapy and immunomodulatory drugs, intensive and conventional chemotherapy regimens as second‐ or next‐line therapy. During follow‐up period fatal outcome was observed in 45 (25.9%) of 174 patients, of them 16 (9.2%) patients with EM. Median early mortality was 4.7 months. The age of patients with EM and patients survived > 1 year was comparable (median age 64.5 vs. 61, respectively). A larger proportion of patients with EM had Durie‐Salmon stage 3 (93.8% vs 79.7%), ISS stage 3 (75.0% vs 55.1%). Fish in situ hybridization analysis was conducted in 126 (72.4%) patients, adverse cytogenetic abnormalities were present in 4/8 (50.0%) patients with EM and 33/118 (27.9%) patients survived >1 year. Risk factors assotiated with EM were ECOG performance status ≥ 3 score (87.5% vs 40.5%, p = 0.0003), C‐reactive protein level > 10 mg/L (62.5% vs 26.6%, p = 0.007), high lactic acid dehydrogenase activity (81.3% vs 46.2%, p = 0.008), platelet count < 150 × 109/L (43.8% vs 18.9%, p = 0.047) (tab.). For the 16 patients with EM, 11 (68.8%) of deaths were related to MM progression, 4 (25.0%) were due to infections and 1 (6.2%) ‐ heart failure.Summary/Conclusion:EM in patients with newly diagnosed MM was 9.2%. Risk factors associated with EM were poor performance status, elevated serum LDH activity, low platelet count, high serum C‐reactive protein.image

Background: In the era of novel anti-myeloma agents and monoclonal antibodies (daratumumab) and due to their high cost, earlier low cost regimens (VAD or CyBorD) may be used. Aims: to compare outcome of treatment of CyBorD versus VAD regimens in multiple myeloma Methods: This cohort study included 89 MM patients treated at National Cancer Institute (NCI), Cairo, Egypt from January 2011 to December 2015. All patients were evaluated clinically and laboratory for different responses with either lines of treatment (VAD versus CyBorD), and correlated with different survival parameters; progression free (PFS), disease free (DFS), and overall survival (OS), and clinico-pathologic factors. Results: The median age of patients was 54 years (32-76), with male predominance (male to female ratio 1.87:1). The most common presenting symptoms were bony pains (44.9%) followed by bony masses (22.5%), fractures

Imaging of bone lesions has an important role in diagnosis of multiple myeloma (MM) and evaluating the response to treatment. Computed tomography scan (CT) allows to detect osteolysis, plasmacytoma and the risk of fractures with high sensitivity. In the National Research Center For Hematologysince 2014 all patients with MM are diagnosed with the whole-body low-dose CT.The aim of the study was to demonstrate the sensitivity of the whole-body low-dose CT and to characterize localization, number and size of bone lesions in primary MM patients.Materials and methods. 50 patients with newly diagnosed MM were enrolled in the study. The diagnosis was established in accordance with international diagnostic criteria. All patients received the whole-body low-dose CT. According to the Durie-Salmon and ISS staging systems 62% and 66% of patients had stage III, respectively.Results. 96% of MM patients had bone lesions. In 30% of patients, bone involvement was the only criterion for CRAB. Pelvic bone lesions was most often diagnosed (92%). The destruction of the long bones of the arms and legs were most rarely detected (42% of patients) and mostly small. The presence of intraosseous plasmocytoma was noted in 40% of cases.Conclusion. The whole-body low dose CT was found to be the most sensitive modality for detection osteolytic bone lesions. Low-dose CT is available in MM case with bone disease only, for establish symptomatic stage. This patients require immedate antimyeloma treatment.