The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the ...question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35-59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.
Bacillus subtilis is a gram-positive, aerobic, spore-forming soil bacterium ubiquitous in the environment. The beneficial effects of B. subtilis spores on the balance of the intestinal microflora is ...the rationale for its general use as a probiotic preparation in the treatment or prevention of intestinal disorders. B. subtilis spores are available in Italy as a pharmaceutical preparation for oral use. Each dose contains a mixture of 10 super(9) spores of four distinct antibiotic-resistant derivatives of ATCC 9799 (Enterogermina; distributed by Sanofi Winthrop, Milan, Italy) per vial. The pathogenic potential of B. subtilis is generally described as low or absent. Data on the general importance of infections due to B. subtilis are incomplete, since it is a general practice of most microbiological laboratories to discard these strains or to report them as contaminants. Also, in the cause-of-death statistics of the World Health Organization no data on B. subtilis infections are present since, even if reported, they would be "invisible" at the international comparative level due to the coding used for classification of death causes. In the literature, only a few cases of infections due to B. subtilis are reported and only one retrospective study describes the isolation of antibiotic-resistant strains of B. subtilis.
In recent years fludarabine alone or in combination with other drugs has been reported to be effective in the treatment of B-cell chronic lymphocytic leukemia (B-CLL), both as first line and salvage ...therapy. Among the different combination regimens, the association of fludarabine and cyclophosphamide has shown a considerable therapeutic efficacy, although a relevant number of infectious complications have been described, particularly in elderly patients. The aim of this work was to evaluate the efficacy, the toxicity, and the incidence of infectious episodes of a regimen combining lower doses of fludarabine and cyclophosphamide in elderly patients with B-CLL refractory to conventional therapy.
Twenty patients with progressive B-CLL with a median age of 75 years (4 in stage B and 16 in stage C) and refractory to conventional therapy were enrolled in this study. The combination regimen was as follows: fludarabine 15 mg/m2/day i.v. max 25 mg and cyclophosphamide 200 mg/m2/day i.v. for four days.
All patients enrolled were evaluable for response. Three out of 20 (15%) patients achieved a complete remission (CR), 14/20 (70%) a partial response (PR) with an overall response rate (CR+PR) of 85%, according to National Cancer Institute-Working Group response criteria. Three patients were considered resistant. In four out of 20 patients (20%), a severe neutropenia (neutrophils < 0.5x10(9)/L) occurred and one of them developed an infectious complication which required treatment with systemic antibiotics and granulocyte colony- stimulating factor (G-CSF). Non-hematologic toxicity was negligible in all patients but one, who despite a adequate therapy with allopurinol and hydration, experienced a tumor lysis syndrome with transient but severe renal impairment.
The association of low-dose fludarabine and cyclophosphamide appeared to be effective in this subset of B-CLL patients, reproducing a similar overall response rate obtained with other fludarabine-based combination therapies. In addition, in this group of elderly patients, toxic side effects were negligible and infectious complications remarkably low.
The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more ...aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage.
To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period.
Young adults (YAs: 18–29 years old) significantly differed from adults (30–59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011).
The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome.
NCT00510926, NCT00514488, NCT00769327, NCT00481052.
The aim of this study was a retrospective analysis of the presenting features of extramedullary plasmacytoma, its response to therapy and its clinical course.
Forty-six cases diagnosed between August ...1970 and June 1993 were carefully reviewed. The follow-up was continued until June 1998 and the median observation time was 118 months.
The disease was most frequently localized in the upper airways (37/46; 80%), with the mass limited to a single site in all but seven patients in whom two contiguous sites were involved. Other localizations were the lymph nodes, thyroid, skin, stomach, and brain. The clinical symptoms were related to the site of presentation, and the median time between appearance and diagnosis was 7.5 months. The median age at diagnosis was 55 years (range 16-80), with 14 patients (30%) being under 50 years old. The disorder was approximately twice as common in males as in females. Ten patients (21%) had a monoclonal component. The therapeutic strategy varied, although the most frequent form of treatment was local radiotherapy. Thirty-nine patients (85%) achieved complete remission (CR), five (11%) a partial remission (PR) and two (4%) did not respond to therapy (NR). Local recurrence (LR) or recurrence at other sites (ROS) occurred in 7.5% and 10%, respectively. Seven patients (15%) developed multiple myeloma (MM), characterized by multiple sites of osteolysis in almost all cases with soft tissue involvement in some of them. The 15 year survival rate was 78%.
This review of a relatively large series of patients confirms the favorable prognosis of EMP when treated locally by irradiation and/or surgery.
Abstract
Objective
To look for outcomes of patients (pts) with major gastrointestinal haemorrhage (mGIH) and ongoing anticoagulants out of four-year survey of community hospital with catchment area ...197,722 inhabitants, of whom 15,267 with Warfarin (W) and 10,397 with direct oral anticoagulants (DOACs). DOACs were available for prescription in the catchment area since 4 years (dabigatran and rivaroxaban), 3 years (apixaban), and 2 years (edoxaban).
Methods
Haemorrhage (n=1,919) were submitted to propensity score matching for major bleeding; mGIH were enrolled and stratified according to ongoing W or DOACs. Primary endpoint was one-month death.
Results
Out of 476 mGIH, 73 pts received anticoagulants; 22 DOACs and 51 W; p=0.0006. Of note mGIH on W accounted for 2.7% (51/1,919) per year of pts, and 0.08% (51/15,267) of the catchment area. Conversely, mGIH on DOACs accounted as follows: dabigatran (n=10/476) 0.53%, rivaroxaban (n=6/476) 0.32%, apixaban (n=5/476) 0.35%, and edoxaban (n=1/476) 0.11% per year of pts; p=0.117. Rate of mGIH and DOACs versus (vs) rate of mGIH and W as follows: less than (−) 5 fold (2.7x100/0.53) of dabigatran vs W, p=0.004; −8 fold (2.7x100/0.32) of rivaroxaban vs W, p=0.0002; −7 fold (2.7x100/0.35) of apixaban vs W; p=0.ehz745.10188, and −25 fold (2.7x100/0.11) of edoxaban vs W; p=0.ehz745.101801. However no difference versus the catchment area per year (0.723): 0.07% (10/3,373) dabigatran, 0.04% (6/4,046) rivaroxaban, 0.08% (5/2,141) apixaban, 0.06% (1/839) edoxaban.
Overall, one-month death accounted for 10/476 (2.1%). Of note 236 mGI were from the upper tract and 240 from the lower tract. Among upper tract, 10 pts received DOACs (4 dabigatran, 4 rivaroxaban, 2 apixaban, and 0 edoxaban) and 21 received W. One-month death was 0/10 DOACs versus 1/21 W, p=0.483. Among lower tract, 12 pts received DOACs (6 dabigatran, 2 rivaroxaban, 3 apixaban, and 1 edoxaban) and 30 pts received W; one-month death was 0 for every groop. Anticoagulant reversal treatment was given to 6/22 (27%) pts with DOACs versus 18/51 (35%) with W, p=0.014; transfusion to 6/22 (27%) versus 11/51 (22%), respectively, p=0.306; admission 19/22 (86%) versus 42/51 (82%), respectively, p=0.004. Sensitivity/specificity ratio of variables and biomarkers for aggressive pharmacological approach were obtained by area under ROC curve (AUC) >0.50. PTT value >37 sec (AUC 0.57) showed sensitivity 15%, specificity 90%; INR value >1.4 (0.50), sens 15%, spec 80%. In addition, warfarin (0.49) sens 15%, spec 80%; age ≥75 years (0.48) sen 60%, spec 40%.
Gastrointestinal bleeding: flow-chart.
Conclusion
Out of four-year survey, pts with ongoing DOACs were less likely to have mGIH when compared to W.
Patients with W were more likely to receive reversal tratment; pts with DOACs were more likely to undergo admission. Short-term mortality of pts with W was higher than DOACs. Aggressive pharmacological approach should be driven by PTT, INR, ongoing warfarin, and older age.
Long-lasting results achieved in 54 patients with aggressive non-Hodgkin lymphoma treated with Pro-MACE-CytaBOM regimen were evaluated. Twenty-four out of 54 (45%) patients achieved a complete ...remission and 13 of them are still in continuous remission with a median survival of 53.5 months. Interestingly, in 16 patients with intermediate grade histology we obtained an overall response rate of 100%.
Previous evidence suggests that atrial natriuretic factor (ANF) interferes with the autonomic control of circulation. In the present study we investigated whether ANF modulates forearm ...vasoconstriction reflexly induced by cardiopulmonary receptor unloading in man. For this purpose, the hemodynamic response to -20 mm Hg lower body negative pressure (LBNP) was assessed under control conditions and during the constant infusion of alpha-human ANF (0.5 micrograms/kg bolus followed by 0.05 micrograms/kg/min) in seven normal subjects. ANF infusion resulted in a slight reduction in blood pressure and right atrial pressure, did not modify heart rate or forearm vascular resistance, but significantly potentiated the reflex increase in forearm vascular resistance during LBNP (+25 +/- 9% under control conditions vs +40 +/- 12% during ANF, p less than .05). In an attempt to clarify the mechanisms underlying the enhanced reflex vasoconstriction during infusion of ANF, in five additional subjects we demonstrated that there was a comparable vascular reflex response to LBNP under control conditions and during nitroglycerin infusion at a dose that induced a reduction in atrial pressure comparable to that observed during ANF. Finally, in seven additional subjects we found that ANF infusion did not alter the reflex hemodynamic responses elicited by carotid baroreceptor unloading induced by a +60 mm Hg increase in external neck pressure. We conclude that during the infusion of a pharmacologic dose of ANF the reflex forearm vasoconstriction in response to selective cardiopulmonary receptor unloading is potentiated. This effect does not seem to be related to the hemodynamic actions of the peptide or to interference with the sympathetic control of peripheral circulation.
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