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Background In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. Patients and methods This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. Results A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). Conclusions Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine., Highlights • This is the largest pharmacogenetic study of gemcitabine-based breast cancer treatment in a prospective clinical trial. • Several genetic polymorphisms in CMPK1, SLC29A1, and TLE4 were associated with 6-month PFS rate and the duration of PFS. • The result of this study may contribute to the personalized treatment of breast cancer.

Numerous studies have shown that osteoporosis is common in kidney transplant recipients. However, the change in bone mineral density after kidney transplantation (KT) is not fully understood.Thirty-nine kidney transplant recipients with bone densitometry at pretransplant and 24 months after KT were reviewed.The recipients' median age (44.5 ± 10.7 years) and dialysis duration before KT (4.2 ± 3.4 years) were recorded. The T-scores of the lumbar spine and femur neck at 24 months after KT were positively associated with the respective pretransplant T-score (P .001 in the lumbar spine and P .001 in the femur neck). However, the T-score after KT did not show significant change (P = .680 in lumbar spine, P = .093 in femur neck). Changes in the T-scores of the lumbar spine and femur neck over 24 months (delta T-score) were negatively associated with the respective pretransplant T-scores (P = .001 in lumbar spine, P = .026 in femur neck). Changes in the T-scores of the lumbar spine and femur neck over 24 months (delta T-score) were also associated with the pretransplant T-scores after the adjustment of other variables.The change of bone mineral density was related with pretransplant bone mineral density. Careful follow-up of bone densitometry for KT recipients was needed.

Besides the initial description of IgG4-related pancreatic disease, other sites are now commonly involved. However, occurrence of IgG4-related disease is rare in organ transplanted patients. A 57-year-old man who received a kidney transplantation presented with recurrent dyspnea on exertion. A computed tomography scan of the chest revealed bilateral interlobular septal thickening and multiple tubular and branching small nodular lesions in the right upper lobe, and mass-like consolidation of the left middle lobe. Despite no elevation of serum IgG4 level, a percutaneous core needle biopsy on consolidative mass showed interstitial fibrosis and infiltration of IgG4-positive plasma cells to be more than > 20 per high power field. After treatment with glucocorticoids and rituximab, the consolidative mass of the left middle lobe disappeared.

Extensive portomesenteric venous thrombus preventing restoration of adequate portal venous flow used to be considered a contraindication to liver transplantation. The subject was a 49-year-old male with hepatitis B cirrhosis and extensive thrombosis of portal, splenic, and superior mesenteric veins, and two large collateral vessels; one dilated and tortuous inferior to the pancreaticoduodenal vein and relevant to splanchnic venous return and the other a dilated coronary vein relevant to splenic venous return. During operation, the portal vein was anastomosed to these large collateral vessels using cryopreserved iliac vein. In conclusion, portal reconstruction with large collateral vessels in living-donor liver transplantation could be used selectively for patients with extensive portomesenteric venous thrombosis.

Arterial stiffness is associated with cardiovascular disease in end-stage renal disease (ESRD) and after kidney transplantation. We examined how kidney transplantation influences brachial-ankle pulse-wave velocity (baPWV) in ESRD patients.The prospective observational study enrolled 67 patients who underwent successful kidney transplantation. Serial baPWV and biochemical parameters were measured before surgery and 6 months, 1 year, and 2 years after transplantation.baPWV prior to kidney transplantation and 6 months, 1 year, and 2 years after transplantation was 1533 ± 261 cm/s, 1417 ± 254 cm/s, 1414 ± 285 cm/s, and 1384 ± 233 cm/s, respectively. baPWV and biochemical parameters including alkaline phosphatase, intact parathyroid hormone, and 1,25 hydroxyvitamin D improved significantly at 6 months (P .05), but there were no changes between 6 months and 2 years after transplantation. The majority of patients (73%) improved, whereas the remainder showed progression of baPWV after transplantation. Sixty-three percent of all kidney transplantation patients displayed higher baPWV than the healthy control subjects at 6 months after transplant.In the majority of patients, baPWV improved soon after kidney transplantation but overall remained higher than in the generally healthy population.

Introduction The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Material and methods Expression and function of Prx II in HCC was determined using H-ras G12V –transformed HCC cells (H-ras G12V –HCC cells) and the tumour livers from H-ras G12V –transgenic (Tg) mice and HCC patients. Results and discussions Prx II was upregulated in H-ras G12V –HCC cells and H-ras G12V –Tg mouse tumour livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1 binding site of Prx II promoter significantly reduced Prx II levels in H-ras G12V –HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumours in H-ras G12V –Tg livers. Consistent with this, knockdown of Prx II in H-ras G12V –HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth, and tumour formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumour phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of ERK pathway and expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras G12V –HCC cells and H-ras G12V –Tg livers. Conclusion Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras G12V oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.

Numerous studies have shown that vitamin D deficiency is common in end stage renal disease patients. However, change of the vitamin D deficiency after kidney transplantation is not fully understood.Twenty-five kidney transplant (KT) recipients with serum 25-hydroxyvitamin D (25D) level, 1,25-dihydroxyvitamin D (1,25D) level, parathyroid hormone (PTH) level before and 6, 12, and 24 months after transplantation were reviewed.Serum PTH level and 1,25D level showed significant changes at 6 months after transplantation, but did not show further change at 12 months. 25D level did not increase within 6 months after transplantation. However, 25D level showed gradual increase after 6 months. The proportion of recipients with 25D deficiency (10 ng/mL) was 68%, 40%, and 28% before, 12 months after, and 24 months after transplantation, respectively. Patients with vitamin D deficiency at 24 month were younger at transplantation (37.7 ± 9.6 y vs 48.2 ± 8.0 y; P = .029) and had lower 25D level before transplantation (7.96 ± 1.74 ng/mL vs 10.59 ± 4.35 ng/mL; P = .041).25D deficiency is persistent in almost kidney transplant recipients even 12 months after transplantation, although serum PTH levels decrease and serum 25D levels increase after transplantation.

Background There is controversy regarding the best method and benefit of cardiac evaluation of asymptomatic renal transplant candidates. The positive predictive value of ischemia on a noninvasive stress test was ∼5%–10% in Kidney Disease Outcomes Quality Initative (KDOQI), American Society of Transplantation (AST), and Lisbon guidelines. We compared prediction of cardiac events with the use of simple transthoracic echocardiography versus a noninvasive stress test in asymptomatic candidates. Methods We selected asymptomatic patients with good functional capacity who would be recommended a cardiac stress test by both KDOQI and AST guidelines, we excluding those with a history of cardiovascular disease. Group A (n = 124) underwent only echocardiography, and group B (n = 41) underwent echocardiography and noninvasive stress test. We measured the incidences of cardiac events and cardiac death within 3 years after transplantation. Results The mean age of group A was 39 ± 7 and group B 40 ± 5 years. Diabetic patients among groups A and B were 8.8% (11/124) and 9.7% (4/41), respectively. The mean duration of dialysis was 2.9 ± 5 years. Only 4 group B patients showed a positive result on the noninvasive stress test, but they had no obstructive disease on coronary angiograms. The incidences of ischemic heart disease after transplantation of groups A and B were 4% (5/124) and 4.8% (2/41), respectively ( P = .88). There was no death due to cardiac events in either group. Conclusions In this study, simple echocardiography showed an ability similar to stress test to predict ischemic heart disease in asymptomatic renal transplant candidates with good functional capacity, relatively younger age, lower prevalence of diabetes, and shorter duration of dialysis.

Milk urea nitrogen (MUN) and Milk protein (MP) are being used as indicators of the protein-energy balance and for actual farm feeding practices. The purpose of this study was to investigate the MUN and MP concentrations of individual cows and bulk tank milk to evaluate the dietary protein-energy balance from lactating Holstein cows. Mean MUN and MP concentrations in the milk samples obtained from 132,636 cows of 4,856 herd during Jan. 1999 to Dec. 2001 were 16.2 5.2mg/dl and 3.30 0.35%, respectively. The highest values were found during summer and lowest valued during winter in MUN. But, the average contents of MP were the highest during winter and the lowest during summer. In order to evaluate protein-energy balance for feeding, we set the level of recommended MP range of 2.903.29% in early lactation considering a negative energy balance. The recommended level of MP in mid-lactation and late lactation were set as 3.103.49%, and 3.303.69%, respectively. Recommended MUN range of 1218 mg/dl was determined through the whole lactation period. Individual cows milk were analyzed by the 9 types based on this levels of MP and MUN in this study. Among the total cows investigated, 26.8%, 25.8%, and 22.2% have shown the recommended criteria of MP and MUN values, respectively. Also, of total herds surveyed, 11.6% had MUN values lower than 12.0 mg/dl and 32.9% had values higher than 18.0 mg/dl and 44.5% of total herd have not met with the recommended criteria of MP values in bulk tank milk. In case of MP, out of the total herd surveyed, 26.0% had MP values lower than 3.10% and 24.0% had values higher than 3.30% and 50.0% had MP values outside the recommended interval (3.13.3%). This study has indicates that many dairy farms are under improper feeding management practice of the dietary protein-energy balance.

Transplantation of microencapsulated islets is proposed as an ideal therapy for the treatment of type 1 diabetes mellitus without immunosuppression. This strategy is based on the principle that foreign cells are protected from the host immune system by an artificial membrane. The aim of this study was to establish an ideal condition of microencapsulation using an air-driven droplet generator and alginate in vitro. The optimal conditions for islet encapsulation were an alginate inflow rate of 10 mL/h, CO2 flow rate of 2.0 L/min in a concentration of 2% alginate. For 2.5% alginate, the alginate inflow rate of 20 mL/h, CO2 flow rate 3.0 L/min was ideal; alginate inflow rate of 40 mL/h, CO2 flow rate of 4.0 L/min showed good microcapsules at 3% alginate. Viability of encapsulated islets was greater than 90%. In terms of insulin secretion, encapsulated islets secreted insulin in response to glucose in static culture medium. However, there was no normal response to low or high glucose challenge with a stimulation index less than 2.0. Microencapsulation of pig islets was successfully performed with air-driven droplet generator and alginate in vitro. Further studies about biocompatibility and glucose control in vivo may provide a useful tool for treatment of patients with diabetes mellitus.

Any attempt to improve organ donation would be of benefit due to the growing shortage of cadaveric sources for transplantation. Objective We compared the graft survivals and possible predictive variables among renal transplant recipients with organs from living unrelated (LURD) versus cadaveric donors (CD). Method Among 104 consecutive renal transplants performed from July 1992 to February 2003, 41 were from LURD and 24 from CD. Immunosuppressive regimens were based on cyclosporine and steroids with mycophenolate mofetil added after 1998. Patient and graft survivals were estimated using the Kaplan-Meier method and compared using log-rank tests. The significance level of predictive variables was analyzed with the Cox proportional hazard model. The follow-up period was 2 to 127 months (median 46 months). Results Eight recipients lost their grafts (six from LURD and two from CD) due to four chronic rejections, one acute rejection, one recurrence of primary disease, and one death with a functioning graft. The graft survival rates at 1, 3, 5, and 7 years were 97.6%, 91.9%, 88.5%, and 82.2% for LURD transplants versus 95.5%, 90.9%, 90.9%, and 90.9% for CD transplants, respectively ( P > .05). Delayed graft function and donor age (>55 years old) were statistically significant predictors of graft survival among LURD transplants. Donor age (>55 years old) and multiple preoperative transfusion history were significant in CD transplants. Conclusion LURD transplant survival was similar to that of CD transplants in our series. LURDs are an excellent source of organs to expand the donor pool.

Background For the first time at Asan Medical Center (AMC) we performed more than 400 liver transplantations (LTs) per year in 2011, despite same number of living donor liver transplantations (LDLTs). Methods Our OLT program was started in 1992, but not activated well due to the scarcity of deceased donor organs. Since adult LDLTs using a left lobe and then a right lobe were successfully performed in 1997, we have developed several innovative techniques and approaches for adult LDLT, for example, modified right-lobe graft reconstructing middle hepatic branches in 1998, dual graft LDLT using 2 left lobes in 2000; new criteria for hepatocellular carcinoma (HCC); as well as ABO-incompatible LDLT, the first in the world. As a result, the number of LDLTs has increased rapidly but reached a plateau recently. Nationwide efforts to promote deceased donation increased the number of deceased donor liver transplantation (DDLT). Results We have performed 317 LDLTs per year in 2010 and 2011, respectively. The number of LTs reached 403 in 2011. This large number was possible due to a remarkable increase of DDLTs from 50 in 2010 to 86 in 2011. Seventy-nine patients (68.1%) among 116 patients (28.8%) required an urgent LT receiving a DDLT. LT for HCC or ABO-mismatch comprised 50.3% (n = 150) or 8.7% (n = 35), respectively. In-hospital mortality rate in 2011 was 4.7%. Conclusions The increased LTs number at AMC was aided by the nationwide campaign.

Background There has been reported that the association between nodal spread and tumor size was disrupted in triple-negative breast cancer (TNBC) and it showed characteristically early relapse. The TNM (tumor–node–metastasis) staging system might not be equally effective as a prognostic indicator for all subtypes. The aim of our study was to evaluate the usefulness of the staging according to subtypes. Patients and methods We conducted a retrospective analysis of invasive breast cancer patients who received curative surgery at Samsung Medical Center from 2000 to 2004. Relapse-free survivals (RFS) by stage were analyzed. Results Thousand eight hundred and seventy-nine patients who were available clinicopathologic data were included. These patients were divided into three subtypes: hormone receptor (HR)+, human epidermal growth factor receptor 2+, and triple negative groups. As the stage became more advanced, the slope of each stage of the RFS curves of patients with HR+ and HER2+ steadily increased. In contrast, RFS curves intermingled and showed overlap from stage 1 to 3A in TNBC patients. There was only wide separation of RFS curves between stage 1-3A and 3B-3C in TNBC. Conclusions The current TNM staging system might not be enough for encompassing the tumor biology and for predicting outcomes to make therapeutic decisions for all BCs, especially for TNBC patients.

Objective To assess the results of the excision, plication and internal drainage techniques for hydrocele repair. Patients and methods Between January 1990 and June 1998, 132 patients (mean age 54.36 years, range 16–83) underwent repair for idiopathic hydrocele using one of three techniques (excision, eversion/plication or internal drainage); the complication and recurrence rates of each technique were evaluated. Results The excisional technique resulted in the highest complication rate (81%) and the internal drainage technique the lowest (7%). Postoperative scrotal oedema occurred in 74% of patients after plication and this was the highest rate among the techniques (P

Background. Adult porcine islet xenotransplantation into humans is greatly diminished by the difficulty to isolate islets because of their fragility. The goal of this study was to improve the efficacy of islet yields using endogenous trypsin inhibitor and histidine-tryptophan-ketoglutarate (HTK) perfusate. Method. We compared two porcine islet isolation protocols: Eurocollins solution for in situ pancreas perfusion without use of an endogenous trypsin inhibitor versus HTK solution including endogenous trypsin inhibitor for pancreas perfusion. Results. Endogenous trypsin inhibitor and HTK strategies significantly improved total islet yield, recovery, and islet index after purification (P

Living donors have always been the basic resources of transplantation in our country, where cadaveric harvesting is still hampered for various reasons. Objective The aim of this study was to compare graft survival rates between living unrelated donor (LURD) and living related donor (LRD), to assess the potential risk factors for the graft survival, and to discuss the role of LURD. Method From October 1991 to February 2003, 77 living donor renal transplants were performed: 41 were LURD and 36 were LRD transplants. The analyzed variables were donor relationship, recipient age and sex, donor age and sex, HLA-DR mismatching, nonspecific blood transfusion history of donor, acute rejection episodes, repeated rejection episode (more than 3 times), delayed graft function, recurred primary disease, and immunosuppressive regimen. Graft survival rate was assessed with the Kaplan-Meier method and the significance of possible variables with the Cox proportional hazard model. Results Eleven recipients lost their grafts (6 from LURD and 5 from LRD), most of them are due to chronic rejection (n = 7). Overall 3-, 5- and 10-year graft survival in live donors were 92.8%, 86.6%, and 76.9%, respectively. Graft survival at 3, 5, and 10 years being 91.9%, 88.5%, and 74.7% for the LURD versus 94%, 84%, and 78.8% for LRD transplants (P > .05). Acute rejection episodes, especially more than 3 times (risk ratio [RR] = 11.1) and preoperative multiple transfusion history (RR = 4.2) were significant factors on graft survival in our series. Conclusion Acute rejection episodes markedly decreased the long-term graft survival in live donor renal transplants. The use of LURD transplants provides graft survival comparable with LRD transplants and proper management to acute rejection is essential for long-term graft survival.

The reduced incidence of cancer observed in schizophrenia patients may be related to differences in genetic background. It has been suggested that genetic predisposition towards schizophrenia is associated with reduced vulnerability to lung cancer, and p53 gene is one of the candidate genes. We tested the genetic association between schizophrenia and lung cancer by analyzing polymorphic sites in the p53 gene. Genotype and allele frequencies at two polymorphic sites in the p53 gene (BstUI and MspI restriction sites in exon 4 and intron 6, respectively) were studied in Korean schizophrenia (n=179) and lung cancer patients (n=104). Comparisons of the genotype and allele frequencies of the MspI polymorphism revealed significant differences between schizophrenia and lung cancer patients. The results suggest that the p53 polymorphism specifically found in schizophrenia patients may be associated with reduced vulnerability to lung cancer.

Summary Suppurative gastritis was demonstrated in BALB/c mice 3 days after intragastric inoculation with 10 9 organisms of Listeria monocytogenes strain ATCC19113 (serotype 3). Also tested were four other strains of mice (C3H, C57BL/6, FVB and ICR) and three other strains of L. monocytogenes (HPB 3 [serotype 4b], HPB 410 [serotype 1/2a] and HPB 503 [serotype 1/2b]). After inoculation with ATCC19113 the numbers of bacteria found in the stomach wall were greater in C57BL/6 and ICR mice than in C3H and FVB mice; moreover, the gastritis produced in BALB/c and C57BL/6 mice was more severe than that produced in the other mouse strains. The gastritis produced in BALB/c mice with L. monocytogenes HPB 3, HPB 410 and HPB 503 was much more severe than that produced by ATCC19113. The inflammatory response occurred in the lamina muscularis and mucosa of the fundus. Massive necrosis of the gastric epithelium was observed, and there was oedema in a large part of the mucosal layer of the fundus. In addition, the submucosal layer was apparently expanded due to oedema, and in the cardia, the mucosal layer had become thin and flattened. Immunohistochemically, a polyclonal antibody against Listeria spp. produced labelling in areas of the gastric mucosa in which there was an inflammatory response and gastric epithelial necrosis. q 2003 Published by Elsevier Ltd.

A cell-scaled microbead system was used to analyze the force-dependent kinetics of P-selectin adhesive bonds independent of micromechanical properties of the neutrophil's surface microvilli, an elastic structure on which P-selectin ligand glycoprotein-1 (PSGL-1) is localized. Microvillus extension has been hypothesized in contributing to the dynamic range of leukocyte rolling observed in vivo during inflammatory processes. To evaluate PSGL-1/P-selectin bond kinetics of microbeads and neutrophils, rolling and tethering on P-selectin-coated substrates were compared in a parallel-plate flow chamber. The dissociation rates for PSGL-1 microbeads on P-selectin were briefer than those of neutrophils for any wall shear stress, and increased more rapidly with increasing flow. The microvillus length necessary to reconcile dissociation constants of PSGL-1 microbeads and neutrophils on P-selectin was 0.21 microm at 0.4 dyn/cm2, and increased to 1.58 microm at 2 dyn/cm2. The apparent elastic spring constant of the microvillus ranged from 1340 to 152 pN/microm at 0.4 and 2.0 dyn/cm2 wall shear stress. Scanning electron micrographs of neutrophils rolling on P-selectin confirmed the existence of micrometer-scaled tethers. Fixation of neutrophils to abrogate microvillus elasticity resulted in rolling behavior similar to PSGL-1 microbeads. Our results suggest that microvillus extension during transient PSGL-1/P-selectin bonding may enhance the robustness of neutrophil rolling interactions.

We have conducted a multicenter collaborative retrospective analysis to evaluate clinical characteristics and to compare prognostic scoring systems of 149 Korean patients with myelodysplastic syndromes (MDS). The median age of the patients was 53 years (range 17-82 years) with high of the patients being younger than 40 years. Median survival was 22.6 months, and 25 patients (17%) progressed to acute myelogenous leukemia (AML) with a median interval of 6 months (range 1-45 months). Major independent variables assessed by multivariate analysis were FAB subtypes and bone marrow (BM) blast percentages for survival and BM blast percentages for AML transformation. To compare the various scoring systems in the prediction for survival and transformation to AML, FAB, Sanz and Bournemouth scoring systems were applied to all patients, while the international prognostic scoring system (IPSS), Lille and Toyama scoring systems were applied to 91 patients. The Sanz scoring system (P < 0.0001), FAB classification (P < 0.0001), IPSS (P < 0.001), and Toyama scoring system (P < 0.005) were highly predictive for survival showed greater discrimination than that of the other systems. For AML transformation, the IPSS (P < 0.0001), Toyama scoring system (P < 0.0001), FAB classification (P < 0.0001), and Lille scoring system (P < 0.005) successfully discriminated risk groups. Although the prognostic factors and the distribution of age were different from those in Western reports, the IPSS and Toyama scoring system were applicable for predicting survival and leukemic transformation in Korean patients with MDS.

Introduction: Combination chemotherapy of R-CHOP is the standard treatment for patients with diffuse large B-cell lymphoma (DLBL) even in elderly patients. Patients with DLBL who are elderly and have poor performance status (≥ ECOG PS 2) are difficult to treatwith a full course of R-CHOP therapy. Objectives:We have tried to treat these advanced and poor performance status of elderly DLBL patients with rituximab and dose attenuated chemotherapy without anthracycline. (R-daCVP) We retrospectively evaluated the efficacy and safety of the R-daCVP chemotherapy in these patients. Methods: From January 1, 2005 to December 31, 2011, newly diagnosed stage III-IV DLBL patients who were considered inappropriate to receive standard R-CHOP chemotherapy were enrolled in this study. The inclusion criteria of our study were as follows; diagnosis of DLBL that was confirmed by histological examination in patients aged ≥70 years and poor performance status (PS) (ECOG PS ≥2). Patients received rituximab 375 mg/m on day 1 of each cycle. Dose attenuated CVP consisted of cyclophosphamide 600 mg/m and vincristine 1 mg/ m (maximum 2 mg) that were given intravenously on day 1 and oral prednisolone 80 mg on days 1–5. The treatment was repeated every 3 weeks and it was continued for six or eight cycles, with withdrawal due to toxicity or disease progression. Chemotherapy dosemodification was done by assessment of toxicities according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Results: We finally analyzed 13 patients. The median age was 78 years (range, 71-82). The distribution of the ECOG performance status was as follows: five patients (38.5%) with a performance status of 2, 8 patients (61.5%) with a performance status of 3. Eight patients (61.5%) were stage IV. Only 3 patients showed complete responses. Severe and fatal toxicity was significantly higher among these patients treated with even this less aggressive therapy. Four patients died due to grade 4 hematologic toxicities (grade 4 thrombocytopenia and grade 4 febrile neutropenia). Conclusion: In our study, we could not demonstrate that nonanthracycline dose attenuated combination immunochemotherapy with rituximab may have good potential in elderly DLBL patients with a poor PS. Eldely patients tend to have lower haemoglobin, leukocyte and platelet levels and may suffer greater toxicity from myelosuppressive chemotherapy. Careful toxicity monitoring and controlling the dose intensity or density may be needed in these fragile patients. Further studies are clearly warranted to identify the optimal management strategies for fragile and elderly patients with advanced DLBL.