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Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.

Background: Hepatitis C virus (HCV) in diffuse large B-cell lymphoma (DLBCL) is associated with a higher prevalence and distinctive clinical characteristics and outcomes. Methods: A retrospective analysis of adult DLBCL patients from 2011 to 2015 was studied. Results: A total of 206 adult DLBCL were enrolled with 22 (10.7%) HCV-positive patients. Compared to HCV-negative patients, the HCV-positive group had a poor performance status (p = 0.011), lower platelet count (p = 0.029), and higher spleen and liver involvement incidences (liver involvement, p = 0.027, spleen involvement, p = 0.026), and they received fewer cycles of chemotherapy significantly due to morbidity and mortality (p = 0.048). Overall survival was shorter in HCV-positive DLBCL (25.3 months in HCV-positive vs. not reached (NR), p = 0.049). With multivariate analysis, poor performance status (p &lt, 0.001), advanced stage (p &lt, 0.001), less chemotherapy cycles (p &lt, 0.001), and the presence of liver toxicity (p = 0.001) contributed to poor OS in DLBCL. Among HCV-positive DLBCL, the severity of liver fibrosis was the main risk factor related to death. Conclusion: Inferior survival of HCV-positive DLBCL was observed and associated with poor performance status, higher numbers of complications, and intolerance of treatment, leading to fewer therapy. Therefore, anti-HCV therapy, such as direct-acting antiviral agents, might benefit these patients in the future.

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma, and the disease course is often aggressive with poor prognosis outcomes. PCNSL undergoes germinal center reactions and impairs B-cell maturation. However, angiogenesis is also involved in the tumorigenesis and progression of PCNSL. This study investigated the effects of the tumor microenvironment and angiogenesis-associated genomic alterations on the outcomes of PCNSL. The analysis also evaluated the influence of treatment modality and timing on PCNSL survival using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and disease outcomes with a small sample of measurements and structural models. A total of 19 immunocompetent PCNSL samples were analyzed by exome sequencing. Our results suggest that the timing of radiotherapy and mutations of ROBO1 and KAT2B are potential indicators of PCNSL outcomes and may be affected by baseline characteristics such as age and sex. Our results also showed that patients with no mutations of ROBO1 and KAT2B, SubRT subgroup showed favorable survival outcomes compared with no SubRT subgroup in short-term follow-up. All SubRT patients have received high-dose methotrexate induction chemotherapy in the initial treatment. Therefore, initial induction chemotherapy combined with subsequent radiotherapy might improve survival outcomes in PCNSL patients who have no ROBO1 and KAT2B somatic mutations in short-term follow-up. The overall findings suggest that the tumor microenvironment and angiogenesis-associated genomic alterations and treatment modalities are potential indicators of overall survival and may be affected by the baseline characteristics of PCNSL patients.

Intensive efforts have been undertaken in the fields of prevention, diagnosis, and therapy of lung cancer. Fucoidans exhibit a wide range of biological activities, which are dependent on the degree of sulfation, sulfation pattern, glycosidic branches, and molecular weight of fucoidan. The determination of oversulfation of fucoidan and its effect on anti-lung cancer activity and related signaling cascades is challenging. In this investigation, we used a previously developed fucoidan (SCA), which served as a native fucoidan, to generate two oversulfated fucoidan derivatives (SCA-S1 and SCA-S2). SCA, SCA-S1, and SCA-S2 showed differences in compositions and had the characteristic structural features of fucoidan by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The anticancer properties of SCA, SCA-S1, and SCA-S2 against human lung carcinoma A-549 cells were analyzed in terms of cytotoxicity, cell cycle, Bcl-2 expression, mitochondrial membrane potential (MMP), expression of caspase-3, cytochrome c release, Annexin V/propidium iodide (PI) staining, DNA fragmentation, and the underlying signaling cascades. Our findings indicate that the oversulfation of fucoidan promotes apoptosis of lung cancer cells and the mechanism may involve the Akt/mTOR/S6 pathway. Further in vivo research is needed to establish the precise mechanism whereby oversulfated fucoidan mitigates the progression of lung cancer.

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen species (ROS) levels. The loss of NRF2 expression in OCs reduced bone mass via the RANK/RANKL pathway and other downstream signaling pathways that affect osteoclastogenesis. The NRF2 level in OBs could interfere with interleukin (IL)-6 expression, which is associated with bone metabolism and myeloma cells. In addition to direct impact on OCs and OBs, the activity of NRF2 on myeloma cells and mesenchymal stromal cells influences the inflammatory stress/ROS level in these cells, which has an impact on OCs, OBs, and osteocytes. The interaction between these cells and OCs affects the osteoclastogenesis of myeloma bone lesions associated with NRF2. Therefore, we have reviewed the effects of NRF2 on OCs and OBs in MBDs.

During the progression from hepatitis to fibrosis, cirrhosis, and liver failure, the accumulation of stressed/damaged hepatocyte elements associated with liver inflammation is critical. The causes of hepatocyte injuries include viral hepatitis infections, alcoholic hepatitis, and non-alcoholic fatty liver disease. Hepatocyte-derived extracellular vesicles (Hep-EVs) released from stressed/damaged hepatocytes are partly responsible for liver disease progression and liver damage because they activate non-parenchymal cells and infiltrate inflammatory cells within the liver, which are in turn are an important source of EVs. This cell-to-cell signaling is prevalent during inflammation in many liver diseases. Accordingly, special emphasis should be placed on liquid biopsy methods for the long-term monitoring of chronic liver diseases. In the present review, we have highlighted various aspects of current liquid biopsy research into chronic liver diseases. We have also reviewed recent progress on liquid biopsies that focus on cell-free DNA (cfDNA), long non-coding RNA (lncRNA), and the proteins in EVs as potential diagnostic tools and novel therapeutic targets in patients with viral hepatitis, fatty liver steatosis, and alcoholic liver diseases.

This is a rare but important case that the aspergillus should be considered when primary endophthalmitis happens especially in the immunocompromised patients even there is no other focus or receiving cataract surgery before. In most scenario, endogenous Aspergillus endophthalmitis results from disseminative aspergillosis from other organs or the patients receiving cataract surgery. Our case is unusual, because there is no other focus founded.

Nutritional assessments, including the Geriatric Nutritional Risk Index (GNRI), have emerged as prediction tools for long-term survival in various cancers. This study aimed to investigate the therapeutic strategy and explore the prognostic factors in the elderly patients (≥65 years) with diffuse large B cell lymphoma (DLBCL). The cutoff value of the GNRI score (92.5) was obtained using the receiver operating characteristic curve. Among these patients (n = 205), 129 (62.9%) did not receive standard R–CHOP chemotherapy. Old age (≥80 years), poor performance status, low serum albumin level, and comorbidities were the major factors associated with less intensive anti-lymphoma treatment. Further analysis demonstrated that a lower GNRI score (&lt, 92.5) was linked to more unfavorable clinical features. In the patients who received non-anthracycline-containing regimens (non-R–CHOP), multivariate analysis showed that a low GNRI can serve as an independent predictive factor for worse progression-free (HR, 2.85, 95% CI, 1.05–7.72, p = 0.039) and overall survival (HR, 2.98, 95% CI, 1.02–8.90, p = 0.045). In summary, nutritional evaluation plays a role in DLBCL treatment and the GNRI score can serve as a feasible predictive tool for clinical outcomes in frail elderly DLBCL patients treated with non-anthracycline-containing regimens.

This study aimed to investigate whether the progression risk score (PRS) developed from cytoplasmic immunohistochemistry (IHC) biomarkers is available and applicable for assessing risk and prognosis in oral cancer patients. Participants in this retrospective case-control study were diagnosed between 2012 and 2014 and subsequently underwent surgical intervention. The specimens from surgery were stained by IHC for 16 cytoplasmic target markers. We evaluated the results of IHC staining, clinical and pathological features, progression-free survival (PFS), and overall survival (OS) of 102 oral cancer patients using a novel estimation approach with unsupervised hierarchical clustering analysis. Patients were stratified into high-risk (52) and low-risk (50) groups, according to their PRS, a metric consisting of cytoplasmic PLK1, PhosphoMet, SGK2, and SHC1 expression. Moreover, PRS could be extended for use in the Cox proportional hazard regression model to estimate survival outcomes with associated clinical parameters. Our study findings revealed that the high-risk patients had a significantly increased risk in cancer progression compared with low-risk patients (hazard ratio (HR) = 2.20, 95% confidence interval (CI) = 1.10–2.42, p = 0.026). After considering the influences of demographics, risk behaviors, and tumor characteristics, risk estimation with PRS provided distinct PFS groups for patients with oral cancer (p = 0.017, p = 0.019, and p = 0.020). Our findings support that PRS could serve as an ideal biomarker for clinical use in risk stratification and progression assessment in oral cancer.

Background: Navitoclax (Nav) is a small-molecule inhibitor of several antiapoptotic B-cell lymphoma 2 (BCL2) family proteins, including BCL-xL, BCL2, and BCL-W. Preclinical studies have demonstrated that when administered alone, Nav can effectively induce apoptosis in various types of cancerous cells, including those isolated from patients (pts) with myeloproliferative neoplasms (MPNs). Ruxolitinib (Rux), a potent Janus kinase 1/2 inhibitor, can durably improve symptoms, splenomegaly, and overall survival in pts with myelofibrosis (MF) and is approved for the treatment of pts with primary MF in many countries, including Japan and Taiwan. However, pts can develop resistance to Rux, which may be overcome by the addition of Nav to a combination therapy regimen. An ongoing phase 2 study (NCT03222609) is assessing the safety and efficacy of Nav + Rux combination therapy in pts with MF, and a phase 1 study (NCT04041050) is evaluating the safety and pharmacokinetics (PK) of Nav monotherapy in Japanese pts with MPNs in part 1 and Nav + Rux combination therapy in Japanese and Taiwanese pts with MF in part 2. Herein we report the currently available results of this phase 1 study, the first to assess Nav treatment in Japanese and Taiwanese pts with MPNs including MF, polycythemia vera (PV), or essential thrombocythemia (ET). Methods: This phase 1, multicenter, open-label study enrolled pts ≥20 years of age with diagnosis of MPNs: MF, PV, or ET per World Health Organization classification. Eligible pts for part 1 of this study had an Eastern Cooperative Oncology Group performance status of 0 or 1 and were unable to tolerate/declined standard therapy or had MPNs that were unresponsive to standard therapy. Pts received Nav monotherapy at a starting dose of 50 mg orally once per day (QD) with a stepwise dose increase every ≥7 days to a maximum of 300 mg QD on the basis of tolerability. Per protocol, pts could receive treatment until disease progression, unacceptable toxicity, or the end of clinical benefit. Primary safety objectives included assessing the number of pts with dose-limiting toxicities (DLTs) within 28 days of Nav initiation and the number of pts with adverse events (AEs) throughout the study. DLTs included: grade (G)≥2 bleeding associated with low platelet counts of any G; bleeding requiring platelet transfusion; unexpected G≥2 toxicity requiring dose modification or delay of ≥1 week attributable to Nav; and all other G≥3 AEs considered related to Nav (exceptions: G3/4 leukopenia, G3 neutropenia, G4 neutropenia Results: As of May 2020, 6 female Japanese pts (median age: 62.5 years [range 41-79]) were enrolled in part 1 of this phase 1 study and diagnosed with the following: post-PV MF (n=1), post-ET MF (n=1), PV (n=2), and ET (n=2). All pts had received ≥1 prior therapy. Safety data are presented in the Table. The treatment duration for all 6 pts was between 4.6-24.7 weeks as of this cutoff, and all 6 pts were able to receive the maximum 300-mg dose of Nav, with no DLTs reported in any pts. No pts experienced a G≥4 AE during this period. Only 1 of 6 pts experienced a serious AE (SAE); this pt was discontinued and removed from the study on day 52 due to an SAE of epilepsy considered unrelated to Nav treatment. Five of 6 pts experienced a drug-related AE that led to study drug interruption and dose reduction, and all 5 pts remained on study and continued treatment. The current/most recent dose of Nav for all pts (excluding the pt who discontinued) was between 200-300 mg QD. No deaths were reported. Conclusions: Nav monotherapy had a tolerable safety profile in Japanese pts with MPNs enrolled in part 1 of this phase 1 study, with no DLTs reported. No clinically meaningful differences in safety were detected in this study compared with previous Nav monotherapy studies for hematologic malignancies. Preliminary PK and efficacy analyses for Part 1 are in progress, and Part 2 is ongoing with results to be reported in the presentation. Disclosures Shibayama: Celgene, Chugai, Eisai, AstraZeneca: Consultancy; Celgene, Ono, Takeda, AbbVie, Eisai, Novartis, Janssen, Chugai, Astellas, Teijin, MSD, Shionogi, Sumitomo Dainippon, Taiho, Nippon Shinyaku: Research Funding; Takeda, Novartis, Janssen, Ono, Chugai, Eisai, Kyowa Kirin, Sumitomo Dainippon, AstraZeneca, AbbVie, Daiichi Sankyo, Fujimoto, Nippon Shinyaku, Sanofi, Bristol-Myers Squibb, Pfizer, Otsuka, Mundipharma: Honoraria. Tanaka:Novartis Pharma KK, Celgene K.K: Speakers Bureau. Yeh:Amgen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees. Hsiao:AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Nuthalapati:AbbVie: Current Employment, Other: may own stock. Ono:AbbVie: Current Employment, Other: may own stock. Uehara:AbbVie: Current Employment, Other: may own stock. Okubo:AbbVie: Current Employment, Other: may own stock. Komatsu:Otsuka Pharmaceutical Co., Ltd., PharmaEssentia Japan KK, AbbVie GK, Celgene KK, Novartis Pharma KK, Shire Japan KK, Japan Tobacco Inc: Consultancy; Takeda Pharmaceutical Co., Ltd, Novartis Pharma KK, Shire Japan KK: Speakers Bureau; AbbVie: Other: member of safety assessment committee in M13-834 clinical trial.; PPMX: Consultancy, Research Funding; Meiji Seika Pharma Co., Ltd.: Patents & Royalties: PCT/JP2020/008434, Research Funding; Otsuka Pharmaceutical Co., Ltd., Shire Japan KK, Novartis Pharma KK, PharmaEssentia Japan KK, Fuso Pharmaceutical Industries, Ltd., Fujifilm Wako Pure Chemical Corporation, Chugai Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Takeda Pharmaceutica: Research Funding.

Background Hepatitis B virus (HBV) reactivation with a hepatitis flare is a common complication in lymphoma patients treated with immunotherapy and/or chemotherapy. Anti-HBV prophylaxis is suggested for non-Hodgkin lymphoma (NHL) patients undergoing rituximab therapy, even those with resolved HBV infection. Since anti-HBV prophylaxis for patients with resolved HBV infection is not covered by national health insurance in Taiwan, a proportion of these patients receive no prophylaxis. In addition, late HBV reactivation has emerged as a new issue in recent reports, and no consensus has been reached for the optimal duration of antiviral prophylaxis. Thus, the aim of our study was to investigate the incidence and outcomes of HBV reactivation in NHL patients in a real-world setting and to study the frequency of late HBV reactivation. Materials Non-Hodgkin lymphoma patients who received rituximab and/or chemotherapy at our institute between January 2011 and December 2015 and who were hepatitis B surface antigen (HBsAg)- or hepatitis B core antibody (HBcAb)-positive were reviewed retrospectively. Results A total of 388 patients were screened between January 2011 and December 2015. In total, 196 patients were excluded because HBsAg was not assessed, HBcAb was negative or not assessed, or they were not treated with immunosuppressive therapy. Finally, the retrospective study included 62 HBsAg-positive NHL patients and 130 NHL patients with resolved HBV infection (HBsAg-negative and HBcAb-positive). During a median 30.5-month follow-up period, seven patients experienced HBV reactivation, five of whom had a hepatitis flare. The incidence of HBV reactivation did not significantly differ between the HBsAg-positive patients and the resolved HBV infection population without anti-HBV prophylaxis (4.8% vs. 3.1%, P = 0.683). All patients with HBV reactivation were exposed to rituximab. Notably, late HBV reactivation was not uncommon (two of seven patients with HBV reactivation events, 28.6%). Hepatitis B virus reactivation did not influence the patients’ overall survival. An age ≥65 years and an advanced disease stage were independent risk factors for poorer overall survival. Conclusion The incidence of HBV reactivation was similar between the HBsAg-positive patients with antiviral prophylaxis and the resolved HBV infection population without anti-HBV prophylaxis. All HBV reactivation events occurred in NHL patients exposed to rituximab. Late reactivation was not uncommon. The duration of regular liver function monitoring for more than 1 year after immunosuppressive therapy or after withdrawal of prophylactic antiviral therapy should be prolonged. Determining the exact optimal duration of anti-HBV prophylaxis is warranted in a future prospective study for NHL patients treated with rituximab-containing therapy.

Hepatitis B reactivation is a common complication in lymphoma patients under immunosuppressive treatment with potentially serious and life-threating consequences. In this review, we discuss the basis of chronic Hepatitis B virus (HBV) infection, the definition and risk factors for HBV reactivation. We overview the management of HBV reactivation based on virological status and immunosuppressive regimen risk stratification. We also highlight and update information about the HBV reactivation in lymphoma patients under novel agent treatment, including newer monoclonal antibodies, small molecule inhibitors, and even chimeric antigen receptor T-cell immunotherapy.

Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma–cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These consequences affect disease outcomes, including patients’ quality of life and survival. Several studies have sought to better understand MM bone disease (MBD) through the classification of its molecular mechanisms, including osteoclast activation and osteoblast inhibition. Bisphosphonates and the receptor activator of the nuclear factor-kappa B (NF-κB) ligand (RANKL) inhibitor, denosumab, prevent skeletal-related events in MM. In addition, several other bone-targeting agents, including bone-anabolic drugs, are currently used in preclinical and early clinical evaluations. This review summarizes the current knowledge of the pathogenesis of MBD and discusses novel agents that appear very promising and will soon enter clinical development.

Since 1993, following the National Thalassemia Major Prevention Program and an increase in immigration and interracial marriages, especially in southern Taiwan, the distribution of hemoglobinopathies may have changed. This study investigates the epidemiologic transition of hemoglobinopathies. We analyzed 1870 specimens collected between 2003 and 2012 in southern Taiwan, used gap-polymerase chain reaction and PCR-restriction fragment length polymorphism-based methods, and confirmed genotypes of hemoglobinopathies by DNA sequencing. We found a 91% reduction in the incidence of thalassemia major compared with samples from between 1986 and 1995. The most common genotypes of α-thalassemia and α Hb variants were the SEA type (69.4%) and Hb Quong Sze (1.54%). The most common genotypes of β-thalassemia and β Hb variants were IVS-II-654 (46.2%) and Hb E (2.2%), respectively. Compared with studies performed in different areas of and time intervals in Taiwan, a higher prevalence of −α3.7, Hb Quong Sze, and Hb E and a lower prevalence of the SEA type were found in this study. However, the SEA type remained the most common genotype observed. In addition, an increasing number of cases with an −α3.7 type carrier, Hb Quong Sze carrier, and Gγ(Aγδβ)° were identified following a peak of interracial marriages between 2003 and 2005, reflecting a regional difference and the impact of interracial marriage. In conclusion, global migration and international marriage have changed the distribution of hemoglobinopathies in Taiwan. A more comprehensive prenatal screening for new immigrants with a longer follow-up is warranted.

Primary adrenal non-Hodgkin lymphoma is an extremely rare disease confined wholly or chiefly to extranodal involvement. We report the case of an old woman who presented with progressive malaise and was diagnosed with primary adrenal diffuse large B-cell lymphoma pathology using laparoscopic adrenalectomy. Enhanced computed tomography and positron emission tomography revealed bilateral adrenal involvement.

Somatic mutations of exon 9 of calreticulin gene (CALR) were diagnosis and prognosis importance found in patients with JAK2V617F-negative essential thrombocythemia (ET). We survey CALR and JAK2 mutations in our ET patients and study the relationship between mutations and clinical presentations. A total of 60 ET patients were enrolled in the study, and CALR mutations were studied by high resolution melting (HRM) methods and sequencing in JAK2V617F-negative group retrospectively. Clinical manifestations were reviewed retrospectively from chart records. Twenty-one CALR mutations showed eight types of specific melting curves detected by the HRM method and sequencing validation among 26 JAK2 V617F-negative patients. Compared with JAK2 mutations, patients with CALR mutations were younger and had a higher platelet count, lower white cell counts, and lower hemoglobin levels significantly (p

Multiple myeloma with clonal plasma expansion in bone marrow is the second most common hematologic malignancy in the world. Though the improvement of outcomes from the achievement of novel agents in recent decades, the disease progresses and leads to death eventually due to the elusive nature of myeloma cells and resistance mechanisms to therapeutic agents. In addition to the molecular and genetic basis of resistance pathomechanisms, the bone marrow microenvironment also contributes to disease progression and confers drug resistance in myeloma cells. In this review, we focus on the current state of the literature in terms of critical bone marrow microenvironment components, including soluble factors, cell adhesion mechanisms, and other cellular components. Transcriptional factor nuclear factor erythroid-derived-2-like 2 (NRF2), a central regulator for anti-oxidative stresses and detoxification, is implicated in chemoresistance in several cancers. The functional roles of NRF2 in myeloid-derived suppressor cells and multiple myeloma cells, and the potential of targeting NRF2 for overcoming microenvironment-mediated drug resistance in multiple myeloma are also discussed.

The aim of this study was to investigate the role of 2-fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the initial staging and prediction of bone marrow involvement in patients with newly diagnosed lymphoma. A total of 185 patients with newly diagnosed lymphoma were enrolled. All patients received PET/CT and bone marrow biopsy as part of a staging work-up. At the initial staging, 17 patients (9.2%) with occult nodal or extranodal lesions were upstaged after a review of the PET/CT studies. PET/CT was found to be useful in the differentiation of aggressive lymphoma subtypes from the indolent subtype based on higher standardized uptake value (SUV) (16.67 vs. 7.98, p

Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 μM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.

T-cell lymphomas are generally aggressive malignancies with poor prognosis. There are no standard treatment guidelines for T-cell lymphomas, and the timing of stem cell transplantation (SCT) is not well known. In this study, we investigated the outcomes of Taiwanese patients with T-cell lymphomas after SCT. We retrospectively analyzed 131 patients with T-cell lymphomas receiving SCT (autologous: 90, allogeneic: 41) from 2009 to 2014. More autologous SCT recipients were ALCL or in complete remission, and more allogeneic recipients had advanced disease. 56 patients who were sensitive to chemotherapy underwent SCT as upfront setting. The 2-year PFS and OS rates were 67.0 and 64.5%, respectively. Regarding disease status before transplantation, patients with CR1 had the best outcomes. Among different subtypes, patients with natural killer/T-cell lymphomas showed the worst outcomes, with 2-year OS rate of 23.5%. The OS rates for the other three major subtypes were as follows: 72.9% for ALCL; 75.0% for AITL; and 51.4% for PTCL-NOS. For more rare subtypes, such as ATLL and SPTCL, data from our study show that SCT can be beneficial. We concluded that upfront autologous SCT is feasible and effective for patients with low PIT, and disease status at transplant is the strong predictor of outcome.

This study aimed to investigate the treatment strategy, prognostic factors, and risk factors of early death in elderly patients (age ≥ 65 years) with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Data from elderly patients diagnosed with DLBCL between 2008 and 2014 were collected for analysis. Patients who were younger and had a better performance status were more likely to receive intensive frontline treatment. The median progression-free survival (PFS) and overall survival were 15 and 21 months, respectively. Anthracycline-containing chemotherapy achieved a higher remission rate and showed a trend towards better overall survival but a higher risk of severe neutropenia. Multivariate analysis revealed that very old age (≥81 years), a high-risk age-adjusted international prognostic index (aaIPI) score, and bone marrow involvement were associated with poorer PFS and overall survival. Progression of lymphoma was the major cause of death in the study population. In addition, approximately 25% of patients died within 120 days of being diagnosed. The risk factors for early mortality included very old age, a high-risk aaIPI score, and bone marrow involvement. The appearance of symptoms or signs of tumour lysis syndrome at diagnosis was associated with a trend towards early death.

Urothelial carcinoma is the most discussed form of bladder cancer. However, there are also other histological subtypes, such as adenocarcinoma, which have different presentations, treatment strategies, and prognosis. Primary adenocarcinoma of the urinary bladder can be classified as urachal adenocarcinoma and nonurachal adenocarcinoma. The average age of patients with urachal adenocarcinoma is about one decade younger than those with the nonurachal subtype, and the prognosis of urachal adenocarcinoma is better. Complete surgical resection is the standard treatment, but adjuvant therapy is always needed due to the high relapse rate. Due to the rareness, research about this malignancy is limited. Herein, we report two cases with different primary adenocarcinomas of the urinary bladder and perform a literature review.

Posterior reversible encephalopathy syndrome (PRES) is a syndrome related to endothelial dysfunction and disorder in cerebral autoregulation. The clinical manifestations include seizures, headache, mental alteration, and visual disturbance. The causes of PRES are diverse and include renal failure, transfusion, transplantation, endocrine disorders, autoimmune diseases, and cytotoxic and immunosuppressive agents. Various anti-cancer drugs such as gemcitabine and platinum can also cause PRES, and a few case reports have discussed the effect of immunotherapy on PRES. In this article, we present a case who developed PRES after receiving gemcitabine, cisplatin, and pembrolizumab. We also review previous cases with gemcitabine/cisplatin- and immunotherapy-induced PRES. Most of these cases had a good clinical outcome, the resolution of neurologic signs varied from days to weeks.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

Mucosal lichen planus (MLP) is a chronic mucosal disorder that often poses a therapeutic challenge to dermatologists, dentists, and gynecologists. To relieve patients’ pain and discomfort, improve their quality of life, and achieve clinical improvement, various therapeutic approaches can be considered for this disease. Based on the current literature it is difficult to define any particular treatment as the main therapeutic modality. We aimed to systematically review the current literature for the effectiveness of available treatment modalities for MLP. All of the randomized controlled trials and systematic reviews of MLP were collected by searching Pubmed, EMBASE, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, and China National Knowledge Infrastructure. Meta-analysis was performed, if possible. Topical betamethasone valerate, clobetasol-17-propionate, and fluocinonide are effective in the treatment of oral lichen planus (OLP) when compared with placebo. Calcineurin inhibitors and topical retinoids are also beneficial treatment options. The review does not include therapies with a lower level of evidence. Topical corticosteroids are the mainstay of therapy for OLP. High-quality evidence is lacking for the treatment of lichen planus.

The Philadelphia (Ph) chromosome and/or Breakpoint cluster region-Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML). However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1%) with the classic Ph chromosome, 6 (7.2%) with a variant Ph chromosome, and 9 (10.7%) with additional chromosome abnormalities. Fifty-four (64.3%) cases harbored b3a2 transcripts, 29 (34.5%) had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first- and second-line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second-line therapy had a significant poor impact (p

Tumor lysis syndrome (TLS) is a life-threatening oncological emergency that usually occurs after cytotoxic therapy in patients with a large tumor burden, for example, patients with high-grade lymphoma or acute lymphoblastic leukemia (ALL). We report a case of a patient with ALL who spontaneously developed TLS without having undergone cytotoxic therapy. The mechanisms of spontaneous TLS are unclear, and the relationship between adenosine and cell growth/cell death is controversial. Several literature reviews have revealed that adenosine plays a role in the survival signal pathway. Although rare, our case is an example of a patient developing spontaneous TLS after adenosine treatment.

Nonadherence is common in patients with chronic myeloid leukemia (CML) and leads to treatment failure and poor outcomes. Side effects due to treatment are also common in patients with CML. However, no study has investigated the link between side effects and medication adherence for patients with CML in Taiwan. Therefore, the aim of our study was to explore the influence of side effects on medication adherence in Taiwanese patients with CML. CML in chronic-phase patients treated with breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 tyrosine kinase inhibitors were recruited. We designed a questionnaire to collect baseline patient information, medication adherence (measured using the 8-item Morisky Medication Adherence Scale), and side effects. Clinical outcomes were assessed by the 3-month early molecular response rate and the 12-month major molecular response rate. Statistical comparisons of different parameters between adherent and nonadherent groups were conducted. Fifty-eight patients were enrolled in this study, and 31% of them had poor adherence. The lack of information about treatment and medication was the major reason for poor medication adherence. Patients who were younger and unmarried were prone to poor adherence. The occurrence of side effects carried no statistically significant influence on adherence. Poor adherence resulted in a poor treatment response (lower 3-month early molecular response rate and lower 12-month major molecular response rate). Poor adherence is common in Taiwanese patients with CML. The main reason for a decrease in the adherence rate is the lack of comprehensive information about treatment and medication, particularly in young and single population. The next urgent step is to educate patients about their treatment and management of side effects to improve adherence and treatment outcome for patients with CML in Taiwan.

The synchronous existence of two different tumors in the gastrointestinal tract is uncommon. We report the case of a 75-year-old man who had a concurrent gastrointestinal stromal tumor and adenocarcinoma at the gastroesophageal junction. The two tumors arose at the same site but had distinct morphologies. The etiology of synchronous tumors is still unclear and their coexistence causes problems for the surgeon, oncologist and pathologist in terms of their diagnosis, treatment, and follow-up. We report a rare case of synchronous tumors and a review of the literature.

Resistance and intolerance to imatinib are of particular clinical relevance to Asian patients because of their lower body surface area. Dasatinib is 325-fold more potent than imatinib in inhibiting BCR-ABL in vitro and is indicated for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib. Data from a series of phase I/II research trials were analyzed to compare the efficacy, safety and pharmacokinetic profile of dasatinib 70 mg twice daily in Asian and non-Asian patients. Results from 55 Asian and 615 non-Asian patients demonstrated that the efficacy and safety of dasatinib was comparable. Dasatinib was well tolerated, with no observed toxicities exclusive to Asian patients. A higher incidence of adverse events and lower rate of response observed among Asian patients with myeloid blast phase CML reflected the aggressive nature of the disease. Analyses of noncompartmental pharmacokinetics (5 Asian and 49 non-Asian patients) and population pharmacokinetics (17 Asian and 382 non-Asian patients) were also comparable. The efficacy, safety and pharmacokinetic profile of dasatinib 70 mg twice daily is similar in Asian and non-Asian patients with CML. Dasatinib is therefore an important therapeutic option for this patient population.

Primary liver lymphoma is extremely rare. The diagnosis depends on the physician's suspicions and histological examination. We report the case of a man aged 38 years who suffered from abdominal discomfort and hypercalcemia. Sonography showed a huge, solid liver tumor, and magnetic resonance imaging showed the tumor had characteristics of hypointensity on T1-weighted and hyperintensity on T2-weighted imaging. Primary liver lymphoma was diagnosed by histological examination from biopsy. We report this rare type of liver tumor and review the clinical presentation and treatment of the disease.

Objectives The Janus kinase 2 mutation, JAK2 (V617F) , and megakaryocytic mutations, MPL (W515L/K) , have been identified and correlated with a subtype of essential thrombocythemia (ET) patients. We investigated the frequency of mutations in ET patients and analyzed the relationship with their clinical features. Methods Fifty-three ET patients were enrolled in the study. The amplification refractory mutation system was applied for the mutation survey of the JAK2 V617F , while the polymerase chain reaction with sequencing was used for the mutation survey of MPL W515L/K . Results Thirty-five (66%) patients harboring the JAK2 V617F mutation, including 3 homozygous and 32 heterozygous changes, but no MPL W515L/K mutation, were found. During follow-up, 17 (32.1%) patients suffered from documented thrombotic events, with 15 having JAK2 V617F mutations. Statistical analysis showed that patients with the JAK2 mutation had significantly higher leukocytes, hemoglobin level, and thrombotic event ( p = 0.043, p = 0.001, and p = 0.029, respectively). Thrombotic events were also significantly correlated with leukocytosis and older age. Conclusions The JAK2 V617F mutation was noted in a certain population of ET patients and correlated with leukocytosis, high hemoglobin level, and thrombosis. Therefore, detection of the JAK2 V617F mutation can affect not only the diagnosis, but also the management of ET patients.

Dihydropyrimidine dehydrogenase (DPD), which is the initial and rate-limiting enzyme of the degradation of pyrimidine base, plays an important role in the pharmacogenetic syndrome of 5-fluorouracil (5-FU). Deficiency of DPD activity leads to severe toxicities, even death, in patients after administering 5-FU. Several studies demonstrate that the molecular defects of the dihydropyrimidine dehydrogenase gene (DPYD) lead to the deficiency of DPD activity and cause this pharmacogenetic syndrome. However, polymorphic DPD activity and complex nature of the DPYD sometimes result in conflicting findings. To date, more than 40 variant alleles, including 2 splice-site mutations, 2 nonsense mutations, 5 deletion mutations, 32 missense mutations and 2 slice mutations have been reported in the coding area of the DPYD gene. The IVS14+1G>A, which leads to the skipping of the exon 14 resulting in profound DPD deficiency and severe toxicities, is the most common mutation with 5-FU toxicity in Europeans. In addition, the epigenetic factors also participate in the clinical presentations of the syndrome. Due to the fact that the regulation mechanism of DPD itself has not been clearly clarified yet, high-throughput techniques to screen the whole DPYD and the measurement of the DPD activity are war- ranted to draw a clear relationship between the phenotype and genotype for this pharmacogenetic syndrome. Screening for genetic DPYD defects, at least IVS14+1G>A, and/or the DPD activity before 5-FU therapy to protect patients from haz- ardous outcome is also suggested, especially in specific populations.

This study investigated the incidence of and risk factors for herpes zoster in patients with non-Hodgkin lymphoma (NHL) who were receiving anti-lymphoma treatment. The overall incidence density of herpes zoster was 12.21% (472/3865); 11.79% (258/2188) of the patients received conventional chemotherapy and 12.76% (214/1677) of the patients received rituximab-containing chemotherapy. For the patients who received conventional chemotherapy, the risk factors included female gender, multiple courses of chemotherapy and autologous hematopoietic stem cell transplantation. For the patients who received rituximab-containing chemotherapy, the risk factors included female gender, diabetes mellitus, multiple courses of chemotherapy, autologous hematopoietic stem cell transplantation and higher accumulated rituximab dose. The majority of the herpes zoster episodes occurred within the first two years after the diagnosis of NHL. After adjusting for the propensity score matching, rituximab-containing chemotherapy was not associated with a higher overall incidence density of herpes zoster (P = 0.155). However, the addition of rituximab to conventional chemotherapy increased the short-term risk of herpes zoster with adjusted odd ratios of 1.38 (95% confidence intervals (CI) = 1.05–1.81, P = 0.021) and 1.37 (95% CI = 1.08–1.73, P = 0.010) during the 1-year and 2-year follow-up periods, respectively.

Gastrointestinal stromal tumors (GIST) are rare soft tissue sarcomas arising primarily from mesenchymal tissue in the gastrointestinal tract and abdomen. Since there is no effective treatment in the advanced stages, the outcome is poor in such patients. Recently, imatinib mesylate, a selective tyrosine kinase inhibitor, has shown a promising effect in GIST. Hence, we report our experience on the management of advanced GIST with imatinib therapy. A total of 14 patients were enrolled in this study, including 10 males and four females (median age, 51 years). The results showed that the small intestine was the most frequent site of primary lesion, while the liver was the most frequently metastasized organ. Most of the patients experienced tolerable side effects with imatinib therapy, including edema of periorbital area and/or legs and abdominal pain. Only two mortalities were noted during follow-up. The patients clinically benefited from imatinib therapy, with one patient having a complete response, three having a partial response, and seven having stable disease. The results demonstrate promising effects of imatinib in advanced GIST.

Therapy-related myelodysplastic syndrome (MDS) is a major problem in long-term cancer survivors, therefore early detection and prevention of therapy-related secondary neoplasia is an important issue. We searched for therapy-related MDS and analyzed cytogenetic changes in 155 patients with multiple myeloma (MM) from a single institution. Of the total 155 MM patients with cytogenetic results, 7 patients showed de novo appearance of myeloid-related cytogenetic changes, and 5/7 had -7/7q-, including 3 with der(1;7)(q10;p10): 3 patients developed MDS (i.e. 2 patients with der(1;7)(q10;p10) and 1 with a complex abnormality including -5 and 7q-). Among five patients receiving more than 2 g of melphalan, three developed MDS, and two of them showed der(1;7)(q10;p10) before or at the time of MDS diagnosis. Although morphologic identification of MDS was difficult in some cases, we concluded that the presence of 7q-, specifically der(1;7)(q10;p10), during chemotherapy involving melphalan for MM patients might indicate hidden MDS status and appropriate therapeutic options should be considered for such patients.

Invasive fungal infections, a serious problem among cancer patients, are increasing in incidence, and can cause morbidity and mortality. Such infections may hinder additional treatment, especially for patients with leukemia. We report here our experiences in the management of invasive fungal infection in patients with acute leukemia. A total of 18 patients were enrolled in the study: 12 had microabscesses of the liver and/or spleen and/or kidneys; four had sinonasal infections; and two had pulmonary infections. Most of the patients (88.9%) received amphotericin B during treatment for fungal infection. Thirteen patients achieved complete response without evidence of fungal infection in follow-up. In the study, there were 11 mortalities, including five patients who died during therapy and six who later died as a result of relapse or refractoriness of the leukemia. We suggest that many patients may have a good response to antifungal therapy, and that fungal infection does not have to preclude additional chemotherapy after proper management. The state of the underlying disease has a strong impact on outcome.

We analyzed 23 patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) showing a der(1;7)(q10;p10) [hereafter der(1;7)] to identify the exact predictive factor of this cytogenetic change. Eight (34.8%) patients, including six with MDS and two with AML patients, had a previous history of genotoxic exposure, especially radiation and/or antimetabolites. Patients with der(1;7) consisted of three groups: one third of patients had a previous history of genotoxic agents, one third had additional cytogenetic changes at the time of MDS/AML diagnosis without previous exposure history, and the remaining one third had neither a previous exposure history nor additional cytogenetic changes. The current study demonstrated that the poor outcome of MDS/AML with der(1;7) is caused by the high frequency of associated risk factors (i.e., previous history of genotoxic exposure, the presence of additional cytogenetic changes, or both). Identification of prognostic disadvantage might be required for applying the appropriate strategy in managing MDS/AML patients with rare der(1;7) abnormality.

Primary mediastinal germ-cell tumors (GCTs) without gonadal involvement are rare and can be divided into benign mature teratoma and malignant seminoma or nonseminoma. We describe our experience of malignant mediastinal GCTs and compare the presentations and outcome with those of benign teratomas. Four malignant GCTs (1 seminoma, 1 choriocarcinoma, and 2 yolk-sac tumors) have been treated in our hospital. All patients were men with obvious symptoms before diagnosis. The patient with seminoma was treated with surgery and radiation, while those with nonseminoma tumors were treated with chemotherapy and/or surgery. Two patients died, one with extended pulmonary metastasis and the other with relapsed disease and high levels of tumor markers. Compared with the nine cases of benign teratomas, the four malignant GCTs showed overwhelming male dominance, advanced symptoms at presentation, and poor outcome. These cases highlight the important role of disease staging and tumor-marker levels in malignant GCTs, and suggest that new treatment strategies for malignant GCTs await further investigation.

Pure red cell aplasia (PRCA) is a complication of ABO-incompatible allogeneic stem cell transplantation. The mechanism is not well known, although the isoagglutinin titer before transplantation or cyclosporine use is considered to be the cause. Patients with this complication require more blood transfusions than those without it. There is no standard treatment. We report two cases of PRCA after allogeneic peripheral blood stem cell transplantation that were successfully treated with plasma exchange and low-dose steroid.

This retrospective study compared the outcomes in 32 adult patients with hematologic diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, severe aplastic anemia) who received allogeneic bone marrow transplantation (BMT, n = 14; median age, 28 years) or allogeneic peripheral blood stem cell transplantation (PBSCT, n = 18; median age, 29 years) from human leukocyte antigen-identical sibling donors. Median follow-up was 58 months in BMT recipients and 18 months in PBSCT recipients. Neutrophil (median, Day 8 vs Day 13, p < 0.001) and platelet engraftment (median, Day 9 vs Day 17, p < 0.001) was faster in the PBSCT group than in the BMT group. Patients receiving PBSCT required less platelet transfusion than those receiving BMT (median, 54 units vs 144 units, p < 0.001), but there was no significant difference in red cell transfusion. At 100 days, there was no difference in the incidence of acute graft-versus-host disease (GVHD) (42.9% vs 33.3%, p = 0.72) or grade II-IV acute GVHD (14.3% vs 5.6%, p = 0.57), and there was no difference in the cumulative incidence of chronic GVHD (20% vs 33.3%, p = 0.67). No chronic GVHD was noted in any relapsed patients (BMT, 5; PBSCT, 3), and no patients with chronic GVHD during follow-up had a relapse. Relapse was the most frequent cause of death in both groups (BMT, 5/9, 55.6%; PBSCT, 3/4, 75%; p = 0.25); all relapses occurred within 1 year after transplantation. Overall survival was significantly better in the PBSCT group (35.7% vs 77.8%, p = 0.029), but this difference was lost if only hematologic malignancies were analyzed (30.8% vs 63.6%, p = 0.20). Our results are similar to those reported previously, with faster neutrophil and platelet engraftment and less severe acute GVHD and extensive chronic GVHD with PBSCT. Allogeneic PBSCT is a feasible and beneficial alternative to allogeneic BMT in adult hematologic disease.