Fludarabine,High Dose Cytarabine and Granulocyte Colony-Stimulating Factor (FLAG) as Consolidation Chemotherapy in Older Patients with Acute Myeloid Leukemia: A Retrospective Cohort Study

The study aimed to investigate the effect of consolidation treatment with fludarabine, high-dose cytarabine and granulocyte colony-stimulating factor or FLAG in older AML patients. The study included 41 eligible patients above 54 years old, who received both induction and consolidation chemotherapy for AML from 2008 to 2013. The study cohort had a minimum 24 months follow-up period. Survival analysis was carried out to assess patients’ overall survival and disease free survival based on types of consolidation regimens. The consolidation treatment with FLAG exerted a protective effect to both overall survival and disease free survival in older patients. Patients who were consolidated with FLAG regimen had a significant longer overall survival (log-rank, p = 0.0025) and disease free survival (log-rank, p = 0.0026). The median overall survival was longer (18.70 months) with the use of FLAG when compared to non-FLAG group (8.09 months). The median disease free survival was also longer (13.84 months) with use of FLAG when compared to the non-FLAG group (4.44 months). Regression analysis with Cox model yielded hazard ratio of 0.245 (p = 0.0094) in overall survival and 0.217 (p = 0.0068) in disease free survival. The use of FLAG as consolidation treatment was associated with approximately 60–80% reduction in hazard rates. The result was adjusted for age, race and gender in regression analysis. Older AML patients had longer remission and survival when consolidated with FLAG regimen after the induction chemotherapy.     

The prognostic value of circulating myeloblasts in patients with myelodysplastic syndromes

The prognostic value of peripheral blasts (PB) is not well-studied in patients with myelodysplastic syndromes (MDS). We evaluated the impact of PB on overall survival (OS) and transformation to acute myeloid leukemia (AML) in a large cohort. The MDS database at the Moffitt Cancer Center was retrospectively reviewed to identify patients with ≥?1% PB (PB-MDS) and those without PB (BM-MDS). We also assessed the correlation between PB and gene mutations. One thousand seven hundred fifty-eight patients were identified, among whom 13% had PB near the time of diagnosis. PB-MDS patients were more likely to be younger with trilineage cytopenia, complex karyotype, higher-risk disease, transfusion dependence, and therapy-related MDS. The rate of AML transformation was 49 vs. 26% (p?<?0.005) and median OS was 16.5 vs. 45.8 months (p?<?0.005) in the PB-MDS and BM-MDS groups, respectively. In Cox regression analysis, the presence of PB was an independent prognostic covariate for OS, HR 1.57 (95% CI 1.2–2). Among 51 patients with an available gene panel, the rate of ≥?1 gene mutation in the PB-MDS group (n?=?4) was 100% compared to 81% in the BM-MDS group (n?=?47). The presence of PB in MDS is an adverse independent prognostic variable that refines prognostic discrimination.     

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.     

Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.     

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI <?96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥?96.8 (5-year OS, 61.2 vs. 84.4%, P?<?0.001; 5-year PFS, 53.7 vs. 75.8%, P?<?0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI <?96.8 than in those with a GNRI ≥?96.8 (high-intermediate risk, 59.5 vs. 75.2%, P?=?0.006; high risk, 37.4 vs. 64.9%, P?=?0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.     

Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7–73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3–60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2–46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate >?75% were associated with increased OS (p?=?0.006 and p?=?0.003, respectively) and PFS (p?=?0.003 and p?=?0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥?8, were associated with decreased OS and PFS (p?=?0.02 and p?=?0.04, respectively). A high MSKCC score was associated with decreased OS (p?=?0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p?=?0.02 and p?=?0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.     

Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis

We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) and AA?+?AG vs. GG (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR?=?1.383, 95 % CI 1.142–1.676, P?=?0.022) and AA vs. AG?+?GG (OR?=?1.575, 95 % CI 1.361–1.823, P?<?0.001) in European patients with Crohn’s disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG?+?GG (OR?=?0.713, 95 % CI 0.545–0.933, P?=?0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD.     

The Synonymous Isocitrate Dehydrogenase 1 315C&gt;T SNP Confers an Adverse Prognosis in Egyptian Adult Patients with NPM1-/CEBPA-Negative Acute Myeloid Leukemia

Although the clinical features of isocitrate dehydrogenase (IDH) genetic aberrations have been well-characterized in acute myeloid leukemia (AML), definitive information on their prognostic significance is lacking. We aimed to explore the prognostic significance of IDH gene alterations in an Egyptian cohort of adult patients with de novo AML. Diagnostic peripheral blood samples from 51 AML patients were analyzed for the presence of mutations/SNPs in exon 4 of IDH1 and IDH2 genes using polymerase chain reaction amplification followed by direct sequencing. IDH mutational status had no impact on event-free survival (EFS) and overall survival (OS), whereas the presence of IDH1 315C>T SNP was significantly associated with inferior EFS (P = 0.037) and OS (P = 0.034) as compared with wild-type IDH1. IDH1 315C>T SNP but not IDH mutations is associated with unfavorable outcomes, suggesting that AML patients with IDH1 315C>T SNP can represent a new subgroup of patients which allows refined risk stratification.     

Correlation of sociodemographic and clinical parameters with depression and distress in patients with hematologic malignancies

A quarter of cancer patients struggle with distress or depression during their illness. Multiple organizations including the National Comprehensive Cancer Network recommend universal screening for distress and depression. Herein, we describe a universal screening program in patients with hematologic malignancies and factors associated with distress and depression. Between December 2013 and February 2015, patients with hematologic malignancies took the Patient Health Questionnaire 9 (PHQ-9) and Distress Thermometer (DT) prior to receiving their first outpatient parenteral chemotherapy. Patient demographic information as well as information regarding visit burden and baseline use of psychiatric medications were recorded. A PHQ-9 score of ≥?9 and a DT score ≥?4 suggested a high risk of major depression and distress. Intergroup comparisons of categorical and continuous variables were performed via chi-square and Wilcoxon rank-sum tests. Multivariate models were constructed using the stepwise selection technique using all potential variables. Two hundred forty-six patients with a median age at diagnosis 65 years (range 18–94 years) were included. In the multivariate analysis, a PHQ-9 score ≥?9 was associated with living alone (P?=?0.007), positive PHQ-2 (P?=?0.003), and high Charlson comorbidity index (CCI; P?=?0.02), while a DT score ≥?4 was associated with being married (P?=?0.03) and female (P?=?0.03). There was no other association with high scores on either questionnaire. Patients with hematologic malignancies often have prolonged treatment and surveillance. We identified subpopulations within this group who may be at high risk of developing distress and depression and who should be aggressively screened even when universal screening programs are not available.     

Impact of hematopoietic stem cell transplantation in patients with relapsed or refractory mantle cell lymphoma

Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n?=?111) or allogeneic (n?=?51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P?=?0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were >?60 years of age at HCT (P?=?0.017), higher score of HCT-specific comorbidity index at HCT (P?=?0.033), and receiving MCEC (ranimustine?+?carboplatin?+?etoposide?+?cyclophosphamide) regimen (P?=?0.017), while higher performance status at HCT (P?=?0.011) and longer interval from diagnosis to HCT (P?=?0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT.     

Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials

Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I² statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR?=?0.57, 95 % CI?=?0.54–0.61, p-value <0.00001], biochemical response [58.37 % vs. 21.87 %, RR?=?0.52, 95 % CI?=?0.48–0.56, p-value <0.00001], histological response [58.99 % vs. 27.13 %, RR?=?0.56, 95 % CI?=?0.50–0.63, p-value <0.0001], seroconversion of HBeAg [10.66 % vs. 5.56 %, RR?=?0.94, 95 % CI?=?0.91–0.97, p-value?=?0.0005], and HBeAg loss [14.59 % vs. 9.64 %, RR?=?0.92, 95 % CI?=?0.88–0.96, p-value?=?0.0002]. The safety analysis were carried out for adverse events such as headache [17.22 % vs. 17.34 %, OR?=?1.09, 95 % CI?=?0.81–1.46, p-value?=?0.58], abdominal pain [16.46 % vs. 14.34 %, OR?=?1.24, 95 % CI?=?0.90–1.72, p-value?=?0.19], and pharyngitis [22.22 % vs. 18.23 %, OR?=?1.12, 95 % CI?=?0.86–1.45, p-value?=?0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects.     

Comorbidities,repeated hospitalizations,and age ≥ 80 years as indicators of anemia development in the older population

Anemia represents a common condition among the elderly; however, its prevalence and causes are not well known. This retrospective analysis was performed on 981 patients aged ≥?60 in Poland over 2013–2014. The prevalence of anemia was 17.2% and increased with age. The predominant causes of anemia were the following: anemia of chronic disease (33.1%), unexplained anemia (28.4%), deficiency anemia (22.5%, including iron deficiency 13%), and chemo-/radiotherapy-induced anemia (8.9%). In the multivariate logistic regression model, factors increasing the risk of anemia were the following: age?≥?80 years (OR 2.29; 95%CI 1.19–4.42; P?=?0.013), the number of comorbidities (two diseases OR 2.85; 95%CI 1.12–7.30; P?=?0.029, three diseases OR 6.28; 95%CI 2.22–17.76; P?=?0.001, four diseases OR 4.64; 95%CI 1.27–17.01; P?=?0.021), and hospitalizations (OR 1.34; 95%CI 1.13–1.58; P?=?0.001). After a 2-year follow-up, the cumulative survival among patients without anemia in relation to the group with anemia was 90.76 vs. 78.08% (P?<?0.001). In the multivariate model, anemia (HR 3.33, 95%CI 1.43–7.74, P?=?0.005), heart failure (HR 2.94, 95%CI 1.33–6.50, P?=?0.008), and cancer (HR 3.31, 95%CI 1.47–7.49, P?<?0.004) were all significantly correlated with mortality. In patients ≥?60 years, the incidence of anemia increases with age, number of comorbidities, and frequency of hospitalizations and has an adverse impact on survival.     

The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies

Numbers of observational studies suggest that the JAK2 46/1 (GGCC) haplotype may increase the risk of myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT), but the results remain controversial. We aimed to examine the association between the JAK2 46/1 haplotype and risk of MPNs and SVT by conducting a meta-analysis. PubMed, EMBASE, Cochrane Library, CBM, and CNKI databases were searched to identify eligible studies without restrictions and by reviewing reference lists of obtained articles. Both fixed and random-effects models were used to calculate the summary risk estimates. We identified 26 observational studies of the JAK2 46/1 haplotype and risk of MPNs and SVT involving 8,561 cases and 7,434 participants. In the overall analysis, it was found that the JAK2 46/1 haplotype significantly elevated the risk of MPNs (rs10974944: C vs T: odds ratio (OR)?=?2.19, 95 % confidence interval (CI)?=?1.86–2.57, P?<?0.0001; CC vs TT: OR?=?4.63, 95 % CI?=?3.32–6.47, P?<?0.0001; CT vs TT: OR?=?2.49, 95 % CI?=?2.11–2.95, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.92, 95 % CI?=?2.51–3.39, P?<?0.0001; rs12343867: C vs T: OR?=?1.88, 95 % CI?=?1.59–2.22, P?<?0.0001; CC vs TT: OR?=?3.16, 95 %CI?=?2.14–4.65, P?<?0.0001; CT vs TT: OR?=?2.04, 95 % CI?=?1.51–2.74, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.25, 95 % CI?=?1.73–2.95, P?<?0.0001) and SVT (C vs T: OR?=?1.27, 95 % CI?=?1.06–1.52, P?=?0.011; CC vs TT: OR?=?2.33, 95 % CI?=?1.42–3.81, P?=?0.001; (CC?+?CT) vs TT: OR?=?1.25, 95 % CI?=?1.02–1.53, P?=?0.034). There was no evidence of a significant association between the rs12343867 and the risk of SVT in the genetic model (CT vs TT: OR?=?1.01, 95 % CI?=?0.80–1.29, P?=?0.906). This meta-analysis provides new evidence supporting the conclusion that the JAK2 46/1 haplotype enrichment is significantly associated with the development of MPNs and SVT in these patients.     

Clinico-biological characteristics and outcome of hepatitis C virus-positive patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Diffuse large B cell lymphoma (DLBCL) patients carrying hepatitis C virus (HCV) have higher risk of treatment toxicity and complications. The aim of this study was to assess the impact of HCV in a series of DLBCL patients treated with immunochemotherapy. 321 patients (161 M/160F; median age, 66 years) diagnosed with de novo DLBCL in a single center between 2002 and 2013 were included. Immunodeficiency-related lymphomas were excluded. HCV+ cases were defined by the presence of IgG anti-HCV. Main clinico-biological characteristics and outcome were analyzed according to the viral status. Two hundred ninety patients were HCV? and 31 HCV+. HCV+ patients were older (median age 71 vs. 64 years, P = 0.03), had more often B symptoms (P = 0.013), spleen (P = 0.003), and liver (P = 0.011) involvement, higher rate of early death (<4 months, P = .001), and shorter overall survival (OS). Eleven HCV+ patients had cirrhosis criteria. HCV+ patients with impaired liver function before or during treatment showed inferior OS. Elevated pre-treatment bilirubin correlated also with higher liver toxicity. In a multivariate analysis that included R-IPI score, serum beta2-microglobulin (β2m), HCV status, and presence of cirrhosis, only R-IPI, β2m, and cirrhosis showed independent prognostic impact on OS. The presence of HCV in DLBCL patients entails higher number of complications and early deaths; however, liver impairment and not the hepatitis viral status was the key feature in the outcome of the patients.     

Survival analysis of patients with Hodgkin lymphoma who failed high dose chemotherapy and autologous stem cell transplant

Hodgkin lymphoma (HL) patients failing after high dose chemotherapy (HDC) and auto-SCT have a poor outcome. Some patients may still benefit from further treatments. From 1996 to 2016, 137 HL patients (39.5%) out of 347 transplanted experienced post auto-SCT failure. Males/female 61%:39%, median age at auto-SCT 23.4 years and median follow-up 55.6 months (9–153). Type of failure was progressive (46%), relapsed (35%) or persistent disease/refractory disease (19%). Median overall survival (OS) from the time of failure is 20 months; 35 patients (25.5%) are alive. One hundred and four patients received treatment; the response rate was 45%; complete remission in 41 (30%) and partial remission in 21 (15%) patients. 1st interventions post auto-SCT were chemotherapy (39%), radiation therapy (35%) or best supportive care (24%). Twenty-seven patients with 2nd-SCT (allogeneic (15), auto-SCT (2)) and/or brentuximab (18 patients) had superior OS (50.6 months) vs other treatments (22.5 months, P value 0.037). COX regression multivariate analysis identified post auto-SCT treatment failure before 12 months (hazard ratio (HR) 3.37, CI 1.7–6.6, P value <?0.001), presence of B symptoms (HR 2.55, CI 1.4–4.6, P value 0.002), stages III–IV (HR 2.7, CI 1.5–4.9, P value 0.001), albumin <?4 g/dl (HR 1.76, CI 1.1–2.9, P value 0.027) and tumor >?5 cm (HR 1.1.9, CI 1.13–3.25, P value 0.015) as significant risk factors; P value <?0.001. KM OS with 0–1 factor (148.6 months): 2 factors (23.6 months) and 3–5 factors (9.4 months) (P value <?0.001). OS was 63%:25%:7% respectively with 0–1:2:3–5 factors respectively (P value <?0.001). Despite high-risk factors, 2nd-SCT/brentuximab use post HDC auto-SCT failure may result in durable survival.     

Retrospective Study of Pegaspargase,Gemicitabine, Oxaliplatin and Dexamethasone (Peg-GemOD) as a First-Line Therapy for Advanced-Stage Extranodal NK/T Cell Lymphoma

This study was conducted to retrospectively investigate the efficacy and safety of pegaspargase, gemicitabine, oxaliplatin and dexamethasone (Peg-GemOD) combination chemotherapy as a first-line therapy for advanced-stage extranodal NK/T cell lymphoma (ENKTL). Eighteen patients with newly diagnosed stage III/IV ENKTL were subjected to 3–6 cycles of Peg-GemOD chemotherapy. After 3 cycles of therapy, the overall response rate was 67 % (12/18) with a complete response rate of 28 % (5/18) and a partial response rate of 39 % (7/18). The median overall survival (OS) and progression-free survival (PFS) time were 10 and 8.5 months respectively. For those responders, the median OS and PFS time were significantly better than those of non-responders (median OS, 15 vs. 10 months; P = 0.001 and median PFS, 15 vs. 7 months; P = 0.001). Furthermore, patients with low plasma EBV-DNA levels after induction chemotherapy had a remarkably longer OS and PFS time. The toxicity of Peg-GemOD regimen was acceptable.     

Assessment of risk factors and left ventricular function in patients with slow coronary flow

Slow coronary flow (SCF) is characterized by delayed distal vessel opacification in the absence of significant epicardial coronary disease. Life-threatening arrhythmias and sudden cardiac death can occur; however, the pathological mechanism and influence on left ventricular function remain undetermined. We aimed to assess the risk factors and left ventricular (LV) function in SCF and evaluate the relationships between thrombolysis in myocardial infarction frame count (TFC) and the number of involved coronary arteries with LV function in patients with SCF. We included 124 patients who underwent coronary angiography because of symptoms of angina; 71 patients with angiographically proven SCF and 53 cases with normal coronary flow pattern. SCF was diagnosed as TFC >27 in at least one coronary artery. Complete blood count and biochemical parameters were compared between the two groups. Conventional echocardiography and tissue Doppler imaging were used to assess LV systolic and diastolic function. Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery mean TFC (mTFC) (r = 0.514, P < 0.001) and the number of coronary arteries with SCF (r = 0.628, P < 0.001). Early diastolic mitral inflow velocity (E) (0.66 ± 0.15 vs. 0.74 ± 0.17, P = 0.008), ratio of early to late diastolic mitral inflow velocity (E/A) (0.95 ± 0.29 vs. 1.15 ± 0.35, P = 0.002), global myocardial peak early diastolic velocity (gVe) (4.41 ± 1.25 vs. 4.96 ± 1.45, P = 0.037), and ratio of global myocardial peak early to late diastolic velocity (gVe/gVa: 1.09 ± 0.45 vs. 1.36 ± 0.58, P = 0.006) were decreased in patients with SCF compared with controls. gVe (3 vs. 0 branches, 4.08 ± 1.14 vs. 4.97 ± 1.45, respectively, P = 0.008) deteriorated significantly in patients with SCF involving three coronary arteries. mTFC negatively correlated with E and E/A (r = ?0.22, P = 0.02; r = ?0.20, P = 0.04, respectively). The number of coronary arteries with SCF negatively correlated with E, E/A, gVe and gVe/gVa (r = ?0.23, P = 0.02; r = ?0.25, P = 0.009; r = ?0.25, P = 0.008; r = ?0.21, P = 0.03, respectively). Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery TFC and the number of affected coronary arteries. Left ventricular global and regional diastolic function was impaired in SCF patients. Furthermore, the number of coronary arteries involved rather than coronary artery TFC determined the severity of left ventricular dysfunction in patients with SCF.     

The incidence of biopsy-proven transformation in follicular lymphoma in the rituximab era. A retrospective analysis from the Czech Lymphoma Study Group (CLSG) database

The aim of this study is to assess the incidence, risk factors, and outcome of biopsy-proven transformation in follicular lymphoma (FL) patients in the rituximab era. Transformation was analyzed in 1233 patients with initially diagnosed FL grades 1–3A, identified between 2002 and 2012 in the prospectively maintained Czech Lymphoma Study Group database. Only patients with histologically proven transformation (HT) were included. HT occurred in 58 cases at a median of 3.0 years from the initial FL diagnosis; the HT rate was 4% at 5 years. Transformation occurred most frequently at the first relapse (84% patients). Median OS from the HT was 2.5 years (95% CI 0.4–4.6) and 6-year OS with HT was shorter compared to all FLs (60 vs. 83.9%; 95% CI). A bulky tumor (≥?10 cm), increased lactate dehydrogenase, age ≥?60 years, and International Prognostic Index (intermediate/high risk), but not Follicular Lymphoma International Prognostic Index, were associated with transformation (p?<?0.05). In the first line, 70% of patients received rituximab (including 36% rituximab maintenance), 57% CHOP-like regimens, and 2.6% of patients were treated with fludarabine-based therapy, whereas 11% of patients were watched only. The patients treated with R-CHOP in the first line (n?=?591) showed the transformation rate at 5 years of 4.23% (95% CI 2.52–5.93); subsequent rituximab maintenance (n?=?276) vs. observation (n?=?153) was associated with a lower transformation rate (p.033; HR 3.29; CI 1.10–9.82). The transformation rate seems to be lower than in previous series, which may be influenced by broad use of rituximab, but prognosis of HT developed during therapy continues to be poor.     

Pooled analysis of the reports of carfilzomib/ixazomib combinations for relapsed/refractory multiple myeloma

We sought to evaluate the activity and safety of carfilzomib-/ixazomib-containing combinations for patients with relapsed/refractory multiple myeloma (RRMM). We searched published reports including carfilzomib-/ixazomib-containing combinations for RRMM. Finally, we identified 11 prospective studies covering 2845 relapsed/refractory patients. Carfilzomib- and ixazomib-containing combinations respectively resulted in an impressive overall response rate (ORR 77 vs. 64%, P?=?0.14), very good partial response or better (≥ VGPR 48 vs. 21%, P?=?0.001), complete response or better (≥ CR 14 vs. 7%, P?=?0.23), and clinical benefit rate (CBR 84 vs. 59%, P?=?0.0002). Subgroup analysis showed that the carfilzomib (CFZ) +lenalidomide (LEN) + dexamethasone (DEX) triplet regimen resulted into similar response outcomes to those from CFZ + DEX doublet regimen in ORR (77 vs. 78%, P?=?0.91), ≥VGPR (50 vs. 53%, P?=?0.84), and ≥ CR (13 vs. 12%, P?=?0.96) analysis in these previously heavily pretreated population. And, there were no statistically significant differences between IXA + LEN + DEX triplet regimen and CFZ + LEN + DEX triplet regimen in ORR (85 vs. 78%, P?=?0.55), ≥ VGPR (37 vs. 53%, P?=?0.19), and ≥ CR (18 vs. 12%, P?=?0.70) analysis. There were favorable trend towards proteasome inhibitors (PIs) + IMiDs + DEX in comparison with PIs + alkylating agent + Dex in ORR (79 vs 49%, P?<?0.00001), ≥ VGPR analysis (36 vs. 16%, P?=?0.008), and ≥ CR (16 vs. 3%, P?<?0.00001). Compared with current standard chemotherapy, carfilzomib containing combinations clearly improved overall survival (HR, 0.79; P?=?0.01), progression free survival (HR, 0.61; P?=?0.0001). Carfilzomib-/ixazomib-containing combinations produced clinical benefit for patients with R/RMM. PIs + IMiDs + DEX triplet regimens could be good options for such relapsed/refractory patients.     

Associations between <Emphasis Type="Italic">ERAP1</Emphasis> polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis

The aim of this study was to determine whether 11 polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) confer susceptibility to ankylosing spondylitis (AS). The authors conducted meta-analyses on associations between ERAP1 polymorphisms and AS susceptibility by using fixed and random effects models. A total of 19 articles were included in this meta-analysis, which comprised a total of 19,902 AS patients and 39,750 controls. The meta-analysis revealed a significant association between AS and the minor alleles of the rs30187 polymorphism in all study subjects (OR?=?1.255, 95 % CI?=?1.147–1.373, P?=?8.0?×?10^?8). Stratification by ethnicity led to the identification of a significant association between this polymorphism and AS in European patients (OR?=?1.283, 95 % CI?=?1.237–1.331, P?<?1.0?×?10^?9). Meta-analyses of the results for the rs27044, rs10050860, rs2287987, rs17482078, and rs26653 polymorphisms showed the same pattern that was found for rs30187. Interestingly, the rs27037 polymorphism was significantly associated with AS susceptibility in both European and Asian patients. Meta-analysis showed a significant association between AS and the minor alleles of the rs27980 and rs27582 polymorphisms in the East Asian patients (OR?=?0.904, 95 % CI?=?0.818–0.999, P?=?0.047; OR?=?0.871, 95 % CI?=?0.772–0.982, P?=?0.024, respectively) (Table 2). However, these polymorphisms have not been studied in Europeans. This meta-analysis shows that the ERAP1 polymorphisms are associated with the development of AS in Europeans and East Asians.