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Angel Leon

Publications and source records attributed to Angel Leon.

7 recordsLinked to original sources

Renal insufficiency and the risk of infection from pacemaker or defibrillator surgery.

BACKGROUND: Pacemakers and implanted cardioverter defibrillator (ICD) infection rates are rising. Renal insufficiency impairs immune function and is known to increase the risk of infection following implantation of orthopedic hardware. The purpose of the current study is to characterize the risk factors for pacemaker and ICD infection and to evaluate the role of renal insufficiency in this complication. METHODS AND RESULTS: A large (n = 4,856) single center experience with pacemaker and ICD procedures was reviewed. Of these, 141 were extractions of infected devices and 76 of these patients had been implanted in the Emory system and had preimplant creatinine information available for analysis. These cases were compared to 76 control patients undergoing device implantation matched by date of implant who had no infective complications. Demographic and clinical data from both groups were compared using both univariate and multivariate analysis. The overall rate of infection was 1.5%. Patients with device infection were more likely to have congestive heart failure (CHF), be diabetic, have generator exchanges, and to take warfarin than controls. There was no difference in the prevalence of coronary disease, atrial fibrillation, steroid use, or malignancy between the two groups. Elevated creatinine (Cr > or = 1.5 mg/dL) was much more frequent in patients with infection than in controls (38% vs 12%, odds ratio 4.6, P < 0.001). Moderate to severe renal disease (GFR < or = 60 cc/min/1.73 m2) was the most potent risk factor for infection, with a prevalence of 42% in infected patients versus 13% in controls (odds ratio of 4.8). CONCLUSIONS: Renal insufficiency dramatically increases the risk of infection complicating pacemaker or ICD surgery. This association should be part of the risk-benefit consideration prior to device implantation. Additional study of more extensive perioperative antibiotic therapy in this subset of patients is warranted.

Aged↗

Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma.

We evaluated prognostic factors of melphalan/fludarabine-based dose-reduced allografts in patients with multiple myeloma. From 1998 to 2002, 120 patients with multiple myeloma were treated with melphalan/fludarabine followed by allogeneic stem cell transplantation. The cumulative risk at 1 year for treatment-related mortality (TRM) was 18% (95% confidence interval [CI], 12%-28%). In a multivariate analysis, relapse after prior high-dose chemotherapy was the most significant risk factor for TRM (hazard ratio [HR], 2.80; 95% CI, 1.16-6.74; P =.02), relapse (HR, 4.14; 95% CI, 2.04-8.38; P <.001), event-free survival (HR, 3.11; 95% CI, 1.77-5.46; P <.001), and overall survival (HR, 2.69; 95% CI, 1.35-5.35; P =.005). In addition, relapse was also significantly diminished by chronic graft-versus-host disease (GVHD) in a time-dependent Cox model (HR, 0.37; 95% CI, 0.16-0.87; P =.02). At transplantation, 8% of the patients were in complete remission, whereas 27% had progressive disease. After allografting, 49% achieved complete remission, and 38% achieved partial remission. In a subgroup of patients with chemosensitivity at transplantation and no relapse after prior high-dose chemotherapy who underwent transplantation with peripheral blood stem cells (n = 46), the cumulative risk of TRM at 1 year was only 8% (95% CI, 1%-54%). The 2-year estimated event-free and overall survival was 60% (95% CI, 42%-78%) and 75% (95% CI, 59%-91%), respectively, for related donors (n = 34) and was 81% (95% CI, 59%-100%) and 92% (95% CI, 76%-100%), respectively, for unrelated donors (n = 12).

Adult↗

Cadherin-13, a mediator of calcium-dependent cell-cell adhesion, is silenced by methylation in chronic myeloid leukemia and correlates with pretreatment risk profile and cytogenetic response to interferon alfa.

PURPOSE: Cadherin-13 (CDH13) is a newly characterized cadherin molecule responsible for selective cell recognition and adhesion, the expression of which is decreased by methylation in a variety of human cancers, indicating that the CDH13 gene functions as a tumor suppressor gene. Although defective progenitor-stromal adhesion is a well-recognized feature of chronic myeloid leukemia (CML), the role of CDH13 abnormalities has not been evaluated in this disease. PATIENTS AND METHODS: We examined the methylation status of the CDH13 promoter in 179 chronic phase (CP)-CML patients and in 52 advanced-phase samples and correlated it with mRNA expression using methylation-specific polymerase chain reaction (PCR) and reverse transcriptase PCR. RESULTS: Aberrant de novo methylation of the CDH13 promoter region was observed in 99 (55%) of 179 of CP-CML patients, and 90 of the patients failed to express CDH13 mRNA (P <.0001). Advanced-stage samples (n = 52) showed concordant methylation results with their corresponding CP tumors, indicating that CDH13 methylation was not acquired during the course of the disease. Nevertheless, absence of CDH13 expression was more frequently observed among Sokal high-risk patients (P =.01) and was also independently associated with a shorter median progression-free survival time (P =.03) and poor cytogenetic response to interferon alfa treatment (P =.0001). CONCLUSION: Our data indicate that the silencing of CDH13 expression by aberrant promoter methylation occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.

Adult↗

High dose chemotherapy and autologous stem cell transplantation in patients with peripheral T-cell lymphoma not achieving complete response after induction chemotherapy. The GEL-TAMO experience.

BACKGROUND AND OBJECTIVES: Patients with aggressive non-Hodgkin's lymphomas (NHL) who do not obtain a complete response (CR) after induction chemotherapy have a poor prognosis. However, provided they are sensitive to the first regimen of chemotherapy, 25-40% of them with a B-cell phenotype may achieve long-term survival when treated with high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT). The aim of this study was to analyze the efficacy of this therapy in the corresponding patients with peripheral T-cell lymphoma (PTCL). DESIGN AND METHODS: We retrospectively evaluated the efficacy of ASCT in 35 patients with PTCL from the GEL-TAMO registry, who did not achieve a CR to standard induction chemotherapy regimens for aggressive NHL. Thirty-one patients underwent transplantation after achieving a partial response (PR) and 4 patients were non-responders. RESULTS: Following HDC/ASCT, 23 (66%) of the patients achieved a CR, 4 (11%) a PR and in 7 (20%) cases the transplant failed. One patient was not evaluated because of early toxic death. With a median follow-up of the survivors of 37.5 months, 18 patients (51%) are alive and 15 patients (43%) are free of disease. Transplant-related mortality rate at 100 days was 11% and at 5 years the probabilities of survival, freedom from progression and disease-free survival for complete responders were 37%, 36% and 55% respectively. Pre-transplant lactate-dehydrogenase level, age-adjusted International Prognostic Index (aa-IPI) and tumor score correlated with survival. INTERPRETATION AND CONCLUSIONS: One third of the patients with PTCL who fail to achieve CR to the first chemotherapeutic regimen can be rescued with HDC/ASCT. Pre-transplant values of IPI and tumor score risk systems for aggressive lymphomas were useful to predict subsequent survival.

Adolescent↗

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.

Adult↗

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction.

BACKGROUND: Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. METHODS: We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. RESULTS: The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P<0.001). The differences in the rates of hospitalization for heart failure and of death, stroke, or hospitalization for heart failure were not significant in unadjusted analyses but became marginally significant in adjusted analyses. Dual-chamber pacing resulted in a small but measurable increase in the quality of life, as compared with ventricular pacing. CONCLUSIONS: In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing.

Aged↗