Several clinical trials of bone marrow cell infusion in patients with liver cirrhosis (LC) have shown clinical improvement, despite conflicting results from animal models. We investigated serial pathological features and the clinical impact after autologous bone marrow infusion (ABMI) in patients with advanced LC. Ten patients with advanced LC due to chronic hepatitis B virus infection underwent ABMI. Serological tests, MRI, and liver biopsies were performed, and quality of life was assessed by a questionnaire. Median serum albumin and hemoglobin levels increased significantly after ABMI. All patients showed an improvement in quality of life, with no serious adverse events. Liver volume, measured by MRI, increased in 80% of the patients, and ascites decreased after ABMI. Child-Pugh scores were also significantly improved at 6 months after ABMI. In the serially biopsied livers, a gradually increasing activation of the hepatic progenitor cell (HPC) compartment, including HPC activation (ductular reaction) and HPC differentiation (intermediate hepatocyte), reached a peak after 3 months, with continued proliferation of hepatocytes, and returned to baseline levels after 6 months. There was no significant change in grade or stage of liver fibrosis or stellate cell activation after ABMI. ABMI is suggested to improve liver function and to activate the progenitor cell compartment. Although clinical improvement was sustained for more than 6 months, histological changes in the liver returned to baseline 6 months after ABMI. Further comparative studies are warranted.

The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression. We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples. Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders. This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. clinicaltrials.gov, NCT01004497.

Association of the long non-coding RNA MALAT1 with the polycomb repressive complex pathway in T and NK cell lymphoma Association of the long non-coding RNA MALAT1 with the polycomb repressive complex pathway in T and NK cell lymphoma

Although the introduction of novel agents improved the survival outcomes in patients with multiple myeloma (MM), some patients died within one year (early mortality, EM) following diagnosis. In this study, we evaluated the EM rate, and investigated the risk factors associated with EM in MM patients. Retrospective data from 542 patients who were initially treated with a novel agent-containing regimen were analyzed. The median overall survival (OS) for the entire cohort was 56.5 months. The median OS in the 2010–2014 group was longer than in the 2002–2009 group (59.2 months vs. 49.1 months, P = 0.054). The rate of EM was 13.8 %, and the most common causes of EM were infection and comorbidity. In multivariate analysis, the age-adjusted Charlson comorbidity index (ACCI ≥ 4), low body mass index (BMI < 20 kg/m2), thrombocytopenia, and renal failure were significantly associated with EM. The presence of none, 1, or ≥ 2 factors was associated with a 4.1 %, 14.3 %, or 27.4 % risk of EM (P < 0.001), respectively. The median OS times were significantly different depending on the presence of factors associated with EM (P < 0.001). In conclusion, the ACCI (≥ 4), low BMI, thrombocytopenia and renal failure were strong predictors for EM in the novel agent era. The results of this study will help to identify patients at high risk for EM, and may be helpful to more accurately predict prognosis of MM patients in the novel-agent era.