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Abstract: Adult T-cell leukemia (ATL) is a fatal malignancy caused by infection with human T lymphotropic virus type-1 (HTLV-1). To search for a new biomarker of ATL, we analyzed sera from ATL patients using 1ys. The spectral comparison of ATL patients with HTLV-1 carriers and healthy volunteers showed that the intensities of five peaks (1779, 1866, 2022, 4467, and 8930m/z) were significantly increased in ATL, while those of four peaks (4067, 4151, 8130, and 8597m/z) were decreased. From these differentially expressed peaks, we chose peaks of 1779, 1866, and 2022m/z as biomarker candidates of ATL. MS/MS ion search using tandem mass spectrometry and immunoprecipitation assay using anti-C3 antibody showed that factors derived from these candidate peaks were identified as C3f, which is a component of the complement system and a fragment of complement C3. These results indicate that the complement system was activated in ATL. Further analysis of markers specific to the activation pathways (classical, alternative, and lectin pathways) in the complement system showed that the serum concentration of the marker of the lectin pathway was significantly higher in ATL patients. These results suggest that activation of the complement system in ATL occurs mainly through the lectin pathway. [Copyright &y& Elsevier]

AbstractBackground: Although thrombopoietin (TPO) is mainly produced in the liver, the regulatory mechanism of TPO gene expression in hepatocytes remains unclear. The role of TPO in thrombocytopenia associated with liver cirrhosis has not been identified. Methods: We examined the effects of various growth factors and cytokines on TPO mRNA expression in adult rat hepatocytes in primary cultures using a semiquantitative reverse transcription-polymerase chain reaction assay. Results: Among them, only hepatocyte growth factor/scatter factor (HGF/SF) enhanced TPO mRNA expression; other growth factors (epidermal growth factor and transforming growth factor-β) and cytokines (erythropoietin, granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor, interleukin (IL)-3, IL-6 and interferon-γ) did not. Next, we examined TPO mRNA expression in the livers of rats with CCl4-induced cirrhosis, the effects of HGF/SF on hepatic TPO mRNA expression and peripheral platelet and bone marrow megakaryocyte counts in the cirrhotic rats. In the cirrhotic rats, both the peripheral platelet count and TPO mRNA expression in the livers were markedly decreased compared with those of the normal rats. The administration of HGF/SF to the cirrhotic rats stimulated TPO mRNA expression in the livers and resulted in significant increases of peripheral platelets and bone marrow megakaryocytes. Conclusions: These results suggest that HGF/SF is a possible regulatory factor for TPO gene expression and that HGF/SF increases platelet production through an enhancement of TPO mRNA expression in the livers of cirrhotic rats. [ABSTRACT FROM AUTHOR]

A retrospective chart survey of the clinical features of indolent adult T-cell leukemia/lymphoma (ATL) was conducted in the Miyazaki Prefecture, Japan. This study enrolled 24 smoldering-type ATLs, 10 favorable chronic-type ATLs, and 20 unfavorable chronic-type ATLs diagnosed between 2010 and 2018. Among them, 4, 3, and 10 progressed to acute-type ATLs during their clinical course. The median survival time (MST) in smoldering-type ATL and favorable chronic-type ATL was not reached, and their 4-year overall survival (OS) was 73% and 79%, respectively. Compared with this, the prognosis of unfavorable chronic-type ATL was poor. Its MST was 3.32 years, and the 4-year OS was 46% (p = 0.0095). In addition to the three features that determine the unfavorable characteristics of chronic-type ATL, namely, increased lactate dehydrogenase, increased blood urea nitrogen, and decreased albumin, the high-risk category by the indolent ATL-Prognostic Index, which was defined by an increment of soluble interleukin-2 receptor (sIL2-R) of >6000 U/mL, could explain the poor prognosis in indolent ATL patients. The level of sIL-2R might be an indicator of the initiation of therapy for indolent ATL. [ABSTRACT FROM AUTHOR]

Objective and Method: Adult T‐cell leukemia/lymphoma (ATL) is an aggressive peripheral T‐cell lymphoma with poor prognosis. We retrospectively reviewed the medical records of 312 patients with aggressive ATL and analyzed the effect of chemotherapy dose intensity on prognosis in clinical practice. Result: As first‐line therapy, 62 patients underwent best supportive care (BSC) or single‐agent chemotherapy, and 235 underwent intensive chemotherapy. The median survival time (MST) was 0.58 years in the 312 total patients, and 0.13 years and 0.75 years in the BSC/single‐agent chemotherapy group and intensive chemotherapy group, respectively. The median average relative dose intensity (ARDI) of patients who received intensive chemotherapy was 60%. We divided patients into 3 groups according to ARDI. Those in the top tertile of ARDI (ARDI ≥ 75%, n = 82) had better overall survival compared with those in the intermediate tertile (45% ≤ ARDI < 75%, n = 79) (P <.0001), with MSTs of 4.69 and 0.75 years, respectively. The occurrence of organ dysfunction and infectious complications was comparable between the two ARDI groups. Conclusion: Higher ARDI improves prognosis in patients with aggressive ATL in clinical practice. [ABSTRACT FROM AUTHOR]

Objective The efficacy of mogamulizumab in adult T-cell leukemia/lymphoma ( ATLL) was reported in a previous phase 2 study. Compared with patients in clinical trials, however, most patients in real-life settings have demonstrated worse outcomes. Method We retrospectively analyzed 96 patients with relapsed/refractory ATLL who received mogamulizumab treatment. Results Relapsed/refractory ATLL patients with a median age of 70 years received a median of five courses of mogamulizumab. Hematologic toxicity and skin rash were the most common adverse events, and both were manageable. Of 96 patients, 87 were evaluable for efficacy. The overall response rate was 36%, and the median progression-free survival ( PFS) and overall survival ( OS) from the start of mogamulizumab therapy were 1.8 and 4.0 months, respectively. Of the original 96 patients, only 25 fulfilled the inclusion criteria of the phase 2 study. Those who met the criteria demonstrated longer median PFS and OS durations of 2.7 and 8.5 months, respectively. The median OS from diagnosis in relapsed/refractory ATLL patients receiving mogamulizumab was 12 months, longer than the 5.8 months in a historical cohort without mogamulizumab. Conclusion In clinical practice, mogamulizumab exhibited antitumor activity in patients with relapsed/refractory ATLL, with an acceptable toxicity profile. Mogamulizumab therapy improved the OS of ATLL patients. [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]

Although malignancy is a fatal complication of end-stage renal disease (ESRD) requiring haemodialysis, successful treatment of haematological malignancies has been rarely reported. We describe the case of a 64-year-old man who presented with non-Hodgkin’s lymphoma (NHL; clinical stage, IVB) concomitant with ESRD. Before chemotherapy, haemodialysis was initiated, and one course of dose-adjusted CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy followed by eight courses of rituximab therapy were administered according to the performance status and degree of organ dysfunction. Consequently, the patient was disease free for 27 months. Thus, rituximab plus CHOP combination therapy was effective for NHL concomitant with ESRD. [ABSTRACT FROM PUBLISHER]

We previously reported that monotherapy with carbapenem or cefepime exhibited efficacy equivalent to cefepime plus an aminoglycoside as initial therapy for febrile neutropenia (FN), achieving an adequate response in two-thirds of the patients. However, only one-third of the remaining poor responders to monotherapy became afebrile after an aminoglycoside was added to the initial carbapenem or cefepime. The present study was designed to evaluate the benefit of intravenous ciprofloxacin for neutropenic patients with fever who were refractory to initial therapy given for the first 3 days. Patients with FN—as defined by an axillary temperature ≥37.5°C and a neutrophil count [ABSTRACT FROM AUTHOR]

For the oncogenesis of many malignancies, it is crucial to prevent the shortening of the telomeres by the action of telomerase. In this study, clinical data and disease outcomes were analyzed in conjunction with the telomerase activity (TA) and telomere length (TL) of peripheral blood mononuclear cells. The study was carried out in 22 patients with adult T-cell leukemia (ATL) (7 chronic and 15 acute types) and in 13 asymptomatic human T-lymphotropic virus type 1 (HTLV-1) carriers. The mean values of TA in acute and chronic type patients were 13.8 and 1.6 total product generated (TPG) units, respectively, as determined by telomeric repeat amplification assays. The mean TA values in HTLV-1 carriers and healthy volunteers were 1.8 and 0.7 TPG, respectively. The mean TA value in acute type patients was significantly higher than in the three other subject groups. The mean TL values in patients with acute and chronic types were 5.39 and 4.38 Kb, respectively, while the mean TL values in HTLV-1 carriers and healthy volunteers were 7.69 and 7.06 Kb, respectively. The mean TL values in all ATL patients and in non-ATL subjects were 5.2 and 7.3 Kb, respectively. The former value is significantly shorter than the latter ( p  < 0.01). Neither TA nor TL of ATL cells showed any significant association with the number of ATL cells, serum soluble interleukin-2 receptor, or serum lactate dehydrogenase in the peripheral blood of acute type patients. This suggests that the levels of TA and TL did not reflect the ATL tumor load. The median survival period of acute ATL patients with high TA and shortened TL was 0.47 years, however, which was significantly shorter than that of acute ATL patients with low TA and normal TL (4.21 years) ( p  < 0.002). These data suggest that high TA and shortened TL were associated with poorer prognosis, and that TA and TL may be novel markers for the prognosis of ATL patients. [ABSTRACT FROM AUTHOR]

A 49-year-old man, who had a 3-year history of liver dysfunction but had not been treated, was admitted to the hospital with a sudden onset of fever and generalized muscle pain. He subsequently developed generalized purpura with scattered hemorrhagic bullae of the skin and massive bloody stools. Aeromonas sobria was proven by culture of both blood and bullous fluid. In spite of the extensive treatment with antibiotics and other medications in the intensive care unit (ICU), the patient went into septic shock and died 2 days after admission. Pathological examination on autopsy revealed segmental necrotizing gastroenteritis with bacterial colonies and alcoholic liver cirrhosis, in addition to extensive severe soft tissue damage involving cellulitis and rhabdomyolysis and epidermolysis. Although the prognosis for Vibrio vulnificus infection with severe soft tissue damage in patients with liver cirrhosis, malignancy, diabetes mellitus or other pre-existing diseases is poor, the unfavorable progression of Aeromonas species, especially A. sobria infection is rare. This is thought to be the first report of an autopsied case. [ABSTRACT FROM AUTHOR]

The prognosis of multiple myeloma (MM) has improved with the introduction of novel agents. These data are largely derived from clinical trials and might not reflect real-world patient outcomes accurately. We surveyed real-world data from 284 patients newly diagnosed with MM between 2010 and 2018 in Miyazaki Prefecture. The median follow-up period was 32.8 months. The median age at diagnosis was 71 years, with 68% of patients aged >65 years. The International Staging System (ISS) stage at diagnosis was I in 18.4% of patients, II in 34.1%, and III in 47.5%. Bortezomib-containing regimens were preferred as initial treatment; they were used in 147 patients (51.8%). In total, 80% of patients were treated with one or more novel agents (thalidomide, lenalidomide, or bortezomib). Among 228 patients who were treated with novel agents as an initial treatment, the overall response rate (partial response (PR) or better) to initial treatment was 78.4%, and the median time to next treatment (TTNT) was 11.6 months. In the multivariate analysis, PR or better responses to initial treatment were independently favorable prognostic factors for TTNT. The median survival time after initial therapy for patients with novel agents was 56.4 months and 3-year overall survival (OS) was 70.4%. In multivariate analysis, ISS stage I/II disease and PR or better response to initial treatment, and autologous stem cell transplantation (ASCT) were identified as independent prognostic factors for overall survival (OS). [ABSTRACT FROM AUTHOR]

Presents a letter to the editor, on causes of acute hepatic failure.

An abstract of the article "Downregulation of CDKN1A in Adult T-Cell Leukemia/Lymphoma despite Overexpression of CDKN1A in Human T-Lymphotropic Virus 1-Infected Cell Lines," by Masaaki Watanabe, Shingo Nakahata, Makoto Hamasaki, Yusuke Saito, Yohei Kawano, Tomonori Hidaka, Kiyoshi Yamashita, Kazumi Umeki, Tomohiko Taki, Masafumi Taniwaki, Akihiko Okayama and Kazuhiro Morishita is presented.