KL-6, a mucinous high-molecular weight glycoprotein expressed on type 2 pneumocytes, has been shown to be elevated in the serum and bronchoalveolar lavage fluid of patients with interstitial ...pneumonitis (IP). We measured the serum levels of KL-6 in patients after they had undergone allogeneic bone marrow transplantation (BMT) to determine whether KL-6 could be a clinically useful indicator for the development of IP. The serum concentrations of KL-6 were determined by a sandwich-type enzyme-linked immunosorbent assay using an anti-KL-6 monoclonal antibody. A total of 1028 samples were tested from 76 patients (78 transplantations) who received BMTs. The KL-6 values were markedly elevated in patients with pulmonary complications, but not in those with acute and chronic graft-versus-host disease, hemorrhagic cystitis, herpes encephalitis, sepsis, and veno-occlusive disease. The serum levels of KL-6 from patients with pulmonary complications were significantly higher than from those without pulmonary complications (P < .001) and those with other complications (P < .001). Of the 12 patients with pulmonary complications, 6 had idiopathic IP (IIP). The levels were not high at the onset of IIP. Four of 6 IIP patients showed marked elevations of KL-6 levels in parallel with the severity of IP and died of respiratory failure without response to treatment. Assessment of serum KL-6 levels might not be useful for the early diagnosis of IP, but may be a useful indicator for monitoring the severity of IP after BMT.
Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from ...the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in HD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect.
In situ
hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10
+ cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.
We previously reported that all-trans retinoic acid (ATRA) inhibited growth in HTLV-I- positive T-cell lines and fresh cells from patients with adult T-cell leukemia. We here confirmed the clinical ...effects of ATRA in 20 patients with ATL. Twenty patients (n=20) with median age of 56 years (range 35–68 years) diagnosed with ATL received ATRA orally. ATRA was administered for a median of 25.7 days (range 14–56 days). Efficacy was described below; no CR case, PR case was 55%, NR case was 45%. In 7 acute cases, PR case was 4 (20%) and NR case was 3 (15%). In 3 lymphoma cases, no NR case and 3 PR cases (15%) was found. In 4 chronic cases, PR case was 1 (4%) and NR case was 3 (15%). In 6 skin type. PR case was 3 (15 %) and NR case was 3 (15%). Major side effects were headache (n=5), transient liver dysfunction (n=2), hyperlipidemia (n=2) and anorexia (n=1). No major toxicity was observed. These results indicated that ATRA might be a useful agent for skin involvement of ATL with safety.
It has been known that non-Hodgkin's lymphomas (NHL) are a major complication in human immunodeficiency virus (HIV) infection, and a major cause of death in HIV infected patients. Recently, it has ...been reported that highly active anti-retroviral therapy (HAART) declines the incidence of HIV-related lymphoma. In this study, we tried to make in vitro model of HIV-related lymphoma by Epstein-Barr virus transformation, and to examine the cellular and molecular characteristics of the HIV-related lymphoma cells derived from patients with HIV infection. PBMCs from 10 patients HIV infection and 10 HIV-negative normal individuals were obtained by Ficoll-Paque (Amersham Biosciences Corp. NJ) density gradient centrifugation. Lymphoblastoid cell lines (LCL) were obtained from each patient through transformation with Epstein-Barr virus (B95-8). Cells were cultured with RPMI 1640 medium (GIBCO, Grand Island, NY) supplemented with 10% fetal calf serum (FCS) (JRH Bioscences, Inc. Lenexa, Kansas), antibiotics, and L-glutamine and maintained at 37°C in an atmosphere containing 5% CO2. FACS analysis revealed the cells to be CD3−, CD4−, CD8−, CD5−, CD19+, CD20+, HLA-class I+, -class II+. After the establishment of LCLs, to obtain a highly purified population, CD19+LCLs were sorted on a FACS Vantage SE (Becton Dickinson, San Jose, CA). The purity of each CD19+LCLs population evaluated by FACS analysis was always higher than 98%. After growth advantage of LCLs, growth ability of the LCLs from HIV patients was examined by MTT assay. In results, there is no significant difference of growth ability between LCLs derived from HIV patients and those derived from normal individuals. Furthermore, the expression of cell adhesion molecules (CD11a, CD11b, CD18, CD50, and CD54) of LCLs was observed by FACS. The results showed that the expression of CD18 on LCLs derived from HIV patients was enhanced significantly in compared to those of normal LCLs. This phenomenon seems to be consistent with development of primary central nervous system (CNS) lymphoma. Furthermore, effects of anti-retroviral drugs to the expression of the adhesion molecules are examined. Somatic hypermutation of immunoglobulin heavy chain variable gene (IGHV) has been detected over 90% of HIV-related lymphoma. The effects of HAART to hypermuation of IGHV of LCL derived from HIV patients will be addressed.
This prospective multicenter study was performed to clarify the efficacy and safety of micafungin (MCFG) as an empirical antifungal therapy for suspected fungal infection in patients with ...hematological disorders and neutropenia. Three hundred and eighty-eight patients were enrolled; 151 patients with possible fungal infection diagnosed by radiological imaging or serological testing and 237 patients with refractory fever were included in this study. The mean dose and duration of treatment with MCFG were 154.6 mg/day and 14.0 days, respectively. The clinical response rate for patients with possible fungal infection and refractory fever was 60.1% and 65.3%, respectively. Even in persistent neutropenic patients with a neutrophil count of <500/μL throughout the MCFG treatment, the clinical response rate was 46.9%. Ninety-one drug-related adverse events (DAEs) were observed in 56 patients (14.4%) and 9 serious DAEs were observed in 6 patients (1.5%). Neither daily dose nor duration of MCFG treatment affected the incidence of DAEs. It was confirmed that MCFG has adequate clinical efficacy and is safe for the treatment of suspected fungal infections in patients with hematological disorders and neutropenia.
Abstract
A study to evaluate WT1 mRNA expression levels in peripheral blood (PB) and bone marrow aspirate (BM) was conducted in 172 patients, including 115 with myelodysplastic syndromes (MDS), in ...Japan. The level of WT1 mRNA expression was evaluated according to the French-American-British (FAB) and World Health Organization (WHO) classifications (2001, 2008) and using the International Prognostic Scoring System and the WHO Prognostic Scoring System scales. WT1 mRNA expression levels in PB and BM were well correlated (r = 0.85), and they tended to increase with disease stage progression and in those at higher risk of leukemic transformation. WT1 mRNA expression can be a useful marker for the diagnosis and risk evaluation of MDS.
Abstract 1037▪▪This icon denotes a clinically relevant abstract
In the IDSA guideline published in 2010 on the use of antimicrobial agents in neutropenic cancer patients, monotherapy with an ...anti-pseudomonal beta-lactam agent, such as cefepime (CFPM), carbapenem meropenem (MEPM) or imipenem-cilastatin (IPM), or piperacillin-tazobactam, is recommended as an empiric therapy for high risk febrile neutropenia (FN) patients. There have been few reports on the efficacy of cefozopran (CZOP), one of the 4thgeneration beta-lactams, in the treatment of such patients. We conducted an open-label randomized controlled study to evaluate the clinical efficacy of CZOP, MEPM, or IPM in high-risk FN adult patients with hematologic malignancies and solid tumors, using CFPM as a control.
In this trial, 386 patients registered from 23 centers were randomized to receive either 4thgeneration beta-lactam (CFPM 2g, q12h IV or CZOP 2g, q12h IV) or carbapenem (MEPM 1g, q12h IV or IPM 1g, q12h IV). The primary endpoint was response to treatment defined as complete defervescence by day 7 with improvement in infection-related symptoms and laboratory findings. The clinical data were analyzed both by intention to treat and per protocol. We also evaluated the efficacy of each of the initial four drugs at days 3 to 5as a secondary endpoint.
386 patients received the assigned antibiotic (CFPM: n=95, CZOP: n=98, MEPM: n=96, IPM: n=97) and 377 were evaluated for efficacy (CFPM: n=94, CZOP: n=95, MEPM: n=94, IPM: n=94). The 4 groups were comparable in terms of the baseline characteristics, including as age (median: 59 years (range: 17–87)), sex (male: n=215, female: n=171), body weight (median: 55 kg (range: 32–100)), underlying malignancy (leukemia: n=212 (54.9%), lymphoma: n=122 (31.6%), multiple myeloma: n=37 (9.6%), myelodysplastic syndrome: n=6 (1.6%), and other malignancy: n=9 (2.3%)), duration of initial antibiotic therapy (median: 7 days (range: 1–29)), median duration of severe neutropenia (neutrophil count < 100×106/L) (median: 6 days (range: 0–56)) and MASCC score (median: 21 (range:3–26)). Only neutrophil count at onset of IPM was significantly lower compared to the other treatments (CFPM: 38×106/L, CZOP: 35 x106/L, MEPM: 18×106/L, and IPM: 3×106/L, p=0.003). In intention-to-treat analysis, the response rates at day 7 were not significantly different among the four arms (CFPM: 63%, CZOP: 59%, MEPM: 61%, IPM: 69% (P=0.52)). The three antibiotics investigated in this trial were as effective as the reference agent, CFPM, in both the intention-to-treat and per-protocol populations. In both the intention-to-treat and per protocol analyses, success rates of the initial therapy at days 3 to 5 were not significantly different among four drugs CFPM: 52 and 54%, CZOP: 46 and 47%, MEPM: 54 and 55%, IPM: 49 and 53% (P=0.70 and 0.68, respectively).
CZOP, MEPM, and IPM were as effective as CFPM for adult FN patients with hematological malignancies and solid tumors as an empiric therapy.
Tamura:Kyowa Hakko Kirin Co., Ltd,: Consultancy.
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