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Abstract Deferasirox is an oral iron‐chelating agent having possible antileukemia and immune modulatory effects. Few reports have evaluated deferasirox in the setting of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We investigated the impact of deferasirox after allo‐HSCT in acute myeloid leukemia (AML). Of 326 consecutive patients undergoing allo‐HSCT in remission, analysis of 198 patients not receiving deferasirox revealed the negative prognostic effect of hyperferritinemia (≥1000 ng/mL) before and after allo‐HSCT on survival mainly due to increase in relapse. Of 276 patients with hyperferritinemia at 1 month after allo‐HSCT, 128 patients (46%) received deferasirox. Deferasirox induced a faster decline in serum ferritin level with a manageable safety profile, which significantly reduced relapse rather than nonrelapse mortality, resulting in better survival compared to patients not receiving deferasirox. Of note, the deferasirox group had a significantly higher incidence of chronic graft‐vs‐host disease, indicating improved graft‐vs‐leukemia (GVL) effects evidenced by the presence of suppressed regulatory T cells and sustained higher proportion of NK cells in peripheral blood. This study firstly demonstrates the improved survival and restoration of GVL effects of patients with AML by deferasirox, which also clarifies the detrimental effect of hyperferritinemia through after allo‐HSCT.

Although vascular endothelial growth factor-C (VEGF-C) is known to be expressed in acute myeloid leukemia (AML) blasts, the relevance of VEGF-C in the clinical setting remains to be fully explored. We examined the effect of VEGF-C on achievement of complete remission (CR) in adult de novo AML and immune cell population profiles according to VEGF-C mRNA expression. In comparison of VEGF-C expression between the no-CR and CR groups, the CR group showed a trend toward higher levels of plasma VEGF-C (P = .088), whereas mRNA expression of VEGF-C was downregulated (P = .008). Next, patients with continuous data for VEGF-C were divided into two groups (low vs. high) by a ROC curve analysis. The low- versus high-level groups for plasma VEGF-C (RR of 0.20, P = .030), mRNA expression of VEGF-C (RR of 18.75, P = .003), and the ratio of plasma level to mRNA expression (RR of 0.05, P = .007) were potential predictors of CR on univariate analysis. After adjusting for potential clinical factors including genetic group, multivariate analyses revealed that high VEGF-C mRNA expression was an independent risk factor for failure of induction chemotherapy. Furthermore, patients with high VEGF-C mRNA expression had a lower frequency of NKT and CD8+ cells and showed a trend for a lower frequency of NK cells. These results suggest that interruption of VEGF-C signaling might be a potential therapeutic target for antileukemic treatment in AML patients.

Abstract Wilms’ tumor gene 1 (WT1) expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL) and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen) for WT1 monitoring. High WT1 expression (>120 copies/104 ABL1) after consolidation and at early period (3 months) after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40) showed a significantly higher relapse rate (30.5 vs. 6.9%, P

BACKGROUND:The risk of developing tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is expected to be relatively high in an intermediate TB burden country. This single-center retrospective study was conducted to investigate risk factors and the incidence of TB after allogeneic HSCT. METHODS:From January 2004 to March 2011, 845 adult patients were enrolled. Starting April 2009, patients were given isoniazid (INH) prophylaxis based on interferon-γ release assay results. The incidence of TB was analyzed before and after April 2009, and compared it with that of the general population in Korea. RESULTS:TB was diagnosed in 21 (2.49%) of the 845 allogeneic HSCT patients. The median time to the development of TB was 386 days after transplantation (range, 49-886). Compared with the general population, the standardized incidence ratio of TB was 9.10 (95% CI; 5.59-14.79). Extensive chronic graft-versus-host disease (GVHD) was associated with the development of TB (P = 0.003). Acute GVHD, conditioning regimen with total body irradiation and conditioning intensity were not significantly related. INH prophylaxis did not reduce the incidence of TB (P = 0.548). Among 21 TB patients, one patient had INH prophylaxis. CONCLUSION:Allogeneic HSCT recipients especially those who suffer from extensive chronic GVHD are at a high risk of developing TB. INH prophylaxis did not statistically change the incidence of TB, however, further well-designed prospective studies are needed.

Background Since it was suggested that B cells play a role in the pathogenesis of chronic graft-versus-host disease, rituximab, an anti-CD20 monoclonal antibody targeting B cells, has been shown to be effective in steroid-refractory, chronic graft-versus-host disease. However, most of the data were from small numbers of patients or retrospective analyses. We, therefore, conducted a multicenter phase II study to confirm the efficacy of this treatment strategy that targets B cells.Design and Methods We diagnosed and evaluated chronic graft-versus-host disease according to the National Institute of Health criteria for clinical trials on this condition. The treatment consisted of weekly intravenous infusions of rituximab for 4 weeks followed by monthly rituximab for 4 months. We evaluated the patients’ responses and monitored their disease activity until their final visit, which was on day 365. We also assessed the patients’ subsequent quality of life and serum levels of B-cell-activating factor of the tumor necrosis factor family.Results Among 37 patients enrolled (median age, 29 years; range 8–57 years), 32 patients responded to rituximab with 8 complete and 24 partial responses. Twenty-one patients maintained their response for 1 year, so their steroid treatment was discontinued or its dose reduced (21/37, or 56.8%), and their scores representing quality of life were improved although these changes were not statistically significant. The responses were better for clinical manifestations of the skin, oral cavity and musculoskeletal system (response rate, 71.4–100%) than for other organs. However, infectious complications and primary disease relapse accounted for the majority of treatment failure. The pre-treatment serum level of B cell-activating factor of the tumor necrosis factor family was not associated with better treatment outcome (P=0.147).Conclusions Rituximab could improve clinical responses and quality of life of patients with steroid-refractory chronic graft-versus-host disease, although such patients may need active prophylaxis against infection.

Multi-exposure image fusion inevitably causes ghost artifacts owing to inaccurate image registration. In this study, we propose a deep learning technique for the seamless fusion of multi-exposed low dynamic range (LDR) images using a focus-pixel sensor. For auto-focusing in mobile cameras, a focus-pixel sensor originally provides left (L) and right (R) luminance images simultaneously with a full-resolution RGB image. These L/R images are less saturated than the RGB images because they are summed up to be a normal pixel value in the RGB image of the focus pixel sensor. These two features of the focus pixel image, namely, relatively short exposure and perfect alignment are utilized in this study to provide fusion cues for high dynamic range (HDR) imaging. To minimize fusion artifacts, luminance and chrominance fusions are performed separately in two sub-nets. In a luminance recovery network, two heterogeneous images, the focus pixel image and the corresponding overexposed LDR image, are first fused by joint learning to produce an HDR luminance image. Subsequently, a chrominance network fuses the color components of the misaligned underexposed LDR input to obtain a 3-channel HDR image. Existing deep-neural-network-based HDR fusion methods fuse misaligned multi-exposed inputs directly. They suffer from visual artifacts that are observed mostly in saturated regions because pixel values are clipped out. Meanwhile, the proposed method reconstructs missing luminance with aligned unsaturated focus pixel image first, and thus, the luma-recovered image provides the cues for accurate color fusion. The experimental results show that the proposed method not only accurately restores fine details in saturated areas, but also produce ghost-free high-quality HDR images without pre-alignment. [ABSTRACT FROM AUTHOR]

A new dichromatic illuminant estimation method using a deep neural network is proposed. Previous methods based on the dichromatic reflection model commonly suffer from inaccurate separation of specularity, thus being limited in their use in a real-world. Recent deep neural network-based methods have shown a significant improvement in the estimation of the illuminant color. However, why they succeed or fail is not explainable easily, because most of them estimate the illuminant color at the network output directly. To tackle these problems, the proposed architecture is designed to learn dichromatic planes and their confidences using a deep neural network with novel losses function. The illuminant color is estimated by a weighted least mean square of these planes. The proposed dichromatic guided learning not only achieves compelling results among state-of-the-art color constancy methods in standard real-world benchmark evaluations, but also provides a map to include color and regional contributions for illuminant estimation, which allow for an in-depth analysis of success and failure cases of illuminant estimation. [ABSTRACT FROM AUTHOR]

Human health is recently affected by several factors in which food contamination is one of the most dangerous elements that damage directly on our bodies. In this study, we provided a novel approach for the rapid detection of Salmonella sp. at the molecular level using the response of Saccharomyces cerevisiae's vacuoles. First, an augmentation of vacuoles intensity was observed by confocal microscopy after treating Salmonella strains with yeast cells. Second, the vacuolar enzymes were isolated and then analyzed by two‐dimensional electrophoresis for the screening of specific biomarkers. After that, various recombinant yeasts containing exclusive biomarkers were constructed by fusing these biomarkers with several fluorescent proteins. Finally, the recombinant strains showed the ability to detect Salmonella strains specifically by appropriate fluorescent signals from 20 CFU/mL after 15 Min of exposure. [ABSTRACT FROM AUTHOR]

Abstract Introduction The demand for treatment of hyperpigmentation disorders are on the rise. Artemisia capillaris is a traditional herbal plant widely used in skin protective remedies. In the present study, the inhibitory effect of Artemisia capillaris ethanol extract on the production of melanin is examined, and the active compound was isolated from the crude extract and identified. Methods The structure of the purified active compound of A. capillaris ethanol extract (ACE) was elucidated by NMR spectroscopy. ACE at the concentration of 6.25, 12.5, 25, and 50 μg/ml and active compound at the concentration of 37.5, 75, and 150 μg/ml were treated alpha-melanocyte stimulating hormone (α-MSH) induced in B16F10 melanoma cells. Melanin contents, tyrosinase activity, and protein expression of melanogenesis-related proteins were analyzed in ACE or active compound treated or untreated control. Results ACE significantly inhibited melanogenesis induced by α-MSH and tyrosinase activity without cell cytotoxicity in a dose-dependent manner. Western blot demonstrated that ACE downregulated the expression of melanocyte-specific proteins such as tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2, which catalyzes the rate-limiting oxidation of tyrosine to melanin. The active compound was finally identified as leukodin. It inhibited melanin pigment synthesis and tyrosinase activity in B16F10 melanoma cells without cytotoxicity. In addition, the leukodin decreased TRPs expression in a dose-dependent manner. Conclusions Bioactivity-guided fraction identified leukodin is the active compound in ACE extract. Leukodin suppressed melanin synthesis through inhibition of the expression of melanogenic enzymes. [ABSTRACT FROM AUTHOR]

Objectives: We intended to identify the predictive abilities of recently published transplant-specific prognostic scoring systems in patients with myelodysplastic syndrome (MDS) receiving haploidentical transplantation. Methods: The outcomes of 73 patients with MDS receiving haploidentical transplantation were analyzed, according to the MTPSS, the TRI, and the CIBMTR scoring systems. Results: The median age of patients at transplantation was 50 (range, 19-69) years. The IPSS-R cytogenetic risks of very good/good, intermediate, and poor/very poor were, respectively, observed in 35 (48.0%), 25 (34.2%), and 13 (17.8%) patients, including 4 (5.5%) with a monosomal karyotype. Pretransplant treatment failure and high (≥3) HCT-CI were observed in 30 (41.1%) and 35 (48.0%) patients, respectively. With survivor's median follow-up of 42.3 months, the overall survival rate at 4 years of all patients was 65.5% (95% CI, 52.4-75.9). The MTPSS (100%, 77.3%, 62.5%, and 42.0% at 4 years; P = .02) and the TRI (100%, 79.9%, 76.0%, and 17.1% at 4 years; P < .01) differentiate proportionally overall survival rates according to their 4 risk groups, whereas the CIBMTR scoring system did not (P = .17). Conclusions: Our results suggest the potential ability of the MPTSS and the TRI as prognostic tools for patients with MDS receiving haploidentical transplantation. [ABSTRACT FROM AUTHOR]

Podoplanin+ cells on the cellular activities of the leukemic cells, such as apoptosis and cell proliferation, in addition to the expression of podoplanin in leukemic cells, were investigated. Due to the fact that genetic abnormalities are the primary cause of leukemogenesis, the overexpression of the fibromyalgia-like tyrosine kinase-3 gene in colony forming units was also examined following cell sorting. Podoplanin+ cells were found to play a protective role against apoptosis in leukemic cells and to promote cell proliferation. Tumor-associated antigens, including Wilms' tumor gene 1 and survivin, were increased when leukemic cells were co-cultured with podoplanin+ cells. In combination, the present results also suggest that podoplanin+ cells can function as stromal cells for blast cell retention in the AML tumor microenvironment. [ABSTRACT FROM AUTHOR]

Purpose: The development of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) deteriorates patients' quality of life. This study aimed to analyze the prevalence, clinical features, risk factors and prognostic factors of BOS. Materials and Methods: This retrospective study included patients who underwent allogeneic HSCT from January 2002 to December 2008 and survived for =100 days after transplantation. Results: Of 860 patients who survived for =100 days, 36 (4.2%) met the diagnostic criteria. The duration of BOS development after transplantation was 466.00 (284.00-642.75) [median (interquartile range)] days. The risk factor for the development of BOS was peripheral blood as the stem cell source with a hazard ratio (HR) of 2.550 [95% confidence interval (CI): 1.274-5.104, p=0.008]. In multivariate analysis, pretransplant FEV1/FVC (HR: 0.956, 95% CI: 0.921-0.993, p=0.020) and time from HSCT to diagnosis of BOS (HR: 0.997, 95% CI: 0.994-0.999, p=0.009) were independent prognostic factors associated with mortality. Conclusion: Peripheral blood as a stem cell source is a risk factor for the development of BOS. A decreased pretransplant FEV1/ FVC and shorter duration of time from transplantation to diagnosis of BOS are poor prognostic factors for BOS. [ABSTRACT FROM AUTHOR]

Purpose: Posaconazole is a second-generation triazole with a broad spectrum. However, there is a lack of data to support a significant role for posaconazole in the treatment of invasive fungal infection (IFI), especially in Korea. Until recently, posaconazole was available only through the Korean Orphan Drug Center. This study was designed to review the use of posaconazole at a single-center in Korea. Materials and Methods: Data from patients who received posaconazole treatment at Catholic Blood and Marrow Transplantation Center were retrospectively reviewed between January 2007 and September 2012. Results: A total of 11 cases (3 males and 8 females, median age 52 years) received posaconazole. Five patients were given the drug for mucormycosis, two for invasive aspergillosis, and four for unspecified IFI for which galactomannan (GM) assays were negative. The treatment duration ranged from 4-250 days. Three patients received posaconazole for management refractory IFI, two for intolerance of previous antifungal therapy, and six for long-term maintenance treatment. The overall successful response rate to posaconazole was 55% (six of eleven patients). Five of eleven patients died during the study period. However, only one death was attributed to the progression of IFI. None of the patients discontinued posaconazole therapy due to adverse events. Conclusion: Posaconazole is an attractive oral antifungal agent for salvage treatment of IFI, particularly upon diagnosis of mucormycosis or in cases in which mucormycosis cannot be ruled out due to a negative GM. [ABSTRACT FROM AUTHOR]

The role of the Epstein–Barr virus (EBV) in the pathogenesis of extranodal natural killer/T-cell lymphoma (ENKTCL), and its resistance to chemotherapy raises the possibility of antiviral therapeutic strategies. The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of antiviral treatment using pegylated interferon alpha-2a (pIFN α-2a) as an adjunct to induction and maintenance therapy in patients with ENKTCL. A total of seven patients with newly diagnosed EBV-positive ENKTCL were enrolled. Pegylated IFN α-2a was administered during induction chemoradiotherapy. If patients achieved a partial or complete response (PR or CR, respectively), high-dose chemotherapy with autologous stem cell transplantation (HDT/SCT) was given. After transplantation, maintenance therapy included pIFN α-2a for 3 years. Of the patients available for evaluation, all achieved a CR or PR after induction therapy but one patient relapsed before HDT/SCT. The event free survival and overall survival at 3 years were 50.0 ± 20.4% and 66.7 ± 19.2%, respectively. The 3-year disease-free survival after transplantation of the patients that received maintenance therapy was 80.0 ± 17.9%. The results of this pilot study indicated that pIFN α-2a containing induction and maintenance therapy was feasible and effective for ENKTCL. [ABSTRACT FROM AUTHOR]

Osteolytic lesions with activated osteoclast (OC) and suppressed osteoblast (OB) activity are characteristics of myeloma bone lesion. Recently, it has been shown that bortezomib treatment enhances OB function. To evaluate the effect of bortezomib on myeloma bone lesions, we performed bone scans, where increased uptake of the radiopharmaceutical by OBs is associated with re-building activity. Bortezomib treatment markedly enhanced bone metabolic activity and increased alkaline phosphatase levels, and decreased monoclonal protein levels. These findings suggest that bortezomib has potent anti-myeloma activity and bone-protecting effects, with enhanced OB function. [ABSTRACT FROM AUTHOR]

Patients with thrombocytopenia caused by various neoplastic and primary bone marrow diseases are susceptible to major hemorrhage. There are few reports addressing the incidence and outcome of gastrointestinal (GI) bleeding in patients with aplastic anemia characterized by long-standing thrombocytopenia. We sought to retrospectively determine the incidence, etiology, clinical outcomes, and risk factors associated with overt GI bleeding in patients with aplastic anemia. We analyzed the medical records of 508 patients with aplastic anemia after excluding patients below 15 years of age or those who underwent stem cell transplantation between January 1, 2002, and December 31, 2007. A total of 32 patients developed overt GI bleeding during this period. We evaluated the site, etiology, outcomes, and major risk factors in these patients who developed GI bleeding episodes. The incidence of GI bleeding was 6.3% (32 of 508 patients) in adult patients with aplastic anemia. The incidence increased to 12.6% (28 of 222 patients) in patients with severe disease. One patient died from massive GI bleeding. Bleeding sites included the esophagus (two patients, 6.3%), stomach (five, 16.3%), duodenum (two, 6.3%), small intestine (five, 15.6%), large intestine (seven, 21.6%), and unknown site (11, 34.4%). Lower GI bleeds mainly caused by neutropenic enterocolitis (NEC) and solitary ulcer developed more frequently than upper GI bleeds. The major risk factors for GI bleeding included old age (P = 0.004, odds ratio (OR) = 1.039), severe aplastic anemia (P < 0.001, OR = 11.934), non-response to therapy (P = 0.001, OR = 5.652), and major bleeding history in another organ (P < 0.001, OR = 6.677). Overt GI bleeding in patients with aplastic anemia more frequently develops in the lower tract than in the upper tract. The risk of GI bleeding is higher in patients with the following risk factors: older age, severe disease, poor response to treatment, and major bleeding history in another organ. [ABSTRACT FROM AUTHOR]

The article reports on a study identifying risk factors that affect the impact of imatinib on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). The study says that the identification of subgroups of Ph-positive ALL transplants at high risk of relapse can be allowed by prospective assessment of the extent of minimal residual disease reduction after the first 4-week imatinib therapy.

Abstract  The gastrointestinal (GI) tract is the major target site of the graft-versus-host disease (GVHD). Whether endoscopic findings can predict the histological diagnosis and degree of severity in GVHD remains controversial. We investigated the degree of correlation between endoscopic and histological findings, and evaluated the impact of endoscopic examination on clinical decision in GVHD management. This study was conducted as a retrospective single-center study. One hundred and one patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and at the risk of GI GVHD were referred for endoscopic evaluation. Endoscopic images and histology were reviewed to diagnose and grade in a blind fashion, and the histological findings were used as the “gold standard” for diagnosis. Endoscopic findings revealed a significantly positive association with histological abnormalities of GVHD (odds ratio [OR] = 33.6, 95% CI 4.3–261.1), and the sensitivity and specificity were 98 and 44%, respectively. The kappa coefficient for agreement between the endoscopic and histological grading was 0.423 (p-value  [ABSTRACT FROM AUTHOR]

Background: In this study, the effectiveness and safety of combining gemtuzumab ozogamicin (GO) with an abbreviated schedule of standard induction chemotherapy were assessed in 37 patients (aged ≥55) yr with previously untreated acute myeloid leukemia (AML). Methods: GO was administered at a dose of 6 mg/m2 as a single 2-h intravenous infusion on day 1. Following GO, an abbreviated schedule of induction chemotherapy consisting of idarubicin (12 mg/m2/d, days 2–4), and N4-behenoyl-1- β-arabinofuranosyl cytosine (300 mg/m2/d, days 2–6) was given. Results: Thirty-seven patients were treated with GO in combination with chemotherapy. Complete remission (CR) and CR with incomplete platelet recovery were achieved in 28 patients (75.7%) and one patient (2.7%) respectively. Two patients (5.4%) died during induction and two patients (5.4%) with grade 4 treatment emergent adverse effects during chemotherapy did not complete induction chemotherapy. The majority of toxicities were mild and manageable. Severe myelosuppresion was universal with significantly prolonged thrombocytopenic period. In total, 25 patients who received consolidation treatment, 19 patients remain alive at the time of analysis. Thirteen patients had undergone hematopoietic stem cell transplantation, three are preparing for transplantation and seven are receiving their consolidation chemotherapy course. Conclusion: Although only a relatively small number of cases were included in this preliminary study and the follow-up duration was short, frontline GO in combination with attenuated conventional chemotherapy was found to be effective and feasible in elderly patients with AML. [ABSTRACT FROM AUTHOR]

Objectives: Imatinib (Glivec, STI571) has been successfully used in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome (Ph). We used imatinib interim therapy for four consecutive patients with newly diagnosed Ph+ acute myeloid leukemia (AML). We monitored the patient status for minimal residual disease by real-time quantitative polymerase chain reaction. Methods and results: Imatinib was administered on an interim schedule after each chemotherapy course. After the first imatinib cycle, all patients remained in sustained complete hematologic remission (CHR) with a decrease in the breakpoint cluster region of the Abelson oncogene locus transcript. All patients received a second imatinib cycle following consolidation and showed sustained CHR, including two cases with complete molecular remission. All cases underwent hematopoietic stem cell transplantation (HSCT) in favorable condition, and are still alive with a leukemia-free status at 6, 6, 9, and 25 months after HSCT. Conclusions: As a first-line interim therapy, imatinib appears to be a useful treatment strategy to provide a bridge to HSCT in patients with Ph+ AML. Further studies with a larger patient population and longer follow-up are needed for accurate assessment of the impact of imatinib on the long-term outcome of transplantation for patients with Ph+ AML. [ABSTRACT FROM AUTHOR]

The proteasome inhibitor, bortezomib, has antimyeloma activity even in myeloma cells refractory to multiple prior treatments. The most commonly reported adverse events in patients receiving bortezomib are sensory neuropathy, thrombocytopenia and gastrointestinal events. We report a patient with myeloma who developed pseudomembranous colitis after bortezomib treatment. Bortezomib has the boronic acid moiety which improves the specificity of proteasome inhibition and can be used as non-β-lactam-based β-lactamase inhibitors. This case indicates that gastrointestinal toxicities by bortezomib may be caused, in part, as a result of change in the colonization of colonic microflora. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The proteasome inhibitor, bortezomib, has anti-myeloma activity even in myeloma cells refractory to multiple prior treatments. Bortezomib blocks the production of nuclear factor- κB (NF κB)-mediated pro-inflammatory cytokines. We report a patient with myeloma who developed a cutaneous leucoclastic vasculitis (LV) after bortezomib treatment. The patient with LV exhibited a marked increase in serum levels of IL-6, TNF- α, and C-reactive protein (CRP). Bortezomib administration may enhance the release of pro-inflammatory cytokines, which might play a role in bortezomib-induced cutaneous LV. [ABSTRACT FROM AUTHOR]

We report a case of pure red cell aplasia (PRCA) subsequent to an allogeneic bone marrow transplantation with a major ABO mismatch, which was resistant to the standard treatment options such as plasma exchange, erythropoietin and changes in the immunosuppressive treatment. Accordingly, two cycles of Rituximab therapy were administered without success. The patient had a chronic graft-vs.-host disease of the liver, which meant that an additional donor leukocyte infusion could not be introduced. Instead, purified CD34+ cells were administered after fludarabine and antithymocyte globulin therapy. As a result, the PRCA was resolved and the antidonor isohemagglutinin titer became undetectable. [ABSTRACT FROM AUTHOR]

This retrospective study compared the results of reduced-intensity conditioning stem cell transplantation (RIST) and a conventional myeloablative regimen (CST) followed by allogeneic peripheral blood stem cell transplantation. In this respect, 63 RISTs and 41 CSTs were performed at 5 transplantation centers in Korea between April 1998 and December 2002. The RIST group had more adverse pretransplant characteristics. More aggressive diseases, like acute myeloid or lymphoblastic leukemia, were included in the CST group, while the RIST group included more indolent diseases, like chronic myeloid leukemia or myeloma (p < 0.001). The incidence of acute graft-versus-host disease (GVHD) grades 2–4 was 29.1 and 57.9% for the RIST and CST groups, respectively (p = 0.010), yet the incidence of chronic GVHD was similar in the two groups (57.4 vs. 71.9%). With a median follow-up of 13 months (0.5–61 months, 17 months in 52 survivors), the 3-year overall (OS) and disease-free survival (DFS) was similar in the RIST and CST groups (p = 0.965 for OS, p = 0.545 for DFS). In a multivariate analysis, RIST (p = 0.010), good performance status (p = 0.006) and a higher CD34+ cell dose (p = 0.008) were all identified as independent favorable prognostic factors for OS. Accordingly, in the current study, RIST produced equivalent or acceptable results compared with CST in terms of OS. Therefore, a prospective randomized trial of RIST and CST is warranted. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cho SG, Koh YB, Chang HS, Park G, Kang CS, Park JW, Min WS. Successful treatment with splenectomy and interferon alpha against recurred hemophagocytic syndrome in remission state of anaplastic large cell lymphoma following high-dose therapy and autologous peripheral blood stem cell transplantation.Eur J Haematol 2005: 74: 259–262.© Blackwell Munksgaard 2005.A 25-yr-old man had been diagnosed as having CD30+ anaplastic large cell lymphoma associated with hemophagocytic syndrome (HS). He received aggressive frontline chemotherapies and consolidation with autologous peripheral blood stem cell transplantation (PBSCT) following high-dose chemotherapy combined with splenic irradiation (720 cGy in fraction of 180 cGy). However, HS recurred on day 50 of PBSCT without radiologic evidence of lymphoma relapse. On day 56 of PBSCT, splenectomy was performed and pathology showed massive sinusoidal infiltration of histiocytes. On day 68 of PBSCT, administration of interferon alpha was started and maintained for 24 months. HS was completely resolved and he has been alive well and in complete remission (CR), 60 months after initial diagnosis. [ABSTRACT FROM AUTHOR]

Lee JW, Soung YH, Kim SY, Park WS, Nam SW, Min WS, Kim SH, Lee JY, Yoo NJ, Lee SH. Mutational analysis of theARAFgene in human cancers. APMIS 2005;113:54–7.Deregulation of RAS signal transduction has been implicated in the malignant growth of human cancer cells. TheBRAFgene, encoding a RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers, raising the possibility that other RAF family members might be mutated in human cancers. In this study we analyzed the genomic DNAs for the detection of somatic mutations of theARAFgene in 60 human cancer cell lines and 323 primary human cancer tissues, including colorectal carcinomas, gastric carcinomas, ovarian tumors and acute leukemias. The MOLT-4 leukemia cell line was found to harbor anARAFgene mutation resulting in an amino acid substitution (A451T) at the activation segment in the kinase domain of ARAF. In the cancer tissues we could not detect anyARAFgene mutation. Our data indicate that, in contrast to theBRAFgene, theARAFgene is rarely mutated in human cancers, and suggest that alterations of the RAS pathway byARAFgene mutation may not play an important role in the pathogenesis of human cancers. [ABSTRACT FROM AUTHOR]

Objective The efficacy and tolerability of paroxetine in the treatment of depressive disorders is well known, however, its efficacy and safety for the treatment of depression in patients with cancer has been poorly studied. Therefore this study was aimed at evaluating the efficacy and tolerability of paroxetine in the treatment of depressed patients with haematological malignancy (HM). Method Fifty-two patients with major depressive disorder (MDD) based on DSM-IV criteria along with comorbid HM were allotted to an 8 week trial with a flexible-dose regime of paroxetine in combination with their chemotherapy or supportive pharmacotherapy. The treatment response was assessed at baseline, week 2, week 4 and week 8 with the 17-item Hamilton rating scale for depression (HAM-D17), the Montgomery Åsberg depression rating scale (MADRS) and the clinical global impression-severity (CGI-S). Side effects were collected with reported adverse events and laboratory tests throughout the study period. Results 44.2% of 52 patients completed the 8 week trial. Scores on the HAM-D17, MADRS and CGI-s (last observation carried forward, LOCF) at baseline were significantly reduced with a mean reduction of 30.5%, 32.8% and 39.1%, respectively, after 8 weeks treatment with paroxetine. Conclusion In this preliminary study, paroxetine was found to be effective and moderately tolerated in the treatment of depressed patients with HM, and the present study calls for a controlled study in this field to extend and form a framework on the psychopharmacological data in this field. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]