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Purpose: Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL. Materials and methods: This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. A CAR cutoff value of 0.794 was determined, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high (> 0.794) and low (≤ 0.794) CAR groups. Results: After induction therapy, complete response was achieved in 8 (32.0%) and 39 patients (76.5%) in the high and low CAR groups, respectively. During the median follow-up of 57.5 months, the high CAR group had significantly worse 5-year PFS and 5-year OS rates. Even with adjustment for the International Prognostic Index (≥ 3), Prognostic Index for PTCL-unspecified (≥ 3), and T cell score (≥ 2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04–7.86, p < 0.001) and OS (HR: 2.97, 95% CI: 1.33–6.64, p = 0.008). Conclusion: CAR may play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility. [ABSTRACT FROM AUTHOR]

Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM. [ABSTRACT FROM AUTHOR]

The C-reactive protein-to-albumin ratio (CAR) has not been assessed in diffuse large B cell lymphoma (DLBCL, the most common non-Hodgkin lymphoma). This retrospective study evaluated the prognostic value of CAR in 186 DLBCL patients. A CAR value of 0.158 was selected as the most discriminative cut-off for identifying patients with high CAR values (73/141 patients, 51.8%). During a median follow-up of 32.5 months, the high CAR group had significantly poorer complete response to induction therapy (64.4% vs. 92.6%; p < 0.001), 3-year overall survival (OS) (68.3% vs. 96.2%; p < 0.0001), and 3-year progression-free survival (PFS) (53.5% vs. 88.0%; p < 0.0001). After adjusting for the International Prognostic Index components, a high CAR value independently predicted poor OS (HR: 6.02, 95% CI 1.19–30.38; p = 0.030) and PFS (HR: 3.62, 95% CI 1.40–9.36; p = 0.008). In an independent validation cohort (n = 50), patients with CAR > 0.158 also showed worse 3-year OS (47.9% vs. 87.2%, p = 0.0035) and 3-year PFS (36.1% vs. 82.1%, p = 0.0011). A high CAR remained significantly associated with poor outcomes for > 60-year-old patients (OS: p = 0.0038, PFS: p = 0.0015) and younger patients (OS: p = 0.0041, PFS: p = 0.0044). Among older patients, a high CAR value also predicted non-relapse mortality (p = 0.035). Therefore, the CAR might complement the International Prognostic Index in DLBCL cases. [ABSTRACT FROM AUTHOR]

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) and pure red cell aplasia (PRCA) appear to be more prevalent in Asian countries including Korea. However, there are no exact data regarding its prevalence and frequency of allogeneic hematopoietic cell transplantation (HCT) in Korea. Here, we present demographic data relating to AA/PRCA/MDS in Korea. Data were prepared by retrieval from a computerized database maintained by the National Health Insurance Service and Korea National Statistical Office. HCT data were collected from all HCT centers in Korea. The crude incidence rate of AA decreased from 2002 to 2010 and from 35 to 28 per million persons. Females were more affected by AA. The peak ages of onset of AA were in the seventh decade or older. The frequency of HCT for AA increased from 2002 to 2012 and from 69 to 131 per year. The crude incidence rates of MDS increased from 2002 to 2010, with 8-20 per million persons, and the frequency of HCT also increased, from 30 in 2002 to 132 in 2011. Even allowing for the possibility of overestimation, the crude incidence of AA is significantly higher in Korea than in western countries. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the changes in health-related profiles including quality-of-life (HRQoL) in the chronic myeloid leukemia (CML) patients who discontinued imatinib (IM). An HRQoL survey composed of 43 parameters about IM-related adverse events (AEs), physical health-related and mental health-related was provided at baseline and 6 months post-discontinuation. A total of 55 patients with a sustained UMRD over 6 months were analyzed. Although the majority of IM-related AEs were significantly improved, unexpectedly pruritus and musculoskeletal pain worsen or newly develop in 29.1% and 21.8% of patients, respectively. The improvements in physical and mental health condition were variable in individual patients. In addition, rapid restorations of the hematological and biochemical parameters were observed. The results showed the changes of HRQoL and laboratory tests in treatment-off patients and the necessity of continuing physical and mental support for some patients in tyrosine kinase inhibitor (TKI)-off studies. [ABSTRACT FROM PUBLISHER]

Chang MH, Lee K, Lee K-Y, Kim YS, Kim YK, Kang J-H. Prognostic role of integrin β1, E-cadherin, and rac1 expression in small cell lung cancer. APMIS 2012; 120: 28-38. Integrin β1 mediates cellular adhesion to the extracellular matrix (ECM) and is correlated with highly invasive and metastatic behavior in small cell lung cancer (SCLC). E-cadherin (ECAD) is a calcium-dependent cell-cell adhesion receptor that restricts invasion of cells and reduces metastasis. Rac1 is involved in the regulation of the actin cytoskeleton, adhesion, migration, invasion, and tumor metastasis. The aim of this study was to examine integrin β1, ECAD and rac1 expression in SCLC and to analyze the prognostic value of these markers in patients with SCLC. We analyzed integrin β1, ECAD, and rac1 expression in 112 SCLC tissues by immunohistochemical staining. Correlative analyses between integrin β1, ECAD, and rac1 expression and cliniopathological factors were performed. A total of 65 patients had extensive disease (ED) (58%), and 47 had limited disease (LD) (42%). The median follow-up duration was 61 months (range: 14-117 months), and the median progression free survival (PFS) and overall survival (OS) were 6.1 months (range: 4.8-7.4 months) and 9.7 months (range: 8.1-11.3 months), respectively. The expression of integrin β1, ECAD, and rac1 protein was observed in 64, 73, and 99 of SCLC tissues, respectively. The correlative analyses between integrin β1, ECAD, or rac1 expression and various clinical parameters did not show any statistical significance. However, the ECAD expression was associated with OS in the entire cohort. In contrast, the expression of integrin β1 and rac1 was not associated with PFS or OS. In a subgroup analysis, patients with less than two metastasis had significantly longer OS (p = 0.047) if their tumors expressed integrin β1 compared to those without integrin β1 expression. In addition, OS was longer for patients with ECAD positive tumors compared to those whose tumors did not express ECAD in males (p = 0.032) and patients who never smoked (p < 0.001). Multivariate analysis showed that LD (p = 0.004), overall response rate (p = 0.003), and expression of ECAD (p = 0.015) were the independent good prognostic factors for OS. LD (p = 0.024), overall response rate (p < 0.001), and less than two metastasis (p = 0.003) were prognostic factors for longer PFS. These results suggest that ECAD expression may be useful as a prognostic indicator in patients with SCLC. [ABSTRACT FROM AUTHOR]

Introduction: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. Patients and Methods: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1-8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m2 over 3 h, and at a dose of 2 g/m2 per day; continuous infusion was administered on 6 consecutive days (2 g/m2/6 days) every 3 weeks. Results: After a median follow-up of 49 months (range 10-114), median PFS was 2.9 months (range 0.4-9.3) and median overall survival 8.7 months (range 0.4-57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7-7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3-4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. Conclusion: HDI at a total dose of 14 g/m2 with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A retrospective analysis to compare the treatment outcomes of two regimens with different doses of methotrexate (MTX). Seventy-two patients, newly diagnosed with primary central nervous system lymphoma between 1995 and 2006, were included. All patients were treated with one of the two different MTX regimens depending on when the diagnosis was made. Thirty-six patients diagnosed between 1995 and 2002 were treated with 1 g/m2 of intravenous MTX (HD-MTX 1 g/m2, cohort 1). The other 36 patients, diagnosed between 2003 and 2006, received 3.5 g/m2 of intravenous MTX (HD-MTX 3.5 g/m2, cohort 2). The median age was 47 years (range, 17-78 years) and 42 patients (58.3%) were male. The median overall survival (OS) and progression-free survival (PFS) of all patients was 90.3 and 52.9 months, respectively. Although OS and PFS was not statistically different between the two cohorts, cohort 2 achieved higher complete response/unconfirmed complete response rates than cohort 1 at an evaluation conducted between completion of intravenous MTX therapy and the initiation of radiotherapy (52.8% vs. 16.7%, respectively; p = 0.005). Furthermore, there were no deaths within 6 months of MTX therapy for the cohort 2, whereas there were eight deaths by 6-months for cohort 1 (p = 0.003). Even though cohort 2 failed to show superior survival outcomes compared with cohort 1 after sequential brain radiotherapy and intravenous cytarabine, the higher early CR/CRu rate of cohort 2 compared with cohort 1 might indicate that a high dose of MTX is desirable. [ABSTRACT FROM AUTHOR]

We performed a retrospective multicentre analysis to study the clinical features and treatment outcomes of B-lymphoblastic lymphoma (B-LBL) and T-lymphoblastic lymphoma (T-LBL) in Asian adult patients, and identify risk factors that predict relapse and poor prognosis. Fifty-five newly diagnosed patients (45 T-LBL and 10 B-LBL) were analysed. All patients were treated with intensive chemotherapy regimens including VPDL (vincristine, prednisolone, daunorubicin, L-asparaginase), CALGB (Cancer and leukemia group B), and Stanford/Northern California Oncology Group (NCOG). There was no difference of clinical features between B- and T-LBL except the frequent site of involvement. The overall response rate including complete response (28/55, 50.9%) and partial response (18/55, 32.7%) was 83.6%. Among 46 responders, 22 patients relapsed leading to 20 deaths. Partial responders showed more frequent relapse (10/18, 55.6%) than complete responders (11/28, 39.2%). The median progression-free survival (PFS) was 17 months (95% confidence interval, 11.5-22.5), and the 2-year overall survival was 52 ± 7% with a median follow-up of 50 months (range 8-152). Treatment outcome of T-LBL and B-LBL was not significantly different in terms of response and survival. The presence of pleural effusion was significantly prognostic for overall and PFS (p < 0.05). In conclusion, clinical features and treatment outcome of Asian adult LBL were comparable to previous results, and the prognosis is still poor despite intensive chemotherapy. [ABSTRACT FROM AUTHOR]

We designed this phase I/II study of docetaxel–oxaliplatin combination chemotherapy to determine the dose-limiting toxicity (DLT), maximum tolerated dose and efficacy as a first-line treatment in patients with advanced gastric cancer. Patients with histologically proven, chemo-naive gastric adenocarcinoma were eligible. For the phase I part, three dose levels of oxaliplatin and docetaxel every 3 weeks were tested in a cohort of three patients for each level (respectively, 100 and 60 mg/m2, 100 and 75 mg/m2, 130 and 75 mg/m2). Patients were treated up to a maximum of nine cycles of oxaliplatin and docetaxel unless there was documented disease progression, an unacceptable adverse event, or withdrawal of consent. No DLT was observed at any of the three levels tested in the phase I portion. Therefore, oxaliplatin 130 mg/m2 and docetaxel 75 mg/m2 were recommended for the phase II study. All 47 patients were evaluable for toxicity and treatment response. The overall response rate was 55.3% (95% CI, 40.6–70.1%) and median duration of response was 4.2 months (range 0.9–9.5 months). After a median follow-up duration of 13.3 months, median overall survival was 12.7 months (95% CI: 10.4–14.9). The median time to progression was 5.0 months (95% CI, 3.4–6.5 months). The main toxicities (grade 3 or 4) were febrile neutropenia (14.9%), neutropenia (23.4%), diarrhea (10.6%) and neurotoxicity (8.5%). The combination of docetaxel and oxaliplatin was feasible with favorable toxicity profile and showed a promising anti-tumor activity in unresectable, metastatic gastric cancer patients. [ABSTRACT FROM AUTHOR]

We investigated the value of Epstein-Barr virus (EBV) DNA load in unfractionated whole blood for the diagnosis and prognosis of EBV-associated lymphoma. From July 2004 to July 2007, we compared EBV DNA loads in 101 patients with lymphoma and 105 control individuals. The median copy number of EBV was higher in patients with EBV-positive lymphoma (p<0.001). In patients with natural killer (NK)/T-cell lymphomas, the median EBV DNA load at presentation was significantly related to the stage (p = 0.011) and response (p = 0.026). The newly proposed classification model for NK/T cell lymphoma showed EBV DNA load differed significantly between patients with upper and extra-upper aerodigestive tracts (p = 0.017). In 16 patients with NK/T-cell lymphoma monitored serially, EBV DNA load correlated well with the treatment response and clinical course. Further prospective studies are required to evaluate the diagnosing and monitoring role of whole blood EBV DNA for uniformly treated patients. [ABSTRACT FROM AUTHOR]