BackgroundAntioxidants have been shown to enhance the proliferation of adipose-derived mesenchymal stem cells (ADMSCs) in vitro, although the detailed mechanism(s) and potential side effects are not fully understood.In this study, human ADMSCs cultured in ImF-A medium supplemented with antioxidants (N-acetyl-l-cysteine and ascorbic acid-2-phosphate) and fibroblast growth factor 2 (FGF-2) were compared with ADMSCs cultured with FGF-2 alone (ImF) or with FGF-2 under 5% pO2 conditions (ImF-H).ResultsDuring log-phase growth, exposure to ImF-A resulted in a higher percentage of ADMSCs in the S phase of the cell cycle and a smaller percentage in G0/G1 phase. This resulted in a significantly reduced cell-doubling time and increased number of cells in the antioxidant-supplemented cultures compared with those supplemented with FGF-2 alone, an approximately 225% higher cell density after 7 days. Western blotting showed that the levels of the CDK inhibitors p21 and p27 decreased after ImF-A treatment, whereas CDK2, CDK4, and CDC2 levels clearly increased. In addition, ImF-A resulted in significant reduction in the expression of CD29, CD90, and CD105, whereas relative telomere length, osteogenesis, adipogenesis, and chondrogenesis were enhanced. The results were similar for ADMSCs treated with antioxidants and those under hypoxic conditions.ConclusionAntioxidant treatment promotes entry of ADMSCs into the S phase by suppressing cyclin-dependent kinase inhibitors and results in rapid cell proliferation similar to that observed under hypoxic conditions.

1875 Introduction: The aim of this study is to validate the clinical utility of a flow cytometric scoring system (FCSS) (1)in the diagnosis and prognosis of MDS by quantifying myeloid and monocytic dyspoiesis and correlating the accumulation of abnormalities to clinical outcome. Methods: The BM samples were characterized by the FCSS from 56 consecutive, newly diagnosed MDS patients who were morphologically classified as RA (n=3), MDS-U (n=1), RCMD/RCMD-RS (n=32), RAEB-1 (n=12) and RAEB-2 (n=8) from January 2005 to December 2009. Three-color FCM was performed on total nonerythroid BM cells with a standardized panel of monoclonal antibodies (Table 1). The final FCSS was based on the independent analysis of data by 2 investigators (S.C.C., T.F.W.,) who were blinded to MDS/non-MDS category and clinical outcomes. The FCSS were categorized as normal/mild (0 or 1 point), moderate (2 or 3 points), or severe (4 or more points). The results of FCSS were compared with findings in 27 non-MDS cytopenic patients as the control, including diagnosis of aplastic anemia (n=7), iron deficiency anemia (n=3), folic acid or vitamin B12 deficiency anemia (n=6) and idiopathic thrombocytopenia purpura (n=11). FCSS scores were retrospectively compared with marrow blast counts, cytogenetics, hematologic parameters, IPSS and WHO categorization to assess the utility in diagnosis and prognosis of MDS. Follow-up of patients continued until May 2010, with mortality observed in 30 (54%) patients. The patient characteristics are summarized in Table 2. Nearly all MDS patients underwent supportive care rather than hypomethylation agents(n=3), chemotherapy(n=4) or haematopoietic stem cell transplantation(n=0). Results: The FCSS scores were significantly higher in patients with MDS than those in the non-MDS control (3 vs. 0, P < .0001). A flow score of 2 or more allowed for a specificity of 100% with 75% sensitivity in diagnosing MDS. The FCSS scores correlated directly with IPSS scores (n=40, R=.5327, P =.0004) and WHO classification (n= 56, R=.5163, P<.0001) but did not correlated with IPSS cytogenetic risk categories (n=40, P= .7738). The median survival were 6 months, 19 months and not reach for MDS patients with severe, moderate and mild FCSS scores, respectively (n=56, P = .0018)(Figure 1). The Multivariate analyses using Cox proportional hazard model in a stepwise manner demonstrated the FCSS risk categories was an independent prognostic factor (P=.0020) after adjusting for sex, age (above 70 year-old or not) and IPSS risk categories. Furthermore, among 32 patients classified as RCMD/RCMD-RS, the median survival were 2 months, 13 months and not reach for patients with severe, moderate and mild FCSS scores, respectively (n=32, P = .0045) (Figure 2). Conclusion: These results demonstrate that quantifying aberrancies in myelomonocytic lineage by FCSS is very useful in MDS diagnosis. As shown in a bone marrow transplant study the FCSS also predicts outcome in conventionally treated patients and may give a more accurate prognosis especially among patients classified as RCMD subgroup. Reference: (1) Wells, DA et Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation Blood 102: 394–403, 2003. Disclosures: No relevant conflicts of interest to declare.

Primary effusion lymphoma (PEL) is an unusual form of non-Hodgkin's lymphoma, which is characterized by lymphomatous effusion in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV). We describe a 54-year-old man with HIV-negative PEL, with a history of hepatitis B virus-related liver cirrhosis. Both abdominal and pleural cavities were involved; no solid tumor masses were found and bone marrow investigations were normal. The ascites and pleural effusion contained numerous pleomorphic lymphoid cells. Immunophenotyping was positive for CD138. Chromosome study showed complex cytogenetics. The genomic human herpesvirus-8 was detected in the lymphoma cells. It is postulated that the immunosuppressed state in this patient may have been caused by cirrhosis. The patient received four cycles of chemotherapy of CHOP and Picibanil (OK-432) intraperitoneal administration. However, no durable remission was achieved. Adefovir failed to halt the progressive liver failure after the development of YMDD mutant related to lamivudine. He died of sepsis and hepatic failure.

Although anthracyclines are recognized as efficacious chemotherapeutic agents with broad-spectrum anticancer activity, their clinical use is limited by their chronic accumulative dose-dependent cardiac toxicity. Three forms of anthracycline-induced cardiotoxicity have been described: acute or subacute cardiac injury, chronic cardiotoxicity resulting in cardiomyopathy, and late-onset ventricular dysfunction with arrhythmias. Acute and subacute anthracycline toxicities are most often manifested as arrhythmias, pericarditis-myocarditis, subclinical cardiomyopathy, left ventricular dysfunction, and sudden death [1,2]. However, acute cardiac toxicity is uncommon and is usually subclinical in nature or is associated with mild clinical symptoms lacking significant consequences. This report describes a case of severe subacute congestive heart failure (CHF) and ventricular tachycardia (VT) developing in response to the first exposure to idarubicin.A pale-faced 34-year-old woman presented to our haematology outpatient clinic with the complaint of general malaise of 1 month's duration. No systemic disease had occurred prior to this illness and she had no history of coronary artery disease, smoking, or illegal substance abuse. Bone marrow examination confirmed the presence of acute myeloid leukaemia (AML), M6 subtype. Induction chemotherapy with idarubicin and cytarabine was therefore initiated. Idarubicin was administered at 12 mg m -2 day -1 for 3 days by a 30-min intravenous infusion, and cytarabine was administered at 100 mg m -2 day -1 for 7 days by continuous (24 h) intravenous infusion. A neutropenic fever developed on day 10,and empirical antibiotic therapy with piperacillin/tazobactam and amikacin was prescribed. Because the fever persisted, antibiotic therapy was changed to meropenem on day 15 and fluconazole was added on day 18. When blood laboratory analyses conducted on day 17 revealed the presence of hypokalaemia, potassium (KCl solution) was given intravenously.Even after aggressive potassium chloride supply, serum levels of potassium on day 27 were 2.53 mmol l -1 . On day 20, the patient displayed tachypnoea and shortness of breath. Chest x-ray revealed cardiomegaly and right pleural effusion. Echocardiography performed on day 26 revealed chamber dilation of the left atrium and left ventricle, generalized hypokinetic wall motion, and a left ventricular ejection fraction (LVEF) of 23% (Figure 1).Prior to the development of CHF,the patient exhibited no symptoms or signs of arrhythmia or pericarditis-myocarditis. Cardiac marker measurements of creatine kinase isoenzyme (CK-MB) and troponin-I on day 24 were all within normal ranges.Frequent ectopic premature ventricular beats were detected on day 27, with the arrhythmia progressing to VT and ventricular fibrillation on day 28. Because of a sudden loss of consciousness, cardiopulmonary resuscitation with defibrillation was performed immediately. Intubation with ventilatory support and an intra-arterial balloon pump were placed to manage cardiogenic shock and pulm...

An increased frequency of the Hp 2-2 genotype was associated with NPC. The Hp 2 allele was also overexpressed in NPC patients. NPC patients with the Hp 2-2 genotype had advanced T stage and a larger primary tumor volume. Hp 2-2 may be a negative prognostic factor in NPC.