The relation between cigarette smoking and risk of acute myeloid leukemia: an updated meta-analysis of epidemiological studies.

Smoking has been postulated as an environmental risk factor for acute myeloid leukemia (AML). The primary objective of this meta-analysis of observational studies was to evaluate the epidemiologic relationship between smoking and the risk of development of AML. Twenty-three studies published between January 1993 and December 2013 were included in our analysis, and accounted for 7,746 cases of AML. The outcome of interest was the relative risk (RR) with 95% confidence interval (CI) of developing AML in adult cigarette smokers in comparison with non-smokers, and was estimated using the random-effects model. Our results showed that current and ever smokers have 40% (RR 1.40, 95% CI 1.22-1.60; P < 0.001) and 25% (RR 1.25, 95% CI 1.15-1.36; P < 0.001) increased risk of developing AML when compared with non-smokers. The increased RR of AML was increased regardless of sex, study design, geographical region, and quality of the studies. Intensity of smoking of <10, 10-20, 20-30, and >30 cigarettes per day was associated with RRs of AML of 1.27, 1.36, 1.55, and 1.77, respectively (P < 0.001 for trend). Duration of smoking of <20 and >20 years was associated with RRs of 1.07 and 1.44, respectively (P < 0.001 for trend). Cumulative smoking of <10, 10-20, 20-30, and >30 pack-years was associated with RRs of 1.13, 1.23, 1.39, and 1.71, respectively (P < 0.001 for trend). Overall, cigarette smoking proves to be a significant risk factor for the development of AML in adults.

The girl with the iron tattoo.

We describe a young woman with profound anemia whose serum iron studies were incongruous with what we expected from iron deficiency anemia. Her high serum iron was not fully explainable until we examined the patient and noticed a large black tattoo on her left flank area. Apparently iron oxide in the ink used for the tattoo was absorbed transcutaneously and led to high serum iron in the face of the other data, which suggested iron deficiency. She was slow in mobilizing her serum iron for erythropoiesis and we discovered that there was a concurrent acute B19 parvovirus infection, which impeded utilization of the iron for red blood cell production. We believe that this case report reinforces the imperative to always do a careful physical examination with any patient who has anemia, and also illustrates the potential toxicity of tattoo ink. The impairment of utilization of the serum iron because of the patient's acute B19 parvovirus infection demonstrates the many consequences of infection induced aplastic anemia.

Recognition and management of extended spectrum beta lactamase producing organisms (ESBL).

ESBL organisms provide a continuing challenge in the geriatric community. They are increasingly prevalent, and pose unique challenges in treatment. Carbapenems are the mainstay of therapy; however they are expensive medications that require prolonged intravenous administration. Carbapenem resistance is a growing concern among frequently hospitalized patients and nursing home residents, and options for treatment of MDROs are limited. Attempts at minimizing the spread of beta-lactamase producers through hygiene and contact precautions are imperative, as is ongoing research into more effective antimicrobial agents.

Hypersensitivity to plasma exchange in a patient with thrombotic thrombocytopenic purpura.

To a limited extent, thrombotic thrombocytopenic purpura (TTP) in addition to its clinical features is being defined nowadays with laboratory tests such as the assay for the Von Willebrand factor-cleaving protease (ADAMTS 13) and its antibody. We present a case report of a patient with TTP and idiopathic thrombocytopenic purpura (ITP) who had an elevated inhibitor level after plasma exchange. After instituting plasma exchange, patient improved clinically with a platelet count in the normal range. Subsequently, she developed an elevated ADAMTS antibody titer accompanied by a decline in platelet count despite continued exchange. She was successfully treated with a combination of steroids, rituximab and increased dose plasmapheresis. Based on this experience, we conclude that a drop in platelet count while patient is undergoing plasma exchange especially in an initial episode of TTP needs prompt institution of additional therapy to improve outcomes. This case also brings to attention the possibility of an underlying ITP in a patient with an initial diagnosis of TTP.

Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes.

PURPOSE: Epigenetic modulation of gene expression plays an important role in cancer, including leukemia. Furthermore, histone deacetylase inhibitors may induce the reexpression or repression of genes critical for normal hematopoiesis. The purpose of this study was to evaluate the toxicity, pharmacokinetic profile, and selected pharmacodynamic properties of the histone deacetylase inhibitor depsipeptide in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML). EXPERIMENTAL DESIGN: Depsipeptide was administered to MDS or AML patients at a (solid tumor) phase I dose of 18 mg/m(2) i.v. on days 1 and 5 every 3 weeks. Toxicities and clinical activity were monitored and pharmacokinetic and pharmacodynamic studies were done. RESULTS: Twelve patients (nine with AML, three with MDS) received one to five cycles of depsipeptide. The most common grade 3/4 toxicities were febrile neutropenia/infection (five patients), neutropenia/thrombocytopenia (nine patients), nausea (nine patients), and asymptomatic hypophosphatemia (three patients). No clinically significant cardiac toxicity was observed. The best response of 11 assessed patients was one complete remission in a patient with AML, stable disease in six patients, and progression of disease in four patients. Exploratory laboratory studies showed modest but rapid increases in apoptosis and changes in myeloid maturation marker expression. Histone H3 and H4 acetylation levels were evaluated in five patients; no consistent changes were observed. CONCLUSION: Depsipeptide therapy can be administered with acceptable short-term toxicity. However, gastrointestinal symptoms and fatigue seem to be treatment-limiting after multiple cycles. Depsipeptide monotherapy has limited clinical activity in unselected AML/MDS patients.