J.P. Donnelly

Febrile mucositis in haematopoietic SCT recipients.

We undertook a retrospective analysis of a cohort of 67 patients with multiple myeloma who had received an autologous haematopoietic SCT (HSCT) following high-dose melphalan to explore the impact of mucositis on the systemic inflammatory response. A homogenous group of 16 patients without a documented infection and a group of 30 patients with bacteraemia were identified for whom complete data on neutropenia, an inflammatory response, infectious complications and mucositis were available. All patients showed a similar course of events with an inflammatory response coinciding with the occurrence of significant mucositis, regardless of the presence or absence of infection. The only differences between the two groups were significantly higher maximum C-reactive protein (CRP) levels and lower citrulline levels for patients with bacteraemia, suggesting a causative role for mucositis in the occurrence of bacteraemia. Statistical analysis showed a significant association over time between citrulline levels, to a lesser extent bacteraemia, but not neutropenia, and the inflammatory response measured by CRP. These data suggest that the inflammatory response after conditioning for a HSCT is the result of the chemotherapy-induced mucositis and independent of neutropenia. Though primary inflammation appeared due to mucositis, infections resulting from mucosal barrier injury and neutropenia aggravated the inflammatory response.

Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated.

Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated

Reduced PTLD-related mortality in patients experiencing EBV infection following allo-SCT after the introduction of a protocol incorporating pre-emptive rituximab

The mortality associated with post-transplant lymphoproliferative disorder (PTLD) induced by EBV infection can be reduced by monitoring EBV by polymerase-chain-reaction and rituximab given pre-emptively. We performed a retrospective analysis of the risk factors for the occurrence of EBV infection/disease and EBV-related mortality among 273 consecutive recipients of a T-cell-depleted allo-SCT during two periods: (a) before the implementation of a comprehensive protocol (2006–2008) and (b) afterwards (2009–2011). EBV infection was detected in 61 (22%) cases, and 28 cases were considered to have had EBV disease. Treatment with antithymocyte globulin was the most important risk factor (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.3–4.2, P=0.001). After implementation of the protocol, in patients experiencing EBV infection, pre-emptive therapy was started more often and sooner (median 3 vs 6 days, P=0.002). Moreover, there were fewer cases of monomorphic PTLD (4/33 (12%) vs 11/28 (39%), P=0.01), and the EBV-related mortality was lower for patients experiencing EBV infection (2/33 (6%) vs 8/28 (29%), OR 0.2; 95% CI 0.05–0.9, P=0.03). The EBV protocol proved feasible and resulted in faster initiation of pre-emptive therapy, the diagnosis in an earlier stage of EBV disease, and decreased EBV-related mortality.

Safe living after hematopoietic cell transplantation.

Brigham & Women’s Hospital and Dana-Farber Cancer Institute, Boston, MA, USA; University of Washington Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Division of Infectious Disease, Washington University School of Medicine, St Louis, MO, USA; Children’s Hospital Boston, Boston, MA, USA; Hospital General Universitario Gregorio Maranon, University of Madrid, Madrid, Spain; National Institutes of Health, Bethesda, MD, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA; Division of Infectious Disease, University of Minnesota, Minneapolis, MN, USA and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Genetic variants and the risk for invasive mould disease in immunocompromised hematology patients.

Purpose of review Single-nucleotide polymorphisms (SNPs) appear to influence the risk of invasive mould disease (IMD) in immunocompromised patients. This raises the question of whether genetic risk prediction can be used to alter clinical practice. This review focuses on the current status of genetic association studies regarding invasive fungal disease among hematology patients, with an emphasis on IMD. Recent findings Many studies have shown that SNPs in genes encoding cytokines, chemokines, and their receptors can increase the risk for IMD. Greater emphasis has recently been placed on SNPs in pattern-recognition receptors, including Toll-like receptor 4 (TLR4) and dectin-1. An association has been found between SNPs in TLR4 and dectin-1 and invasive aspergillosis, which has been strengthened by biological evidence from in-vitro and in-vivo studies that showed a loss of function in the presence of the SNP. Nevertheless, despite improving our understanding of host antifungal defenses in immunocompromised hosts, clinical applicability is still a long way off. Current genetic associations need further validation, as virtually all studies suffer methodological limitations such as small sample size, heterogeneity of cohorts, selection bias, ill defined outcome measure, and statistical flaws, mainly the lack of adjustments for multiple comparisons. Summary Genetic variations in immune genes are associated with the risk for IMD among hematology patients although inconsistencies are frequently reported. The next step will be to select consistent SNPs and test them for their value in assessing risk in larger, better designed multicenter studies that will necessitate collaboration of multiple institutions in national or international consortia.

Incidence of and risk factors for persistent gram-positive bacteraemia and catheter-related thrombosis in haematopoietic stem cell transplantation

A cohort of 439 haematopoietic SCT recipients was analysed to determine the incidence of Gram-positive coccal bacteraemia and thromboembolic events associated with the use of central venous catheters (CVCs) and to determine risk factors for these complications. The incidences of persistent coagulase-negative staphylococcal (CoNS) bacteraemia, symptomatic thrombosis and thrombophlebitis were 25%, 9.6% and 6.6%, respectively. Duration of neutropenia (in days, odds ratio (OR) 1.02; P=0.04) and left-sided placement of the CVCs (OR 1.73; P=0.03) were independent risk factors for the occurrence of persistent CoNS bacteraemia, whereas the use of less mucotoxic conditioning regimens was associated with a lower risk (high-dose melphalan (HDM)/BEAM vs other regimens, OR 0.24; P<0.001). Use of TBI, persistent CoNS bacteraemia and tip colonisation were all significantly associated with an increased risk of symptomatic thrombosis (OR 6.03, 3.36 and 2.80, respectively; P⩽0.02). The risk factors found in this cohort of SCT recipients differed from those found in the general cancer population, showing an important role for persisting bacteraemia in the pathogenesis of CVC-associated thrombosis. Therefore, we constructed a new algorithm in order to improve catheter management and prevent these CVC-related complications.

Impact of palifermin on intestinal mucositis of HSCT recipients after BEAM

The matched-control study failed to show a clinical relevant impact of palifermin on intestinal mucositis, although there was a reduced inflammatory response and less febrile neutropenia among patients who had no bacteraemia.