Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes

Lenalidomide, an oral immunomodulatory agent, has received approval in the USA from the Food and Drug Administration (FDA) for the management of myelodysplastic syndromes (MDS) classified by the International Prognostic Scoring System (IPSS) as low risk or intermediate-1 risk and with a deletion 5q (del(5q)) cytogenetic abnormality. Although some patients with del(5q) have a relatively good prognosis, all del(5q) patients will become transfusion-dependent at some point during the course of their disease. The results of two clinical trials in more than 160 patients with MDS have demonstrated clear therapeutic benefits of lenalidomide, with >60% of patients achieving independence from transfusion during therapy, irrespective of age, prior therapy, sex, or disease-risk assessment. The recommendations presented in this review will aid the safe administration of lenalidomide for the treatment of patients with low-risk or intermediate-1-risk MDS and a del(5q) cytogenetic abnormality, and they will help physicians avoid unnecessary dose reduction or interruption, thus assuring the best efficacy for patients.     

Comparative evaluation of different chelators in removal of calcium hydroxide preparations from root canals

Background: This study compared the efficacy of 10% citric acid, 17% EDTA and 7% maleic acid (MA) with ultrasonic agitation in the removal of calcium hydroxide (CH) from root canals. Methods: Seventy maxillary anterior teeth were enlarged to F3 using protaper files. Teeth were then divided into two groups: A and B. Group A was filled with (CH + iodoform + silicone oil) mixture and group B with CH and propylene glycol (PG). Ten teeth were divided into positive and negative control groups. The volume of CH preparations was estimated using spiral CT. After seven days, teeth in groups A and B were further divided into three subgroups based on irrigants used and CH was retrieved along with ultrasonic agitation. Volume analysis was undertaken using spiral CT. Mean percentage of CH removed was analysed using one‐way ANOVA followed by Tukey’s Honestly Significant Difference test. Results: All irrigants removed (CH + PG) completely without any difference between them (p = 0.17). Removal of (CH + iodoform + silicone oil) was significantly higher for MA and citric acid than EDTA (p < 0.001). There was no difference between MA and citric acid. Conclusions: Concentrations of 7% MA and 10% citric acid were found to be superior to 17% EDTA in the removal of (CH + iodoform + silicone oil). (CH + PG) preparation was completely removed by all the irrigants.     

Exposure to wood dust and endotoxin in small-scale wood industries in Tanzania

Workers in small-scale wood industries (SSWI) have increased risks of developing asthma and other respiratory diseases. Wood dust and microbial agents have both been suggested to play a role, but few studies have measured endotoxin exposure in SSWI in Africa. We assessed inhalable dust levels in 281 samples from 115 workers and bacterial endotoxins levels in 157 samples from 136 workers from SSWI in Dar es Salaam, Tanzania. The overall geometric mean of personal exposure was 3.3 mg/m(3); geometric standard deviation (GSD) 2.5; range 0.45-67.0 mg/m(3)) and 91 EU/m(3) (GSD 3.7; range 9-4914.8 EU/m(3)) for wood dust and endotoxins, respectively. Dust and endotoxin levels were weakly correlated (r = 0.44, n = 157, P < 0.0001). Between- and within-worker variances and percentages explained by the differences among job titles and seasons were 0.31 (9%) and 0.35 (30%), respectively, for wood dust exposure, and 0.35 (0%) and 0.35 (38%) for endotoxin exposure. Higher dust and endotoxin exposure levels were observed in the dry compared to the wet season, after correcting for differences in exposure between jobs. Carving and manual cleaning were associated with the highest dust exposures. Sewing seat covers and manual cleaning were associated with the highest endotoxin exposures. Dust and endotoxin exposure levels in SSWI are high and appropriate control measures are necessary.     

Plasma 25-hydroxyvitamin D and urinary cyclic AMP in German patients with subtotal gastrectomy (Billroth II)

In an attempt to clarify the pathogenesis of the disturbed calcium metabolism which sometimes follows partial gastrectomy, we determined plasma 25-hydroxyvitamin D (25-OH-D) concentrations and urinary cyclic 3, 5-adenosine monophosphate (cAMP) excretion in patients who had previously undergone Billroth II gastrectomy and who were without clinical evidence of bone disease. In 17 Billroth II patients plasma 25-OH-D concentrations were reduced (12.6±4.6 ng/ml, mean ±sd) compared to values in 17 control patients with diseases not affecting calcium metabolism (31.6±12.9 ng/ml,P<0.001). Urinary cAMP excretion, in part reflecting parathyroid function, was higher in 17 Billroth II patients (5.0±2.5 mol/day) than in the control patients (2.6±1.3 mol/day,P<0.001). These results suggest impaired nutrition of vitamin D and secondary hyperparathyroidism in Billroth II patients. While the cause of this phenomenon is unclear, it may contribute to the disturbance of calcium metabolism in patients who have had subtotal gastrectomy.     

Extramedullary disease in multiple myeloma: a systematic literature review

Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment. Several different definitions of EMD have been used in the published literature. We advocate that true EMD is restricted to soft-tissue plasmacytomas that arise due to hematogenous spread and have no contact with bony structures. Typical sites of EMD vary according to the phase of MM. At diagnosis, EMD is typically found in skin and soft tissues; at relapse, typical sites involved include liver, kidneys, lymph nodes, central nervous system (CNS), breast, pleura, and pericardium. The reported incidence of EMD varies considerably, and differences in diagnostic approach between studies are likely to contribute to this variability. In patients with newly diagnosed MM, the reported incidence ranges from 0.5% to 4.8%, while in relapsed/refractory MM the reported incidence is 3.4 to 14%. Available data demonstrate that the prognosis is poor, and considerably worse than for MM without soft-tissue plasmacytomas. Among patients with plasmacytomas, those with EMD have poorer outcomes than those with paraskeletal involvement. CNS involvement is rare, but prognosis is even more dismal than for EMD in other locations, particularly if there is leptomeningeal involvement. Available data on treatment outcomes for EMD are derived almost entirely from retrospective studies. Some agents and combinations have shown a degree of efficacy but, as would be expected, this is less than in MM patients with no extramedullary involvement. The paucity of prospective studies makes it difficult to justify strong recommendations for any treatment approach. Prospective data from patients with clearly defined EMD are important for the optimal evaluation of treatment outcomes.Subject terms: Myeloma, Myeloma     

Intermediate intensity conditioning regimen containing FLAMSA,treosulfan, cyclophosphamide,and ATG for allogeneic stem cell transplantation in elderly patients with relapsed or high-risk acute myeloid leukemia

Lower dosage of total body irradiation (TBI) and chemotherapy in reduced-intensity conditioning (RIC) regimens prior to allogeneic stem cell transplantation have reduced the toxicity of the conditioning and non-relapse mortality. The FLAMSA–RIC protocol for high-risk patients with acute myeloid leukemia (AML) and myelodysplastic syndrome has shown promising results in refractory disease as well as in first complete remission. Still, the RIC protocol containing 4 Gy TBI/cyclophosphamide/anti-thymocyte globulin (ATG) implicates acute toxicity mainly due to TBI preventing its usage in patients with advanced age and/or severe co-morbidities. To increase feasibility and safety of the conditioning, we substituted TBI with treosulfan. Seventeen patients with relapsed or high-risk AML and either advanced age or concomitant disease were treated within a preparative regimen containing a 4-day course of chemotherapy (FLAMSA) followed by RIC comprising of treosulfan, cyclophosphamide, and ATG. After median follow-up of 12 months, the estimated incidences of relapse and non-relapse mortality were 25% and 20%, respectively. One-year overall survival was 62%. In conclusion, FLAMSA–treosulfan/cyclophosphamide/ATG is an intermediate intensity conditioning regimen with acceptable non-relapse mortality for patients with relapsed or high-risk AML. Substituting TBI with treosulfan provides an alternative to treat elderly patients or patients with severe co-morbidities when TBI appears not feasible due to the potential of increased toxicity.