Objective:To compare the clinical characteristics and outcomes of patients newly diagnosed with multiple myeloma(NDMM)with bone-related extramedullary(EM-B)disease and those with extraosseous extramedullary(EM-E)disease and to address their prognostic factors.Methods:The clinical features, outcomes, and prognostic factors were retrospectively analyzed in 80 patients with NDMM with extramedullary disease.Results:Among 80 patients with extramedullary disease, 51 had EM-B and 29 EM-E. The level of β 2-microglobulin(5.82 mg/L vs 3.99 mg/L, P=0.030), lactate dehydrogenase(256 U/L vs 184 U/L, P=0.003), 1q21 amplification rate(78.6% vs 53.1%, P=0.035), and Ki-67 proliferation index(50% vs 25%, P=0.002)in the EME group were significantly higher than those in the EM-B group. The posieive rate of CD56(14.3% vs 66.7%)and overall response rate(60% vs 82.3%)in EM-E group were significantly lower than those in EM-B group. The median overall survival (OS)of patients with EM-E and EM-B was 14.5 and 49.5 months, and the median progression-free survival(PFS)of the two groups was 9.0 and 18.0 months. Patients with EM-E had a significantly shorter OS( P=0.035)and PFS( P < 0.001)than those of patients with EM-B, whereas the PFS did not significantly differ( P=0.263)when patients accepted proteasome inhibitor(PI)-based regimens for induction therapy. Multivariate analysis with Cox model showed the best response that did not achieve partial response(PR)was an independent poor prognostic factor for both OS and PFS in NDMM patients with EM-E( P=0.031, P=0.005), ISS-III, and the best response that did not achieve PR were independent prognostic factors for the shorter OS in patients with NDMM with EM-B( P=0.009, P=0.044). Conclusions:The clinical characteristics and outcomes of patients with NDMM with EM-E are different from patients with EM-B. Outcomes of patients with EM-E is significantly poor. PI induction therapy improved the PFS of patients with EM-E.

Objective:Endoplasmic reticulum stress(ERS)was used as the research emphasis to further investigate the mechanisms of apoptosis of FLT3-ITD-mutated leukemia cells and decreased expression of FLT3-ITD mutated protein induced by all-trans retinoic acid(ATRA).Methods:FLT3-ITD-mutated leukemia cell lines(MV4-11 and MOLM13)were treated with ATRA. Flow cytometry was conducted to assess cell apoptosis. Real-time fluorescent quantitative PCR(RT-qPCR)and Western blot were used to detect the expression of ERS-related and autophagy-related genes and protein, respectively.Results:A low-dose ATRA further increased FLT3-ITD cells and ERS levels. ATRA acted on the ERS-related PERK/eif2ɑ signaling pathway and continued to increase the ERS of FLT3-ITD cells, resulting in an upregulation of apoptotic gene CHOP expression. After the treatment with ATRA, FLT3-ITD protein in FLT3-ITD cells was decreased. Of the two main ERS-related protein degradation pathways, ER-associated degradation(ERAD)and ER-activated autophagy(ERAA), the expression of ERAD-related protein ATF6 in FLT3-ITD cells was not significantly changed on ATRA, whereas the expression of ERAA-related proteins Atg7 and Atg5 were significantly increased.Conclusions:ATRA further raises the ERS level of FLT3-ITD cells continuously by activating the ERS-related PERK/eif2ɑ signal pathway and induces FLT3-ITD protein autophagy degradation through ERAA pathway, which induces apoptosis of FLT3-ITD-mutated leukemia cells. These results provide preliminary evidence on the use of ATRA in the treatment of refractory leukemia with FLT3-ITD.

Objective: To explore the clinical features of patients with synchronous lymphoma and carcinoma. Methods: The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively. Results: Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence. Conclusion The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.

Objective:To evaluate the efficacy and safety of combination therapy of eltrombopag, recombinant human thrombopoietin (rhTPO) , and standard immunosuppressive therapy (IST) for severe aplastic anemia (SAA) .Methods:A total of 16 cases with SAA treated with IST combined with eltrombopag and rhTPO were retrospectively analyzed.Results:At 3 months, the total response rate was 81.3%, and the complete hematological response rate was 37.5%. At 6 months, the total response rate was 87.5%, and the complete hematological response rate was 50.0%. The median time of platelet transfusion independence was 35 (16-78) days, the median time of red blood cell transfusion independence was 47.5 (15-105) days, the median platelet transfusion was 5.5 (3-20) U, and the median red blood cell transfusion was 6.5 (2-16) U.Conclusion:The combination of eltrombopag and rhTPO can improve the hematological response rate of IST for SAA and the quality of hematological remission with minimal toxic effects.