High Lactate Dehydrogenase Levels Research Articles

Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib.

Treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been shown to prolong survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). The present study performed a retrospective analysis to investigate the association between the plasma lactate dehydrogenase (LDH) levels and survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. The medical charts of patients with EGFR mutation-positive NSCLC who were receiving treatment with EGFR-TKIs at Toyama University Hospital between 2007 and 2014 were assessed. The data from 65 patients were included in the analysis. Patients with higher plasma LDH levels exhibited shorter progression-free survival (6.2 vs. 13.2 months; P<0.01) and overall survival (10.5 vs. 36.1 months; P<0.01) periods compared with patients with lower plasma LDH levels. A Cox proportional hazards model identified that the plasma LDH level was associated with the progression-free survival (P=0.05) and overall survival (P<0.01). An association was demonstrated between the pretreatment plasma LDH level and the survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. Close observation is required in EGFR mutation-positive NSCLC patients exhibiting high plasma LDH levels following the initiation of treatment with EGFR-TKIs.

THE RESULTS OF TREATMENT OF ACUTE MYELOID LEUKEMIA IN EVERYDAY CLINICAL PRACTICE

Aim: To assess efficacy of the “7 + 3” regimen in non-selective groups of patients with acute myeloid leukemia (AML). Materials and methods: We retrospectively assessed medical documentations (inand out-patient case histories) of 105 AML patients who were on treatment in MONIKI from January 2002 to December 2011, with evaluation of clinical and hematological characteristics of patients, remission rates depending on age, serum lactate dehydrogenase (LDH) levels and time from diagnosis to the start of treatment, as well as overall survival. Results: In total, the standard regimen “7 + 3” was effective in 58% of AML patients. Remission was achieved in 70.5% of 17 patients with normal LDH levels and in 50.9% of 53 patients with high LDH levels (р < 0,05). In the patients aged from 18 to 30 years, the remission rate was 81%, in those from 31 to 60 years, in 61%. In the elderly patients (from 60 years and older), remission was achieved in 29% of cases (р < 0.05 compared to each of two other age groups). Remission was associated with the time from diagnosis to the start of treatment, being 16.7% in those where this time period exceeded 10 days and 60.8% in those where this time was less than 10 days (р < 0.05). The median overall survival was 11 months in the total group, 15 months in the patients who achieved remission after 2 treatment cycles and 6 months in those who did not respond to treatment. Comparison of the 2 groups with different AML types did not reveal any difference in the treatment results: overall survival in М0–М2 was 11 months and in М4–М5 10 months. Conclusion: Treatment of AML patients with “7 + 3” regimen provides a good anti-tumor effect. Achievement of remission depends on patient age, time to the start of treatment and LDH levels. The results obtained in non-selective group of patients are comparable to those published on selected group of patients.

Prognostic Significance of Preoperative Serum Lactate Dehydrogenase in Upper Urinary Tract Urothelial Carcinoma

BackgroundUpper urinary tract urothelial carcinoma (UUTUC) is one of the uncommon malignancies lacking of prognostic indicators. Lactate dehydrogenase (LDH) has been demonstrated to correlate with clinical outcomes in human cancers. In this study, we aimed to evaluate the prognostic implication of the preoperative LDH in UUTUC. Patients and MethodsA cohort of 100 UUTUC samples along with the preoperative LDH value was recruited from January 1990 to June 2011. The cutoff value was set at 245 u/L for the upper value of normal limitation. Univariate and multivariate analyses were conducted to determine the association of LDH with overall survival (OS) and disease-free survival (DFS). ResultsKaplan-Meier analysis revealed that high level of LDH (> 245 u/L) was significantly associated with poor OS (P < .001) and DFS (P = .002). Multivariate Cox proportional analysis indicated LDH, controlled by vascular invasion, pathological stage, lymph node status, subsequent bladder tumor, tumor grade, tumor necrosis, architecture, and multifocality, was as an independent predictor of OS (hazard ratio, 3.181; 95% confidence interval, 1.223-8.276; P = .018) and DFS (hazard ratio, 3.041; 95% confidence interval, 1.247-7.417; P = .015). Stratified showed that elevated serum LDH was correlated with the worse OS in patients without lymph node metastasis (P = .002) and those at advanced pathological stage (P < .001). ConclusionThe preoperative LDH was an independent prognostic factor for patients with UUTUC and could be used as a risk factor to predict the tumor aggressiveness.

Comparison of the Anti-inflammatory Effects of Proanthocyanidin, Quercetin, and Damnacanthal on Benzo(a)pyrene Exposed A549 Alveolar Cell Line

Phytochemical compounds are emerging as a new group of anti-inflammatory, antioxidant, and anti-cancer agents that help minimize toxicity in patients with pulmonary diseases. The goal of this study was to investigate the potential curative effects of Quercetin (QC), Damnacanthal (DAM), and Proanthocyanidine (PA) on inflammatory mediators and oxidative stress parameters and to examine the viability of the A549 cell line treated with benzo(a)pyrene (BaP) in vitro. The A549 cell line was treated with BaP, a BaP/QC combination, a BaP/DAM combination, and BaP/PA combination. Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and antiapoptotic proteins, and cell viability were assessed, and the results were compared. There were higher levels of lactate dehydrogenase after BaP treatment of A549 cell lines. Interferon-γ level significantly decreased in the QC, DAM, and PA-treated group (P < 0.001). IL-1β and TNF-α levels significantly decreased after PA and QC treatments (P < 0.001). Some of the oxidative stress markers (NO, MDA, TOS) and OSI decreased, while antioxidant (GSH) levels increased after treatment with QC, DAM, and PA. The QC and DAM treatments profoundly upregulated apoptotic gene expression and downregulated antiapoptotic gene expression. Viability of QC, DAM, and PA-treated cells was found to be significantly higher in comparison to the control and BaP-treated groups (p < 0.001). Our results revealed that A549 cell lines treated with BaP-stimulated necrosis produced higher level of inflammatory cytokines and oxidative stress parameters. Treatments with PA, QC, and DAM reduced inflammatory response induced by BaP exposure.

Bone marrow necrosis: literature review

Introduction: Bone marrow (BMN) is a rare pathologic entity that is commonly undiagnosed, and often associated with hematologic diseases. Methodology: We conducted a literature review at PubMed using marrow necrosis as key words. Our search retrieved 25 articles written in English, and a further 65 case reports. Results and discussion: BMN pathophysiology is not well understood, but appears to be associated with vascular injuries that lead to oxygen and nutrient deprivation. Destructive tumor factor alpha (TNF-α) activity is also likely involved in the development of endothelial and bone marrow sinusoidal lesions. Diagnoses of BMN are commonly indicated by anemia, thrombocytopenia, high levels of lactic dehydrogenase and alkaline phosphatase, and the identification of leukoerythroblastic reactions. Bone marrow (BM) aspirate and biopsy, and magnetic nuclear resonance imaging are the main diagnostic options. The only available treatments are those directed against the primary cause, with associated supportive care for what is ordinarily a rapidly lethal state. Conclusion: The search for an underlying associated malignancy is important for the management of BMN.

Prognostic Significance of Serum Lactate Dehydrogenase in Saudi Patients with Mycosis Fungoides: A Retrospective Study of 47 Patients

Background: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma and its advanced-stage (MF; stage IIB to IV)) has aggressive behavior. Lactate dehydrogenase (LDH) has been demonstrated to correlate with progression of malignancy specially lymphoma and leukemia. The LDH level is expected to be useful clinical tool for evaluating the progression of MF. Objective: This study aimed to evaluate the pretreatment LDH as a prognostic factor in Saudi patients with Mycosis fungoides. Methods: We designed a retrospective study using biopsy-based data collected from 1997 to 2015 at King Khalid University Hospital. The correlation of LDH levels with clinical stages of Mycosis fungoides was studied. Results: Of the 47 MF patients, there were 25 male and 22 female patients for a male: female ratio of 1.4:1. The mean patient age was 39 years; 87.2% (n=31) had limited stage of MF and 12.8 (n=6) had an advanced stage >IIA. There were 13 patients with a raised LDH at the time of diagnosis. All stage IA patients had normal LDH levels while stage IB, IIA and advanced stage had 20%, 50% and 100% elevated LDH, respectively. Conclusions: Our results suggest that high LDH level may be used as an independent prognostic factor to measure the progression of Mycosis fungoides.

Antioxidant activity, anti-proliferative activity, and amino acid profiles of ethanolic extracts of edible mushrooms.

Biological activities of various mushrooms have recently been discovered, particularly, immunomodulatory and antitumor activities. Herein, three edible mushrooms, Auricularia auricula-judae (AA), Pleurotus abalonus (PA) and Pleurotus sajor-caju (PS) extracted using Soxhlet ethanol extraction were evaluated for their antioxidative, anti-proliferative effects on leukemia cells. Using the Folin-Ciocalteau method and Trolox equivalent antioxidant capacity assay, phenolics and antioxidant activity were found in all sample mushrooms. Additionally, anti-proliferative activity of mushroom extracts against U937 leukemia cells was determined using a viability assay based on mitochondrial activity. PA (0.5 mg/mL) and AA (0.25-0.5 mg/mL) significantly reduced cell viability. Interestingly, PS caused a hormetic-like biphasic dose-response. Low doses (0-0.25 mg/L) of PS promoted cell proliferation up to 140% relative to control, whereas higher doses (0.50 mg/mL) inhibited cell proliferation. Against U937 cells, AA IC50 was 0.28 ± 0.04 mg/mL, which was lower than PS or PA IC50 (0.45 ± 0.01 and 0.49 ± 0.001 mg/mL, respectively). Furthermore, lactate dehydrogenase (LDH) leakage conferred cytotoxicity. PS and PA were not toxic to U937 cells at any tested concentration; AA (0.50 mg/mL) showed high LDH levels and caused 50% cytotoxicity. Additionally, UPLC-HRMS data indicated several phytochemicals known to support functional activities as either antioxidant or anti-proliferative. Glutamic acid was uniquely found in ethanolic extracts of AA, and was considered an anti-cancer amino acid with potent anti-proliferative effects on U937 cells. Collectively, all mushroom extracts exhibited antioxidant effects, but their anti-proliferative effects were dose-dependent. Nevertheless, the AA extract, with highest potency, is a promising candidate for future applications.

Clinical significance of interleukin-4 and interleukin-18 levels in aggressive non-Hodgkin's lymphoma patients.

Strong evidence indicates that tumor growth can be actively controlled by the immune system, and interleukins (ILs) are known to play an influential role in immune response regulation. Moreover, inflammatory cytokines are significantly involved in lymphoma pathogenesis. We aimed to investigate serum levels of IL-4 and IL-18 in aggressive non-Hodgkin's lymphoma (A-NHL) patients and their relationship with prognostic parameters and therapy outcome. These serum factors were measured by enzyme-linked immunosorbent assay in 46 patients with pathologically verified A-NHL before and after chemotherapy, and in 20 healthy controls. No significant difference in serum IL-4 (P = 0.11) and IL-18 (P = 0.261) levels was observed between the A-NHL and controls groups. None of the prognostic parameters analyzed significantly correlated with serum IL-4 concentration, while only lactate dehydrogenase (LDH) measurements were associated with IL-18 values. Serum IL-18 was elevated in the patients with high LDH levels compared to those exhibiting normal values (P = 0.045). In addition, no correlation was found between the concentrations of serum IL-4 and IL-18 in A-NHL patients (r = 0.188, P = 0.187). While IL-18 values did not change, serum IL-4 levels decreased following chemotherapy, independently from treatment response (P = 0.002). Our study is the first to report the response of serum IL-4 levels to chemotherapy. In conclusion, although IL-4 serum concentration has no diagnostic role, it is sensitivite to standard chemotherapy in A-NHL. However, serum IL-18 measurements have no diagnostic or prognostic role in this disease.

Elevated absolute monocyte count predicts unfavorable outcomes in patients with angioimmunoblastic T-cell lymphoma

This study was aimed at investigating the prognostic significance of the absolute monocyte count (AMC) in peripheral blood in patients with newly diagnosed angioimmunoblastic T cell lymphoma (AITL). AMC was performed in 73 therapy-naive patients with AITL in 2 institutions during 2008–2015, and higher AMC was observed in those with extranodal sites >1, bone marrow involvement, high lactate dehydrogenase level, the EBV infection, no response to treatment and high IPI, PIT, PIAI score group. The best AMC cut-off level at diagnosis was 0.8×109/L and the 3-year overall survival (OS) was 64% for patients with low AMC group (≤0.8×109/L) compared to 10% in high AMC group (>0.8×109/L) (P<0.001). Multivariate analysis showed that elevated AMC remained an adverse prognostic parameter. Our results suggest that AMC is an independent prognostic parameter for OS in patients with AITL, and AMC >0.8×109/L can routinely be used to identify high-risk patients with unfavorable survival.

Evaluation of the Revised International Staging System (R-ISS) in an Independent Cohort of Unselected Patients with Multiple Myeloma

The International Staging System (ISS), which is based on beta2-microblobulin (β2M) and serum albumin, has been widely used for the risk stratification of multiple myeloma (MM) patients, since 2003. Chromosomal abnormalities (CA) detected by iFISH have been also recognized as strong prognostic factors, while elevated serum lactate dehydrogenase (LDH) has been consistently associated with poor prognosis. In order to improve the prognostic power of ISS, IMWG has revised ISS (R-ISS) by adding high risk cytogenetics by iFISH and serum LDH: R-ISS-1 includes patients with ISS-1 (serum β2M level <3.5 mg/L and serum albumin level ≥3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)] and normal LDH levels (below the upper limit of normal (UNL)); R-ISS-3 includes patients with ISS-3 (serum β2M level >5.5 mg/L) and either high-risk CA or high LDH level; and R-ISS-2 includes all the other possible combinations. R-ISS was based on the data of 3,060 patients who had participated in clinical trials. However, it has not been validated in an independent cohort of unselected patients. Our aim was to evaluate R-ISS in consecutive, unselected patients, treated in a single center.Our study included 475 patients with available data for cytogenetics [t(4;14) and del17p by iFISH], LDH and ISS. Median age was 67 years (range 27-91); 53% were >65 years and 25% >75 years of age. Only 8.6% did not receive new drugs as primary therapy; 42% received IMiDs (19% thalidomide-based, 23% lenalidomide-based) and 49% bortezomib-based primary therapy, while 36% received ASCT. In the IMWG cohort, 65% had received ASCT, 6% no new drugs, 44% proteasome inhibitors and 66% IMiDs. Per ISS, 24% were ISS-1, 34% ISS-2 and 42% ISS-3. High risk cytogenetics (either t(4;14) or del17p) were present in 23.5% and elevated LDH in 15%. In the IMWG cohort used for the formulation of R-ISS, 38% were ISS-1, 38% ISS-2 and 24% ISS-3; thus, our patients had more often ISS-3 and less often ISS-1 disease. High risk CAs and elevated LDH were not different compared to our cohort of patients (24% and 13%, respectively). The difference in ISS disposition between the two cohorts probably reflects the unselected nature of our population, which also included patients with severe renal impairment who often are excluded from clinical trials.Per R-ISS, 85 (18%) patients had R-ISS-1, 83 (17.5%) had R-ISS-3 and 306 (64.5%) had R-ISS-2. The disposition in the original cohort was 28% for R-ISS-1, 62% for R-ISS-2 and 10% for R-ISS-3. This difference was due to the higher proportion of patients with ISS-3 disease in our cohort. The R-ISS disposition in those ≤65 years, was 21%, 60% and 19% for R-ISS-1, -2 and -3; among patients 66-75 years it was 19%, 63% and 18%, and among those >75 years it was 11%, 74% and 15%, respectively (p=0.128). The median follow up was 40 months; 57% of patients progressed or died and 63% have remained alive. Median PFS was 27 months and estimated median OS was 63 months. Median PFS for R-ISS-1, -2 and -3 was 34, 28 and 17 months, respectively (p<0.001). According to R-ISS, the probability of 3-year OS was 83%, 69% and 45% and of 5-year OS 77%, 53% and 19% for R-ISS-1, -2 and -3, respectively (p<0.001). In patients treated with ASCT, the probability for 5-year OS per R-ISS stage was 93%, 77% and 32%, respectively (p<0.001), while for patients not treated with HDM it was 64%, 41% and 13% (p<0.001). The probability for 5-year OS for patients treated with bortezomib was 95%, 69% and 18% for R-ISS-1, -2 and -3 (p<0.001) and for those treated with IMiDs, it was 68%, 41% and 23%, respectively (p=0.002).We evaluated the performance of R-ISS in patients ≤65, 66-75 and >75 years. In patients ≤65 years, the probability for 5-year OS was 84%, 71% and 29%, for R-ISS-1, -2 and -3 (p<0.001); for patients 66-75 years, it was 73%, 43% and 18% (p=0.001), while in patients >75 years, the median OS was >5 years, 35 and 29 month, respectively (p=0.122). Thus, R-ISS identified a group of patients >75 with favorable prognosis, although there was no significant difference in the OS for R-ISS-2 vs -3, probably due to the impact of other comorbidities and performance status of the very elderly.In conclusion, our data in consecutive, unselected patients, with differences in the characteristics and treatment approaches compared to the original IMWG cohort, verified that R-ISS provides significant prognostic information and it allows the identification of three different patient groups with clearly different outcome. DisclosuresTerpos:Novartis: Honoraria; Celgene: Honoraria, Other: travel expenses; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:Novartis: Honoraria; Celgene: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Onyx: Honoraria; Janssen-Cilag: Honoraria; Amgen: Honoraria.

A Frailty Scale Predicts Outcomes of Patients with Newly Diagnosed Multiple Myeloma Who Are Ineligible for Transplant Treated with Continuous Lenalidomide Plus Low-Dose Dexamethasone on the First Trial

Background: Many patient (pt) and disease factors have been shown to impact prognosis in multiple myeloma (MM). A recently described frailty scale categorized pts with MM into 3 groups: fit, intermediate, and frail based on age, comorbidities, and physical and cognitive functioning (Palumbo, Blood, 2015). These groups were predictive of risk of death. The pivotal phase 3 FIRST trial examined the impact of continuous therapy with lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) on outcomes in transplant-ineligible pts with newly diagnosed MM (NDMM; Benboubker, N Engl J Med, 2014). In this study, Rd continuous resulted in progression-free survival (PFS) and overall survival (OS) benefits compared with melphalan-prednisone-thalidomide (MPT). This analysis examined outcomes in pts by severity of frailty score in the FIRST trial, the largest clinical trial of transplant-ineligible NDMM to date. Methods: Pts with NDMM who were ineligible for transplant were randomized to treatment with Rd continuous, Rd for 18 cycles (Rd18; 72 weeks), or MPT for 12 cycles (72 weeks). Pts were categorized into 3 severity groups using a score based on age, Charlson Comorbidity Index score, and the Activities of Daily Living (measures of self-care) and Instrumental Activities of Daily Living (measures of usual activities) scales from the EQ-5D questionnaire at baseline, as previously described (Palumbo, Blood, 2015). This analysis examined PFS and OS outcomes by severity group in the overall pt population and between the Rd continuous and MPT arms, which were the primary comparators in this study, using an updated data cutoff of March 3, 2014. Results: This analysis included 1517 of 1623 pts from the intent-to-treat population; 106 pts were excluded because they did not have the required baseline data from the EQ-5D. The majority of pts enrolled in the FIRST trial were frail (54%) compared with fit (17%) or intermediate (30%). Similar breakdowns were observed across treatment arms (Figure 1). Frail pts were older and had higher Eastern Cooperative Oncology Group performance status scores, higher International Staging System (ISS) stage, higher lactate dehydrogenase levels, and worse renal function than fit or intermediate pts. In the overall pt population, better fitness was associated with significantly improved OS compared with worse fitness: fit vs intermediate (hazard ratio [HR] = 0.66; P = .004), fit vs frail (HR = 0.42; P Discussion: Results validated the feasibility of using the frailty scale for predicting risk of death in pts with NDMM and further demonstrated an association with PFS outcomes. The majority of pts fell into the frail category, which was associated with the poorest outcomes, indicating a need to further improve outcomes for a large proportion of pts with MM. Rd continuous resulted in PFS and OS benefits compared with MPT regardless of severity of frailty level, with the greatest benefits observed in fit pts. Poor outcomes of frail pts are likely further impacted by a higher proportion of deaths due to causes independent of MM compared with fit and intermediate pts, such as pre-existing comorbidities. These data support the use of Rd continuous as a standard frontline treatment option, even for frail pts with NDMM who are older and may have comorbidities or physical or cognitive impairments. Disclosures Facon:Celgene: Membership on an entity9s Board of Directors or advisory committees; Jansen: Membership on an entity9s Board of Directors or advisory committees; Millenium: Membership on an entity9s Board of Directors or advisory committees; Onyx: Membership on an entity9s Board of Directors or advisory committees; BMS: Membership on an entity9s Board of Directors or advisory committees. Hulin:Celgene Corporation: Honoraria; Bristol Myers Squibb: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Dimopoulos:Janssen-Cilag: Honoraria; Genesis: Honoraria; Amgen: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Onyx: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Mohty:Celgene Corporation: Honoraria, Research Funding. Zamagni:Celgene Corporation: Honoraria, Speakers Bureau; Janssen Pharmaceuticals: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Renwick:Amgen: Other: Travel; Bayer: Speakers Bureau. Tempescul:Gilead: Other: Export Board Committee. Palumbo:Novartis, Sanofi Aventis: Honoraria; Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria. Sturniolo:Celgene Corporation: Employment. Ervin-Haynes:Celgene Corporation: Employment.

Clinical Characteristics and Prognosis of 34 Patients with Mantle Cell Lymphoma: A Retrospective Analysis

To study the clinical characteristics and prognostic factors of 34 patients with mantle cell lymphoma (MCL). Clinical records of 34 MCL patients admitted from October 2007 to February 2015 in our hospital were analyzed retrospectively, the influcence of clinical characteristics, therapeutic protocol and biological indicators on overall survival (OS) was investigated. The median age of the patients at diagnosis was 58.4 years, with a significant male predominance (3.25: 1), 58.8% of patients had bone marrow involvement, 29.4% had alimentary tract involement, and 79.4% were in Ann Arbor stage III-IV. The expected 3 and 5-year overall survival (OS) rates of all the 34 patients were 63.6% and 55.6% respectively. Rituximab in combination with chemotherapy was not significantly superior to chemotherapy alone in terms of OS in this study (68.4 months vs. 51.8 months, P = 0.979). In univariate analysis, absolute monocyte count (AMC) >0.375 × 10(9)/L and increased lactate dehydrogenase (LDH) level at diagnosis were associated with poor OS (P < 0.05). Most patients were diagnosed at advanced stage. Rituximab plus chemotherapy can prolong OS time, but no statistically significant difference is observed, which maybe due to the fewer patients in this retrospective study. The high level of AMC and LDH at diagnosis are poor prognostic factors.

High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma

There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). Our aim was to determine whether NLR measured before the first infusion was associated with OS. Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07-1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01-4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54-3·06). High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.

Retrospective Analysis of Prognostic Factors in 187 Cases of Transformed Mycosis Fungoides.

Large cell transformation (LCT) of mycosis fungoides (MF) is associated with an aggressive clinical course, poor overall survival (OS), and variable CD30 expression. We retrospectively analyzed 1900 MF/Sézary syndrome patients' clinical, histologic and immunophenotype and identified 187 patients seen between 1982 and 2012. Most advanced stage patients with LCT were male 86 of 155 (55.4%) and 69 were female (44.5%). Incidence of LCT (n = 187) was 9.8% (187/1900) in skin and/or nodes of the entire MF/SS database population (n = 1900). Advanced stage patients represented 83% of patients whose median OS was 4.1 years (95% confidence interval [CI], 3.5-5.4). Early stage patients represented 17% with OS of 8.0 years. Among 187 LCT patients, 136 patients (73%) were diagnosed with LCT at the time of initial diagnosis of MF. Their median OS was 3.6 years (95% CI, 3.3-5.3). Of the 51 patients who had LCT diagnosed after their initial diagnosis of MF, their median OS was 8.8 years (P = .0001; 95% CI, 1.6-4.1). The OS for all LCT patients was 4.8 years, for patients older than 60 years of age OS was 3.7 years (95% CI, 2.7-5.4) and was 6.2 years (95% CI, 4.5-9.8) for patients younger than 60 years of age (P = .0001). An increased lactate dehydrogenase level was associated with a decreased OS (P = .03; hazard ratio, 1.5; 95% CI, 1.0-2.2). Patients with CD30 expression in ≥ 10% of the lymphocytes in skin biopsies were 40% more likely to survive than patients with low expression. In summary, risk factors associated with disease progression were advanced age, LCT at the time of initial diagnosis of MF, high levels of lactate dehydrogenase, and CD30 expression < 10%.

Prediction of Central Nervous System Relapse of Diffuse Large B-Cell Lymphoma Using Pretherapeutic [18F]2-Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography/Computed Tomography.

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare complication, but has a poor prognosis with unknown pathophysiology. Recent trials of CNS prophylaxis have shown to be ineffective, despite patient's selection using several known clinical risk factors. In this study, the authors evaluated the value of pretreatment [18F]2-Fluoro-2-deoxyglucose positron emission tomography in predicting CNS relapse in DLBCL patients.The authors analyzed 180 pathologically confirmed DLBCL patients, retrospectively. Patients underwent [18F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography before first line rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Clinical characteristics were evaluated and total lesion glycolysis (TLG) with a threshold margin of 50% was calculated.Among age, sex, Ann Arbor stage, International Prognostic Index, revised International Prognostic Index, high serum lactate dehydrogenase level, presence of B symptoms, bulky disease (≥10 cm), extranodal lesion involvement, bone marrow involvement, high metabolic tumor volume ( >450 mL), and high TLG50 (>2000), the high TLG50 was the only significant prognostic factor for predicting CNS relapse in a multivariate analysis (P = 0.04). Kaplan–Meir survival analysis between high TLG50 (>2000) and low TLG50 (≤2000) groups revealed significantly different mean progression free survival (PFS) of 1317.2 ± 134.3 days and 1968.6 ± 18.3 days, respectively (P < 0.001).High TLG50 on [18F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography is the most significant predictor of CNS relapse in un-treated DLBCL patients.

Viral etiology, clinical and laboratory features of adult hemophagocytic lymphohistiocytosis.

Secondary hemophagocytic lymphohistiocytosis (SHLH) is a potentially fatal hyperinflammatory syndrome with a heterogeneous etiology and has nonspecific clinical and laboratory findings. The diagnosis and treatment of adult SHLH is challenging because the etiology of the disease is difficult to identify, and the majority of reported cases are pediatric patients. The aim of this study was to describe the etiology, clinical characteristics, and outcomes of adult SHLH. Fifty‐four adult patients who fulfilled the criteria of SHLH were enrolled in the study. Viral etiology, blood biomarkers, and clinical manifestations of SHLH were analyzed in these patients. Twenty‐four SHLH patients had viraemia, whereas 30 SHLH patients were secondary to other diseases. Epstein‐Barr virus (EBV) was the most common virus that associated SHLH among all viruses studied. Severe SHLH patients with EBV‐viraemia presented significantly high levels of ferritin, lactate dehydrogenase, aspartate transaminase (AST), and alanine transaminase (ALT). Positively relationships existed between EBV DNA titers and levels of AST and ALT (P < 0.05). The prognosis of SHLH patients with EBV viraemia was worse than that of non‐EBV SHLH and non‐viral SHLH. Our data reveal that EBV is the major pathogen in virus‐associated SHLH, and EBV load influence disease development in SHLH patients with EBV infection that prognosis is worse than other viruses associated SHLH. J. Med. Virol. 88:541–549, 2016. © 2015 Wiley Periodicals, Inc.

Follow-up Serum Lactic Dehydrogenase as a Predictor of Distant Metastasis and Survival for Patients With Nasopharyngeal Carcinoma

Follow-up Serum Lactic Dehydrogenase as a Predictor of Distant Metastasis and Survival for Patients With Nasopharyngeal Carcinoma

Serum lactate dehydrogenase and survival following cancer diagnosis.

Background:There is evidence that high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in several malignancies, but its link to cancer-specific survival is unclear.Methods:A total of 7895 individuals diagnosed with cancer between 1986 and 1999 were selected for this study. Multivariable Cox proportional hazards regression was used to assess overall and cancer-specific death by the z-score and clinical categories of serum LDH prospectively collected within 3 years before diagnosis. Site-specific analysis was performed for major cancers. Analysis was repeated by different lag times between LDH measurements and diagnosis.Results:At the end of follow-up, 5799 participants were deceased. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer-specific death in the multivariable model were 1.43 (1.31–1.56) and 1.46 (1.32–1.61), respectively, for high compared with low prediagnostic LDH. Site-specific analysis showed high LDH to correlate with an increased risk of death from prostate, pulmonary, colorectal, gastro-oesophageal, gynaecological and haematological cancers. Serum LDH assessed within intervals closer to diagnosis was more strongly associated with overall and cancer-specific death.Conclusions:Our findings demonstrated an inverse association of baseline serum LDH with cancer-specific survival, corroborating its role in cancer progression.

Establishment and Validation of Prognostic Nomograms for Endemic Nasopharyngeal Carcinoma.

This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC). The nomogram was based on a retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided. Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort. The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.

Low forced expiratory volume is associated with earlier death in sickle cell anemia

AbstractPulmonary complications result in mortality in adults with sickle cell anemia (SCA). We tested the hypothesis that abnormal pulmonary function was associated with earlier death. A prospective cohort of adults with SCA, followed in the Cooperative Study for Sickle Cell Disease, was constructed using the first pulmonary function test at >21 years of age. Spirometry measures: forced expiratory volume in 1 second (FEV1), forced vital capacity, and total lung capacity were categorized based on age, gender, height, and race. Pulmonary function patterns were categorized based on the American Thoracic Society guidelines using both spirometry and lung volumes. A cohort of 430 adults with SCA, mean age 32.6 ± 9.5 (range, 21.0-67.8) years at time of first pulmonary function test, and a median follow-up of 5.5 years, was evaluated. A total of 63 deaths occurred. At baseline, 47% had normal, 29% restrictive, 8% obstructive, 2% mixed, and 14% nonspecific lung function patterns. In the final multivariable model, lower FEV1 percent predicted was associated with increased hazard ratio of death (HR per % predicted 1.02; 95% confidence interval [CI] 1.00-1.04; P = .037), as was older age (HR 1.07; 95% CI 1.04-1.10; P < .001), male sex (HR 2.09; 95% CI 1.20-3.65; P = .010), higher lactate dehydrogenase levels (HR per mg/dL 1.002; 95% CI 1.00-1.003; P = .015), and higher acute chest syndrome incidence rate (HR per event/year 10.4; 95% CI 3.11-34.8; P < .001). Presence of obstructive (HR 1.18; 95% CI: 0.44-3.20; P = .740) and restrictive (HR 1.31; 95% CI: 0.64-2.32; P = .557) pulmonary function patterns were not associated with earlier death. Understanding the pathophysiology of a low FEV1 percent predicted in individuals with SCA is warranted, enabling early intervention for those at risk.