Showing papers by "J.P. Donnelly published in 2005"

Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients

Abstract: We noted a significant increase of interleukin-8 (IL-8), LBP and CRP mirroring the pattern of mucosal barrier injury as measured by gut integrity (lactulose/rhamnose ratio), daily mucositis score (DMS) and serum citrulline concentrations of 32 haematopoietic stem cell transplant (HSCT) recipients following intensive myeloablative therapy. Concentrations of IL-8, LBP and CRP were already significantly elevated before the onset of fever or bacteraemia due to oral viridans streptococci (OVS) in the first week after transplant during profound neutropenia. These markers reached their peak when citrulline concentrations reached their nadir, the highest scores of DMS were attained and when there was significantly decreased gut integrity. This suggests that the degree of mucosal barrier injury rather than bacteraemia due to OVS determines the intensity of the inflammatory response.

Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant

Abstract: We determined gut mucosal barrier injury (MBI) among 129 recipients of an allogeneic or autologous haematopoietic stem cell transplant (HSCT) who had been given different myeloablative regimens by measuring integrity using the lactulose/rhamnose (RHA) ratio and absorption using the ratios of rhamnose/3-O-methylglucose and xylose/3-O-methylglucose. Regimens that did not contain idarubicin induced oral mucositis and disturbed gut integrity and absorption earlier than did those containing the anthracycline. By contrast, regimens containing idarubicin induced more severe and prolonged oral and gut MBI. Gut integrity and absorption of most patients were still abnormal at discharge from hospital. These results confirm that the integrity and absorptive capacity of the gut is affected adversely by myeloablative regimens in general, although only two patterns of mucosal injury emerged depending on whether or not idarubicin was used.

A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients

Abstract: We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.

Microbiologic consequences of new approaches to managing hematologic malignancies.

Abstract: Opportunistic infections have always been pitfalls on the road of progress in the treatment of diseases that are accompanied by compromised host defences. Because of the severe morbidity and mortality associated with these infections, they have become substantial challenges for the clinicians who offer such patients care. With medical progress, the number of immunocompromised patients is still steadily climbing and it has become evident that deficiencies in host defences mechanisms are multiple as well as changing in harmony with alterations in treatment modalities for underlying diseases. Under normal circumstances, the intact epithelial surfaces of the gastrointestinal tract will prohibit invasion by micro-organisms and the mucociliary barrier of the respiratory tract prevents aspiration of fungal cells and spores, while, in contrast, dead or damaged tissue creates a nidus for infection. It is, however, questionable whether transmigration of organisms inevitably leads to infection. With the growing use of potent immunosuppressive purine analogues, fludarabine, pentostatin and cladibrine, and anti-T and anti-B cell antibodies, such as rituximab and campath, in the management of lymphoreticular malignancies, in combination with increasing emphasis on dose intensity, the number of patients at risk has almost reached levels encountered in recipients of allogenic stem cell grafts as a consequence of long-lasting deficiencies in the cellular immunity. The spectrum of opportunistic pathogens are shifting as anti-leukemic and anti-lymphoma therapy become more intensive and bone marrow transplant practices evolve. Recent studies demonstrate, that patients treated with nonmyeloablative allogeneic transplantation (or "minitransplants") to reduce transplant-related toxicity, are at high risk of contracting a serious infections. Initially bacterial infections were most problematic. However, as strategies to control bacterial infections improved, viruses demanded more attention from the clinicians but the associated morbidity declined due to advances in rapid diagnostics and the introduction of effective antivirals such as acyclovir and ganciclovir. Next to viruses, resistant bacteria, particularly Gram-positive organisms like enterococci and methicillin-resistant staphylococci urged to vigilance. It was obvious that enhanced use of antibacterials inevitably will be accompanied by selection and induction of resistant organisms. Today, opportunistic fungi have become the most frequent and dangerous pathogens. Since the 1980's the rate of nosocomial invasive fungal diseases has doubled without any sign of slowing at the turn of the millenium. During the past decades we have even observed an increased incidence of invasive fungal infections in patients who are not in an end stage of their underlying disease. Yeasts and moulds rank amongst the most frequently isolated pathogens. The relative incidence of the various fungal infections depends on geography as well as on medical practices and local conditions. Candida Aspergillus species remain the prominent fungal pathogens but more rare species are increasingly cultured.

Improved diagnostics in invasive aspergillosis and systematic monitoring in patients at high risk of infection

Abstract: Invasive aspergillosis remains an important cause of morbidity and mortality in patients with prolonged and severe immune suppression such as following haematopoietic stem-cell transplantation. Consensus definitions, which allow categorisation of patients based on diagnostic criteria, are an important improvement in uniform registration of invasive mycoses in clinical trials. Prospective monitoring of high-risk patients for the circulating aspergillus cell-wall component galactomannan, results in earlier diagnosis in two-thirds of patients when compared with conventional diagnostic methods. High-resolution CT (HRCT) enables the lesions characteristic of invasive mycoses to be detected earlier and better than by chest radiograph. In addition, invasive mycoses cause characteristic lesions on the HRCT scan including the halo-sign and the air-crescent sign. The pre-emptive management strategy which combines monitoring of patients for surrogate markers with a HRCT scan appears to be a promising approach to the early identification and treatment of patients with invasive aspergillosis.