Chitotriosidase, a marker of innate immunity, is elevated in patients with primary breast cancer.

BACKGROUND: Cancer progression has been associated with altered immune cell function and activation. Neopterin, which is secreted by interferon-γ stimulated macrophages, exhibits an association with multiple cancer types and metastatic disease. Chitotriosidase, which is secreted by chronically activated macrophages and granulocyte-macrophage colony-stimulating factor stimulated neutrophils has not been studied in the setting of cancer. OBJECTIVE: The goal of this discovery study was to screen chitotriosidase for diagnostic capacity in detecting cancer and compare its operating characteristics with those of neopterin. METHODS: Serum from subjects with breast (n= 66) or prostate (n= 70) cancer, and from 204 subjects free of malignant disease were studied. Chitotriosidase was measured by enzyme activity assay, while neopterin was measured by a competitive enzyme immunoassay. Statistical analyses included group comparisons by Mann Whitney U test, diagnostic capacity by receiver operating characteristics (ROC) curve analysis and biomarker associations with physiologic and clinical measures by Spearman correlation. RESULTS: Chitotriosidase activity was significantly higher in both cancer types compared with gender matched controls, though only in breast cancer was the diagnostic capacity significant (area under the ROC curve of 0.97 ± 0.01). In contrast, neopterin was significantly elevated in prostate cancer and exhibited discriminatory capacity (area under the ROC curve of 0.76 ± 0.05). Age, BMI, % body fat and metastasis were variables that correlated with neopterin, but not chitotriosidase levels. CONCLUSIONS: The operating characteristics of serum chitotriosidase were different from neopterin and further analysis of chitotriosidase as a biomarker for breast cancer is warranted.

Sickle cell disease in the older adult.

Sickle cell disease (SCD) is an inherited haemoglobin disorder, associated with recurrent painful episodes, ongoing haemolytic anaemia and progressive multi-organ damage. Until the early 1990s, survival beyond the fourth decade for a patient with SCD was considered unusual and prompted case reports. Nowadays, in countries with developed health care systems, more than 90 percent of newborns with SCD survive into adulthood. Nevertheless, their life expectancy is still shortened by more than two decades compared to the general population. With an increasing life expectancy, SCD has now evolved into a debilitating disorder with substantial morbidity resulting from ongoing sickle cell vasculopathy and multi-organ damage. Limited data on health care issues of older adults with SCD poses multiple challenges to patients, their families and health care providers. In this review, we will address and discuss acute and chronic complications of SCD with a special focus on the older adult.

Treatment of catheter-related deep vein thrombosis in patients with acute leukemia with anticoagulation.

Patients with acute leukemia develop venous thrombosis (VT) related to central venous catheters (CVCs). Anticoagulation (AC) in these patients who are thrombocytopenic and often coagulopathic is challenging. To evaluate the safety and efficacy of AC in treating CVC-related VT, we retrospectively compared outcomes of patients with acute leukemia who were treated or not with AC during induction chemotherapy and post-discharge. Twenty-one patients with CVC-related VT received AC, 14 did not. VT resolved in 80% of patients in the AC group (similarly with low-dose and high-dose enoxaparin) and 45% in the non-AC group (p = 0.11). Fourteen (67%) patients in the AC group are alive (median survival not reached), compared to four patients (29%) in the non-AC group (median survival 9 months) (p = 0.015) with a hazard ratio (HR) of 0.32 (95% confidence interval: 0.12-0.85) in favor of AC. HR remained < 1 after adjustments for leukemia type and cytogenetics. Bleeding (< grade 4) occurred in five and one patients in the AC vs. non-AC groups, respectively (p = 0.37).

Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades.

BACKGROUND: Acute myeloid leukemia (AML) is the common form of acute leukemia in adults, accounting for over 80% of all acute leukemias in individuals aged >18 years. Overall 5-year survival remains poor in older AML patients; it is <5% in patients aged >65 years. In this study, the authors examined whether survival has improved for subsets of geriatric AML patients over 3 successive decades. METHODS: Surveillance, Epidemiology and End Results (SEER) data were used to determine trends in relative survival by age among 19,000 patients with AML over 3 successive decades (1977-1986, 1987-1996, and 1997-2006). Relative survival rates (RRs) with 95% confidence intervals (CIs) were calculated as measures of survival. RESULTS: Overall, the RRs increased for each successive decade (1977-1986, 1987-1996, and 1997-2006) in patients ages 65 to 74 years, with improvements in 12-month survival from 20%, to 25%, to 30%, respectively. Findings were similar for 24-month, 36-month, 48-month, and 60-month survival. However, survival rates did not improve in patients aged ≥75 years. The oldest old patients (aged ≥85 years) had the lowest survival rates, with no apparent improvement. CONCLUSIONS: This analysis of a large data set demonstrated that, although overall survival remained unsatisfactory among older patients, it improved in the younger old (ages 65-74 years). Survival of older old AML patients has not been favorably impacted by available AML therapies or supportive care, and intervention in this age group is best undertaken on a clinical trial.

Diminished quality of life and physical function in community-dwelling elderly with anemia.

The occurrence of anemia in older adults has been associated with adverse outcomes including functional decline, disability, morbidity, and mortality. It is not clear to what extent these outcomes are the result of the anemia or concurrent illness. We performed a cross-sectional, observational study to determine whether lower hemoglobin concentrations in older adults are associated with reduced health-related quality of life, functional status, depression, disability, and physical strength, independent of chronic disease. Three sites participated in this research: an academic geriatric practice, a hospital-based geriatric outpatient unit, and a community-based multispecialty internal medicine group. Health-related quality of life and functional status were measured using the Short Form-36 Health Survey (SF-36) and the Functional Assessment of Chronic Illness Therapy-Anemia (FACIT-An). Disability and depression were assessed using the Instrumental Activities of Daily Living (IADL) and the Geriatric Depression Scale (GDS) questionnaires, respectively. Handgrip strength was used as a physical performance measure. Anemia was defined as hemoglobin <13 g/dL for men or <12 g/dL for women. The mean SF-36 physical health component summary scores were 38.9 (with anemia) and 44.1 (without anemia) (p<0.001). Anemia was associated with greater fatigue (p < 0.001), lower handgrip strength (p = 0.014), increased number of disabilities (p=0.005), and more depressive symptoms (p = 0.002). Multivariate regression analysis, adjusted for demographic and clinical characteristics, demonstrated strong associations for reduced hemoglobin, even within the "normal" range, and poorer health-related quality of life across multiple domains. Thus, anemia was independently associated with clinically significant impairments in multiple domains of health-related quality of life, especially in measures of functional limitation. Mildly low hemoglobin levels, even when above the World Health Organization (WHO) anemia threshold, were associated with significant declines in quality of life among the elderly.

A phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders.

Triapine is a potent ribonucleotide reductase (RR) inhibitor that depletes intracellular deoxyribonculeotide pools, especially dATP. We designed a Phase I trial of Triapine followed by the adenosine analog fludarabine in adults with refractory acute leukemias and aggressive myeloproliferative disorders (MPD). Two schedules were examined: (A) Triapine 105 mg/m(2)/day over 4 h followed by fludarabine daily x 5 (24 patients, fludarabine 15-30 mg/m(2)/dose); (B) Triapine 200 mg/m(2) over 24h followed by 5 days of fludarabine 30 mg/m(2)/day (9 patients). Complete and partial responses (CR, PR) occurred in Schedule A (5/24, 21%), with CR occurring at the 2 highest fludarabine doses (2/12, 17%). In contrast, no CR or PR occurred in Schedule B. Four of the 5 responses occurred in patients with underlying MPD (4/14, 29%). Drug-related toxicities included fever and metabolic acidosis. Triapine 105 mg/m(2) followed by fludarabine 30 mg/m2 daily x 5 is active in refractory myeloid malignancies and warrants continuing study for patients with aggressive MPD.