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A new entity, namely early/prefibrotic primary myelofibrosis (PMF), was introduced as a subtype of PMF in the 2016 revised World Health Organization (WHO) criteria for myeloproliferative neoplasms (MPN). It was diagnosed based on histopathological features of bone marrow (BM) biopsy specimens together with clinical parameters [leukocytosis, anemia, elevated lactate dehydrogenase (LDH) values, and splenomegaly]. The aim of this study was to evaluate the prevalence of early/prefibrotic PMF in patients who were previously diagnosed with ET, and to compare clinical features at diagnosis and outcomes between early/prefibrotic PMF and essential thrombocythemia (ET) patients. BM biopsy samples obtained at the time of ET diagnosis were available in 42 patients. Sample reevaluation according to the 2016 revised WHO criteria revealed that early/prefibrotic PMF accounted for 14% of patients who were previously diagnosed with ET, which was comparable to the rates in previous reports. Compared to patients with ET, patients with early/prefibrotic PMF had higher LDH values and higher frequencies of splenomegaly. Overall, myelofibrosis-free and acute myeloid leukemia-free survivals were comparable between the 2 groups. Accurate diagnosis is required to clarify the clinical features of Japanese ET patients. [ABSTRACT FROM AUTHOR]

Polycythemia vera (PV) and essential thrombocythemia (ET) are associated with life-threatening thrombohemorrhagic events, and disease progression and development of non-hematological malignancies also reduce long-term survival. We retrospectively surveyed thrombohemorrhagic events and overall survival (OS) in 62 PV and 117 ET patients. The cumulative incidences of thrombohemorrhagic events in PV and ET patients were 11.3 and 10.3%, and the incidence rates were 2.42 and 1.85 per 100 person-years. The combined incidence rates of disease progression and development of non-hematological malignancies in PV and ET patients were 1.73 and 1.69 per 100 person-years. The incidence rates of thrombohemorrhagic events in our Japanese PV/ET patients were lower than those reported by most Western studies, but were comparable to those in the largest prospective observational study in ET patients. The combined incidence rates of disease progression and development of non-hematological malignancies were similar between Japanese and Western PV/ET patients. In ET patients, the conventional risk stratification model based on the presence of advanced age or history of thrombosis was useful to predict thrombosis risk, and both the conventional model and the International Prognostic Score of thrombosis in ET based on the above 2 risk factors plus increased leukocyte count could predict poor survival. [ABSTRACT FROM AUTHOR]

Fibronectin (FN) plays important roles in the proliferation, differentiation, and maintenance of megakaryocytic-lineage cells through FN receptors. However, substantial role of FN receptors and their functional assignment in proplatelet-like formation (PPF) of megakaryocytes are not yet fully understood. Herein, we investigated the effects of FN receptors on PPF using the CHRF-288 human megakaryoblastic cell line, which expresses VLA-4 and VLA-5 as FN receptors. FN and phorbol 12-myristate 13-acetate (PMA) were essential for inducing PPF in CHRF-288 cells. Blocking experiments using anti-β1-integrin monoclonal antibodies indicated that the adhesive interaction with FN via VLA-4 and VLA-5 were required for PPF. PPF induced by FN plus PMA was accelerated when CHRF-288 cells were enforced adhering to FN by TNIIIA2, a peptide derived from tenascin-C, which we recently found to induce β1-integrin activation. Adhesion to FN enhanced PMA-stimulated activation of extracellular signal-regulated protein kinase 1 (ERK1)/2 and enforced adhesion to FN via VLA-4 and VLA-5 by TNIIIA2-accelerated activation of ERK1/2 with FN plus PMA. However, c-Jun amino-terminal kinase 1 (JNK1), p38, and phosphoinositide-3 kinase (PI3K)/Akt were not stimulated by FN plus PMA, even with TNIIIA2. Thus, the enhanced activation of ERK1/2 by FN, PMA plus TNIIIA2 was responsible for acceleration of PPF with FN plus PMA. [ABSTRACT FROM AUTHOR]

We performed a retrospective population-based cohort study of acute myeloid leukemia (AML) in Miyazaki Prefecture, Japan. Over 6 years, we diagnosed 221 patients (211 adults and 10 children) with AML, indicating an incidence of AML in Miyazaki Prefecture of 3.2 per 100,000 per year. In 193 adult patients with non-acute promyelocytic leukemia (APL), the proportion of patients with myelodysplasia, unfavorable risk karyotypes, antecedent hematologic diseases, prior chemotherapy for other malignancies, and small proportion of blasts in the marrow was higher in patients ≥65 years, and patients with poor performance status (PS) and higher WBC counts at diagnosis were more prevalent among patients ≥75 years. One-third of the adult non-APL patients met the inclusion criteria usually applied in clinical trials: de novo AML, age ≤64 years with PS 0-2 and no key organ dysfunction. The 5-year overall survival (OS) rate of adult non-APL patients was 21.1 % (patients ≤64 years, 33.8 %; 65-74 years, 21.6 %; ≥75 years, 0 %). Multivariate analysis revealed that French-American-British subtypes M0, M6, and M7, poor PS (3, 4), unfavorable risk karyotypes, and higher WBC counts at diagnosis were independent adverse prognostic factors associated with OS. This analysis provides real world data. [ABSTRACT FROM AUTHOR]

Background: Secondary central nervous system lymphoma (SCNSL) without extra-central nervous system (CNS) involvement is characterized by isolated secondary CNS relapse in malignant lymphoma patients. SCNSL is a rare disease, and no standard treatment has yet been established. Patients and methods: To elucidate the clinical characteristics and outcomes of SCNSL, we retrospectively analyzed 12 patients (median age 67 years) in Miyazaki prefecture for the last 5 years. Results: The initial histological diagnoses of the patients were diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma, and adult T-cell lymphoma in 9, 2, and 1 patient, respectively. We focused on analysis of the 9 SCNSL cases originating from DLBCL. The locations of CNS relapse were the cerebral hemisphere, basal ganglia, and cerebellum in 7, 1, and 1 patient, respectively. Three patients were treated with high-dose methotrexate (HD-MTX) therapy; 4 with whole-brain radiation therapy (WBRTX); and 1 with both HD-MTX and WBRTX. The remaining patients were treated with rituximab. Partial remission was achieved in 6 out of 9 patients (67%); the other 3 patients (33%) did not respond to therapy. Median survival of the 9 patients with CNS relapse was 253 days; 6 of the 9 patients survived for more than 6 months. As of March 2011, 2 HD-MTX group patients but none of the WBRTX group patients were alive. Conclusions: In this retrospective study, 6 of 9 patients with SCNSL originating from DLBCL survived for more than 6 months. Both HD-MTX and WBRTX had clinical benefits in the treatment of SCNSL. [ABSTRACT FROM AUTHOR]