Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders

Although nonmyeloablative conditioning regimen transplantations (NMTs) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality. In vivo T-cell depletion, using alemtuzumab, has been shown to reduce the incidence of GVHD. However, this type of maneuver, although reducing GVHD, may have an adverse impact on disease response, because NMTs exhibit their antitumor activity by relying on a graft-versus-malignancy effect. To explore the efficacy of alemtuzumab compared with methotrexate (MTX) for GVHD prophylaxis, we have compared the results in 129 recipients of a sibling NMT enrolled in 2 prospective studies for chronic lymphoproliferative disorders. Both NMTs were based on the same combination of fludarabine and melphalan, but the United Kingdom regimen (group A) used cyclosporin A plus alemtuzumab, whereas the Spanish regimen (group B) used cyclosporin A plus MTX for GVHD prophylaxis. Patients receiving alemtuzumab had a higher incidence of cytomegalovirus (CMV) reactivation (85% versus 24%, P <.001) and a significantly lower incidence of acute GVHD (21.7% versus 45.1%, P =.006) and chronic GVHD (5% versus 66.7%, P <.001). Twenty-one percent of patients in group A and 67.5% in group B had complete or partial responses 3 months after transplantation (P <.001). Eighteen patients in group A received donor lymphocyte infusions (DLIs) to achieve disease control. At last follow-up there was no difference in disease status between the groups with 71% versus 67.5% (P =.43) of patients showing complete or partial responses in groups A and B, respectively. No significant differences were observed in event-free or overall survival between the 2 groups. In conclusion, alemtuzumab significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving alemtuzumab often required DLIs to achieve similar tumor control but the incidence of GVHD was not significantly increased after DLI.     

Efficacy of Preoperative Radiation Therapy for Resectable Rectal Adenocarcinoma When Combined With Oral Tegafur-Uracil Modulated With Leucovorin

PURPOSE: The aim of this study was to evaluate the efficacy of preoperative radiation therapy for resectable rectal adenocarcinoma (T3-T4) when delivered in combination with chemotherapy (oral tegafur-uracil modulated with leucovorin). METHODS: Thirty-eight patients (23 males; mean age, 62 years.) with histologically proven rectal adenocarcinoma with primary tumor clinical classification T3-T4 (resectable) and N0 or N1-N2, according to TNM staging system, took part in the present clinical trial. After tumor and metastasis resectability confirmation, radiation therapy was administered by delivering a dose of 45 Gy in 25 fractions for 5 weeks. Chemotherapy treatment was initiated on the same day as radiotherapy and consisted of intravenous infusion of 6S-steroisomer of leucovorin 250 mg/m2/day in 2 hours on Day 1, followed by oral 350 or 300 mg/m2/day of tegafur (a 5-fluorouracil prodrug) plus uracil on Days 1 to 14 divided into 2 daily doses, and oral 6S-steroisomer of leucovorin 7.5 mg/12 hours on Days 2 to 14, with a total of 102 courses of neoadjuvant chemotherapy (i.e., mean of 2.7 courses per patient). Six additional courses of tegafur-uracil were given postoperatively to all 38 patients but 1 who refused. RESULTS: As a result of preoperative chemoradiation treatment, 4 (10.5 percent) complete responses, 20 (52.6 percent) partial responses, and 14 (36.8 percent) patients with disease stabilization were observed. No patients had preoperative disease progression. Histologically proven downstaging was observed in 23 (60 percent) patients. On initial evaluation, only 39 percent of patients were considered as being good candidates for sphincter-preserving surgery; however, on preoperative chemoradiation completion this figure increased up to 60 percent. For the 23 patients eventually undergoing sphincter-preserving surgery, postoperative sphincter function assessment showed excellent function in 15 (65 percent) patients, good in 5 (22 percent), fair in 2 (9 percent), and poor in 1(4 percent). With a median follow-up of 37 (range, 10–62) months, local failure was found in 3 (8 percent) patients and distant failure in 2 (5 percent). Three-year actuarial disease-free survival and 3-year overall survival rates were 83 and 90 percent, respectively. Local control rate was 92 percent. Toxicity and postoperative complication rates were reasonable. CONCLUSIONS: Our neoadjuvant radiation therapy protocol is efficient for the preoperative treatment of resectable rectal adenocarcinoma when combined with chemotherapy (oral tegafur-uracil modulated with leucovorin). However, this protocol needs to be tested in a phase-III clinical trial with a larger sample size.     

Angina related to 5-Fluorouracil

Treatment with 5-fluorouracil is common in oncological patients. Side effects on bone marrow, skin, and mucous membranes have been reported. Cardiotoxicity, which is less predictable, can be life-threatening. Manifestations include angina, arrhythmias, infarction, heart failure and cardiogenic shock. The toxic mechanisms that might be involved have been much discussed but have not yet been clearly established. Current evidence supports the possibility of a metabolic effect in common with the cascade secondary to ischemia due to coronary disease. Based on a case report, we discuss the usual clinical presentation, treatment and prognosis. Finally we make recommendations for managing patients being treated with 5-fluorouracil.     

Treatment of a giant coronary aneurysm with a novel technique: scaffolding (tunnel) stenting to support PTFE-covered stents: insights from intravascular ultrasound

This report describes a patient with progressive angina and a giant coronary aneurysm in the right coronary artery. Percutaneous treatment was performed using a novel technique consisting of implantation of a long stent that provided scaffolding or bridge for the subsequent implantation of two polytetrafluoroethylene-covered stents. Complete closure of the aneurysm was successfully achieved. In the angiogram performed 3 months later for recurrent angina, a localized narrowing at the distal stent edge (corresponding to severe underexpansion of the stent struts on intravascular ultrasound) was observed. This was successfully treated with balloon angioplasty. The technical details of this new technique are described.     

Evaluating the risk of HIV transmission through unprotected orogenital sex

We analysed a cohort of heterosexual HIV- serodiscordant couples with the aim of evaluating the risk of transmission ascribed to unprotected orogenital intercourse. A total of 135 seronegative individuals (110 women and 25 men), whose only risk exposure to HIV was unprotected orogenital sex with their infected partner, registered 210 person-years of follow-up. After an estimated total of over 19,000 unprotected orogenital exposures with the infected partner not a single HIV seroconversion occurred.     

Comparación de los efectos inducidos sobre la calciuria por tiazidas y diferentes dosis de sal en la dieta: implicaciones en la práctica clínica

Introduction

Both dietary restriction of sodium chloride (NaCl) and treatment with thiazides have been used in hypercalciuric patients.

Blood pressure and urinary excretion of electrolytes in Spanish schoolchildren

Despite the importance of hypertension in adults, its effects on child health are poorly understood. This cross-sectional epidemiological study was designed to look for a relationship between elevated blood pressure (BP) in children and 24-h urinary excretion of sodium (Na) and potassium (K), and between BP and dietary salt intake. The study population was all 59 856 schoolchildren aged 6 to 14 years in the province of Almería in southern Spain, among whom 613 participants were chosen randomly for study. We measured 24-h urinary Na and K concentrations, systolic and diastolic BP, body weight and height. There was a weak correlation between Na excretion and systolic BP (r = 0.18, 95% confidence interval 0.10-0.26), and between K excretion and systolic BP (r = 0.49, 95% CI = 0.04-0.20). Body weight was the variable that best correlated with systolic (r = 0.49, 95% CI = 0.43-0.55) and diastolic BP, and with Na excretion (r = 0.48, 95% CI = 0.42-0.55). Multiple regression analysis also showed that body weight was the variable that best correlated with systolic BP (b = 0.58), although the variables in the equation explained little of the total variability in BP (26%). These correlations were significant at P < 0.05. In conclusion urinary electrolytes correlated poorly with BP in a sample of Spanish schoolchildren. Body weight was the only variable that showed a weak relationship with BP and Na excretion.