Pretransplant active disease status and HLA class II mismatching are associated with increased incidence and severity of cytokine release syndrome after haploidentical transplantation with posttransplant cyclophosphamide

Cytokine release syndrome (CRS) represents a life-threatening side effect after haploidentical stem cell transplantation (Haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). Factors predictive of CRS development is still a matter of debate. We retrospectively analyzed 102 consecutive patients receiving a bone marrow (BM) (n = 42) or peripheral blood stem cells (PBSC) (n = 60) Haplo-SCT with PT-Cy. The two cohorts were similar in main patients' characteristics besides disease type (P = .02). Cumulative incidence of grades 1, 2, and 653 CRS was 80%, 52%, and 15% at a median of 2, 4, and 7 days, respectively. Moderate/High-grade fever (39\ub0-41\ub0), grade 1 and grade 653 CRS occurred more frequently after PBSC relative to BM grafts (68% vs 33%, P = .0005; 87% vs 71%, P = .009; 20% vs 7%, P = .07). Only patients experiencing grade 653 CRS had a worse outcome in terms of 1-year overall survival (OS) and nonrelapse mortality (NRM): 39% vs 80% (P = .002) and 40% vs 8% (P = .005), respectively. By univariate analysis the only factors associated with the increased risk of 653 CRS were pretransplant disease status (8% for complete remission, 11% for partial remission, and 38% for active disease, P = .002), HLA-DRB1 mismatching (57% vs 14%, P = .007), and PBSC graft (P = .07). By multivariable analysis, only pretransplant disease status (hazard ratio, HR: 6.84, P = .005) and HLA-DRB1 mismatching (HR: 17.19, P = .003) remained independent predictors of grade 653 CRS. Only grade 653 CRS is clinically relevant for the final outcome of patients receiving Haplo-SCT with PT-Cy, is more frequent after a PBSC graft and is associated with pretransplant active disease and HLA-DRB1 mismatching

The first period of the 2002 Etna eruption (27 October-5 November): preliminary results

We report on the first period of the 2002 Etna eruption started on 27th October and ended on 5th November, occurring 15 months after the end of the 2001 eruption. Volcanological and geochemical data are presented in order to characterize the complex intrusion mechanism that contemporaneously involved the NE and S flanks of the volcano. Preliminary data outline that two distinct magma intrusions fed the eruptive fissures. Strong fire fountain activity mainly from the S fissure, produced copious ash fall in eastern Sicily, causing prolonged closure of Catania and Reggio Calabria airports. Lava emitted from the NE fissure formed a 6.2 km long lava flow field that destroyed the tourist facilities of Piano Provenzana area and part of Linguaglossa pine forest.Published1-10reserve

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia

Management of hepatitis C virus infection in liver transplantation with adacolumn apheresis

Recurrent hepatitis C virus (HCV) is a major cause of liver transplant loss, hepatic failure, and retransplantation need. Posttransplantation antiviral therapy in patients with evidence of recurrent disease is the mainstay of management. Although HCV is a hepatocellular pathogen, there is increasing evidence that the virus can infect and persist in other cells. In particular, granulocytes and monocytes/macrophages are known to constitute extrahepatic sites for HCV replication and dissemination. The aim of this study was to apply Adacolumn apheresis as a possible therapeutic alternative to conventional drug therapy to manage HCV infections. Seven patients who underwent liver transplantation for HCV-related cirrhosis were eligible for the study. The patients underwent 5 1-hour sessions for 5 consecutive days. The first treatment was performed in the anhepatic phase of liver transplantation with the intent to early reduce infected granulocytes and monocytes/macrophages. The patients were evaluated over the 5 days after inclusion with 3- and 6-months follow-ups. Early apheresis treatments in the anhepatic phase and over the following 4 days after transplantation produced low viral loads in 4 patients, negative viral loads in 2 patients, and increased viremia in 1 patient. At follow-up, the viremia load was stable in 6 patients without increased transaminase levels. At the end of the treatment cycle, almost all immune cells of the 6 patients maintained CD4+/CD8+ T-cell ratios. The optimal timing of treatment initiation is unknown, but early preemptive therapy is recommended to decrease the risk for recurrent infection. Although this study investigated the responses among a small number of patients, it documented that the Adacolumn changed cellular immunity, promoting early virologic responses. © 2012 Elsevier Inc. All rights reserved

Clinical Results of Treatment of Postsurgical Endotoxin-Mediated Sepsis With Polymyxin-B Direct Hemoperfusion

Transplant Proc. 2010 May;42(4):1021-4. Clinical results of treatment of postsurgical endotoxin-mediated sepsis with polymyxin-B direct hemoperfusion. Novelli G, Ferretti G, Poli L, Pretagostini R, Ruberto F, Perrella SM, Levi Sandri GB, Morabito V, Berloco PB. SourceDipartimento P Stefanini, Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Rome, Italy. [email protected] Erratum in Transplant Proc. 2011 Apr;43(3):942. Levi, S [corrected to Levi Sandri, G B]. Abstract We evaluated the possibility of preventing the evolution of endotoxin-mediated sepsis in severe septic shock using early treatment of critical endotoxemia with polymyxin-B direct hemoperfusion (PMX-DHP). Thirty-eight postsurgical patients who fulfilled at least 2 criteria for systemic inflammatory response syndrome were stratified on the basis of the value of the endotoxin activity assay. Seventeen patients who demonstrated high risk of endotoxin activity (or=0.6) received standard therapy plus PMX-DHP every 24 hours to lower the endotoxin activity level to less than 0.4, and the remaining 21 patients with endotoxin activity levels less than 0.6 received standard therapy only. Seven patients required 2 courses of PMX-DHP therapy, 8 required 3 courses, and 2 required 4 courses. After treatment, mean arterial pressure increased, from 69.00 mm Hg to 81.35 mm Hg (P .01); heart rate decreased, from 105.40 bpm to 78.12 bpm (P .01); white blood cell count decreased, from 20,700 cells/mm(3) to 9740 cells/mm(3) (P .01); arterial oxygen tension-fraction of inspired oxygen ratio increased, from 273.82 to 305.82 (P .01); and Sequential Organ Failure Assessment score decreased, from 7 to 4 (P .01). Length of stay was longer for transplant recipients (16 days) than for other surgical patients (8(1/2) days). All patients survived to 28-day follow-up, and 15 of 16 patients (94%) had survived at 60-day follow-up. Despite the small number of patients included in the study, the encouraging results suggest that PMX-DHP is a useful therapeutic strategy for lowering sepsis-related mortality

Pediatric acute liver failure with molecular adsorbent recirculating system treatment

Background. The prognosis of pediatric acute liver failure (PALF) has been significantly improved by emergency orthotopic liver transplantation (OLT). Since 2004, the molecular adsorbent recirculating system (MARS) has been proposed as a bridging procedure. The aim of our study was to assess its efficacy in children with PALF. Patients and Methods. Since 1999 we performed treatment of 39 fulminant hepatic failure (FHF) cases with MARS. Since September 2004 we treated 6 pediatric patients with FHF who were of mean age 10.6 years (range, 3–15 years) including 4 females and 2 males. In 3 cases the cause of FHF was unknown; in 2 cases, it was induced by paracetamol overdose; and in 1, by acute hepatitis B virus. Inclusion criteria were: bilirubin 15 mg/dL; creatinine 2 mg/dL; encephalopathy grade II; and International normalized ratio (INR) 2.5. Other estimated parameters were: AST and ALT serum levels, lactate, and urine volume. Neurological status was monitored using the Glasgow Coma Scale (GCS). Continuous MARS treatment was performed in all patients with a kit change every 8 hours. Intensive care unit (ICU) treatment was applied to optimize regeneration and to prevent cardiovascular complications. Results. We observed a significant improvement among levels of bilirubin (P .009), ammonia (P .005), creatinine (P .02), GCS (P .002), and predictive criteria and as Sequential Organ Failure Assessment (SOFA) and Pediatric End-Stage Liver Disease (PELD). Three children underwent OLT: 1 died after 5 days due to primary nonfunction and 2 children are alive after a median follow-up of 14 months. In 2 children the MARS treatment led to resolution of clinical status without liver transplantation. One child died before OLT due to sepsis and multiorgan failure. Conclusions. We concluded that application of the MARS liver support device in combination with experienced ICU management contributed to improve the clinical status in children with PALF awaiting liver transplantation

Nonmyeloablative conditioning, unmanipulated haploidentical stem cell transplantation and post-infusion cyclophosphamide for advanced lymphomas

Allo-SCT is regularly performed in advanced lymphoma. Haploidentical family donors are a valuable source of hematopoietic stem cells and transplants from these donors, using T-repleted grafts, has recently been successfully reported. We report on 49 patients with refractory lymphoma who received T-repleted haploidentical SCT with a non-myeloablative regimen and post-transplant CY. The median time to recover ANC >0.5 x 10e9.L and transfusion independent plt count >20 x 10e9.L was 20 days (range 14-38) and 26 days (range 14-395). The probability to reach ANC >0.5 x 10e9.L at 30 days was 87% and transfusion independent plt count >20 x 10e9.L at 100 days was 87%. The cumulative incidence of grade 2-4 acute GVHD (aGVHD) was 25.6% (95% confidence interval (CI): 12.9-38.3%) and the cumulative incidence of chronic GVHD (cGVHD) was 5.2% (95% CI: 0-12.4%). The median follow-up is 20.6 months (range 12-54), and the projected 2-year OS and PFS were 71 and 63%. The relapse rate was 18.7% (95% CI: 7.6-29.8%) and the median time to relapse was 4.4 months (range 1.1-8.3). At 2 years, cumulative incidence of NRM was 16.3% (95% CI: 5.9-26.8%). T-repleted Haploidentical transplantation with post-infusion CY is a feasible and effective therapy in the poor prognosis of advanced lymphoma patients

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

Unmanipulated haploidentical transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy) represents an alternative for patients with high-risk diseases lacking HLA-identical donor. Although it provides low incidences of GVHD, the efficacy of Haplo-SCT is still questioned, especially for patients with myeloid malignancies. Thus, we analyzed 60 consecutive patients with refractory (n=30) or high-risk CR (n=30) AML or myelodysplastic syndromes (MDSs) who underwent PT-Cy Haplo-SCT. The median age was 57 years (22-73 years), hematopoietic cell transplantation comorbidity index was 653 in 38 patients (63%) and Haplo-SCT was the second allogeneic transplantation for 10 patients (17%). Although most of patients received PBSC as graft source (n=48, 80%), we found low incidences of grade 3-4 acute (2%) and severe chronic GVHD (4%). Among patients with high-risk CR diseases, 1-year non-relapse mortality, cumulative incidence of relapse, progression-free and overall survivals were 20%, 32%, 47% and 62%, respectively. In patients with refractory disease, corresponding results were 34%, 35%, 32% and 37%, respectively. We conclude that PT-Cy Haplo-SCT could provide promising anti-leukemic effect even in the setting of very advanced diseases. Thus, it represents a viable alternative for high-risk AML/MDS patients without HLA-identical donor