Early splenectomy and polychemotherapy versus polychemotherapy alone in chronic myeloid leukemia

The effect of early splenectomy and of polychemotherapy with hydroxyurea, busulfan, and alternate bimonthly courses of arabinosyl cytosine and vincristine plus prednisone, was evaluated in 139 previously untreated patients with chronic myeloid leukemia (CML), consecutively admitted to 18 hospitals from March 1973 to October 1974. Fifty-six patients were splenectomized and 83 patients were not splenectomized. Splenectomy did not influence the duration of chronic and blastic phase, and did not prolong survival. The prognosis of high risk patients was not improved. During the chronic phase, high platelet counts were more frequent in splenectomy group, and five patients developed thrombotic or thromboembolic complications, 5 to 19 months after the operation. The median survival of the whole group was 50 months, with 32 of 139 patients (actuarial proportion 30%) remaining alive 72 months after diagnosis, but the slope of the survival curve was similar to that of historical controls. The results of this trial suggests that new strategies should be developed for the therapy of CML.     

Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study.

OBJECTIVES: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship.METHODS: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately.RESULTS: Recent consumption (at reference age minus two) of >/=7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3).CONCLUSIONS: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact.     

Short-term effects of bimatoprost in glaucoma patients from an outpatient clinic.

PURPOSE: A drug utilization trial was performed to investigate acute versus short-term effects after switching or adding bimatoprost in open-angle glaucoma patients over a 3- month observation period. METHODS: One (1) eye was randomly chosen from 47 glaucomatous patients (abnormal visual field and/or abnormal optic nerve and intraocular pressure (IOP) above 21 mmHg without treatment). Only patients who did not reach the target IOP with their ongoing treatment were recruited in this study. IOP was measured at baseline, after 1 hour, and 2 hours from the first instillation and after 1 week, 1, and 3 months of treatment. RESULTS: The IOP before bimatoprost administration was 20.16+/-3.6 mmHg (mean+/-standard deviation). There was no statistically significant decrease of IOP after 1 hour (mean IOP, 19.96+/-4.25 mmHg) and after 2 hours (mean IOP, 17.73+/-3.24 mmHg). Statistically significant (p<0.001) decreases after 1 week (mean IOP, 16.48+/-2.9 mmHg), after 1 month (mean IOP, 16.48+/-2.9 mmHg) and after 3 months (mean IOP, 16.15+/-2.7 mmHg) were found. CONCLUSION: The results suggested that bimatroprost had a significant acute effect on IOP in monotherapy, while no significant effect was found when the therapy was switched or added. The effect for primary open-angle glaucoma was very evident. There was no specific side effect attributable to combining bimatoprost with any of the treatments in use.     

ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia.

PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.     

Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.     

Sport activities and exercise as part of routine cancer care in children and adolescents

The burden of morbidities affecting cardiovascular and musculoskeletal systems, metabolism, and psychosocial health in young patients with cancer is high. It is alarming that patients and survivors of childhood cancer are less physically active than their healthy peers, since exercise may improve many of these conditions significantly and is associated with reduction in all‐cause mortality in the general population. Systematic integration of exercise programing into cancer care remains an exception, above all in children. Pediatric oncologists may contribute to a culture shift towards educating patients and stakeholders on the benefit of exercise and sports for children and adolescents with cancer.     

Estimation of Nanoporous Au Young’s Modulus from Serial Block Face-SEM 3D-Characterisation

Nanoporous Au has been subjected to serial block face-scanning electron microscopy (SBF-SEM) 3D-characterisation. Corresponding sections have been digitalized and used to evaluate the associated mechanical properties. Our investigation demonstrates that the sample is homogeneous and isotropic. The effective Young’s modulus estimated by an analytical multiscale approach agrees remarkably well with the values stated in the literature.