Reduced fungal contamination of the indoor environment with the Plasmair system (Airinspace)

Aspergillus spp. and other moulds cause life-threatening opportunistic infections in immunocompromised patients. Indoor contamination and construction work that liberate fungal spores are a major source of nosocomial aspergillosis. Dijon hospital is a tertiary care institution in northeast France undergoing construction work beside high-risk clinical units. To determine the impact of this activity, a surveillance programme was implemented one year before building work began in order to establish baseline levels of contamination. Air and surface fungal contamination in adult and paediatric haematology units were prospectively examined following use, or not, of a new air-treatment system with mobile Plasmair units (Airinspace). There were significant reductions in overall fungal contamination for the Plasmair treated rooms for air and surface samples in both clinical units. Plasmair treatment also significantly reduced A. fumigatus in the air. These data suggest that Plasmair units may provide an efficient method of reducing indoor fungal contamination in hospitals.     

Tandem Autologous Stem Cell Transplantation Improves Outcomes in Newly Diagnosed Multiple Myeloma with Extramedullary Disease and High-Risk Cytogenetics: A Study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Although high-dose therapy and autologous stem cell transplant combined with novel agents continues to be the hallmark of first-line treatment in newly diagnosed transplant-eligible multiple myeloma patients, the impact of tandem autologous or autologous/reduced-intensity allogeneic transplant for patients with extramedullary disease (EMD) and high-risk cytogenetics is not yet defined. Here, we analyzed clinical and cytogenetic data from 488 adult myeloma patients with EMD undergoing single autologous (n = 373), tandem autologous (n = 84), or autologous–allogeneic transplant (n = 31) between 2003 and 2015. At least 1 high-risk abnormality was present in 41% (n = 202), with del(17p) (40%) and t(4;14) (45%) the most frequent. More than 1 high-risk abnormality was found in 54%. High-risk cytogenetics showed worse 4-year overall survival (OS) and progression-free survival (PFS) of 54% and 29%, respectively, versus 78% and 49% for standard-risk cytogenetics (P < .001). Co-segregation of high-risk abnormalities did not seem to affect outcome. Regarding transplant regimen, OS and PFS were 70% and 43% for single autologous versus 83% and 52% for tandem autologous and 88% and 58% for autologous–allogeneic (P = .06 and P = .30). In multivariate analysis high-risk cytogenetics were associated with worse survival (hazard ratio [HR], 2.00; P = .003), whereas tandem autologous significantly improved outcome versus single autologous transplant (HRs, .46 and .64; P = .02 and P = .03). Autologous–allogeneic transplant did not significantly differ in outcome but appeared to improve survival, but results were limited because of small population (HR, .31). In conclusion, high-risk cytogenetics is frequently observed in newly diagnosed myeloma with EMD and significantly worsens outcome after single autologous, whereas a tandem autologous transplant strategy may overcome onset poor prognosis.     

Evolution of procalcitonin,C‐reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis

Unlike bacterial infections, the value of procalcitonin (PCT) in detecting fungal infections in leukaemia patients is not clear. To determine whether the monitoring of PCT coupled with C‐reactive protein (CRP) and fibrinogen (Fib) could be helpful in the management of pulmonary aspergillosis (IPA) or mucormycosis (PM), we retrospectively analysed the evolution of PCT, CRP and Fib levels in 94 leukaemia patients with proven/probable IPA (n = 77) or PM (n = 17) from D?12 to D12 relative to IFI onset defined as D0. Overall, 2140 assays were performed. From D?12 to D0, 12%, 5% and 1.4% of patients had PCT >0.5, 1 and 1.5 μg l^?1, respectively, while CRP was >50, 75 and 100 mg l^?1 in 84%, 70% and 57% and Fib was >4, 5 and 6 g l^?1 in 96%, 80% and 61% of cases respectively (P < 10^?7). The same trends were observed from D1 to D12. Overall, between D?12 and D12, only 6.4% of patients had PCT >1.5 μg l^?1, while CRP >100 mg l^?1 and Fib >6 g l^?1 were observed in 80% and 75% of cases respectively (P < 10^?7). In leukaemia patients, IPA or PM was accompanied by a significant increase in CRP and Fib while PCT remained low.     

Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial

Various transplantation strategies have been designed to improve the poor prognosis of adult (ages 15 to 60 years) acute lymphoblastic leukemia (ALL). The GOELAL02 trial evaluated the impact of early allogeneic bone marrow transplantation (alloBMT) or delayed unpurged autologous stem cell transplantation (ASCT) for patients who had no human leukocyte antigen (HLA)-matched sibling donor or who were older than 50 years. Inclusion criteria included at least one of the following: age older than 35 years; non-T-ALL; leukocytosis greater than 30 x 10(9)/L; t(9;22), t(4;11), or t(1; 19); or failure to achieve complete remission (CR) after one induction course. Among 198 patients, the median age was 33 years. The CR rate was 80% with vincristine, idarubicine, L-asparaginase, and randomized intravenous injection or oral steroids (P = nonsignificant [ns]). AlloBMT was performed after 2 consolidation courses while ASCT was delayed after 1 additional reinduction. Intensified conditioning regimen before transplantation included etoposide, cyclophosphamide, and total body irradiation (TBI). Median follow-up was 5.1 years. The median overall survival (OS) was 29 months, with a 6-year OS of 41%. On an intent-to-treat analysis for patients younger than 50 years, alloBMT significantly improved the 6-year OS (75% versus 40% after ASCT; P = .0027). Randomized interferon-alpha maintenance had no effect on relapse or survival after ASCT. In conclusion, the outcome of adult ALL is better after early alloBMT than after delayed ASCT.     

Treatment of acute myelogenous leukaemia in patients aged 50–65: idarubicin is more effective than zorubicin for remission induction and prolonged disease-free survival can be obtained using a unique consolidation course

From December 1987 to June 1992, 251 patients aged 50–65 with de novo acute myelogenous leukaemia (AML) were recruited to a multi-institutional randomized clinical trial. Induction therapy consisted of Ara-C (200 mg/m², continuous infusion, days 1–7) with either zorubicin (ZRB) (200 mg/m², i.v., days 1–4) or idarubicin (IDR) (8 mg/m², i.v., days 1–5). Consolidation therapy consisted of a single course of intensive chemotherapy with high-dose Ara-C (3 g/m², 3 h infusion, q 12 h, days 1–4) and m-Amsa (100 mg/m²/d, i.v., days 5–7).
The complete remission (CR) rate was (73%) with Ara-C/IDR versus (60%) with Ara-C/ZRB ( P  = 0.033). In multivariate analysis, factors found to be significant in predicting CR were normal karyotype and treatment with IDR. With a median follow-up of 73 months, the median disease-free survival (DFS) duration of all CR patients and the probability of CR at 6 years were 17 months and 29%. In multivariate analysis the only factor associated with an increased DFS duration was a normal karyotype. The median event-free survival (EFS) duration for all evaluable patients and the median overall survival duration for all eligible patients were respectively 7 and 12 months without any difference between induction arms.
The study shows that in patients aged 50–65 idarabicin is more effective than zorubicin for remission induction. However, the type of anthracycline did not influence overall survival duration. Using a unique consolidation course, we observed a prolonged DFS which compares favourably with results obtained with more prolonged consolidation therapy or maintenance treatment.     

Diagnostic value of serum IL-6 level in monoclonal gammopathies

Summary. The serum level of IL-6 was reported to reflect disease severity in patients with multiple myeloma. We used a specific radioimmunoassay to measure the level of IL-6 in 239 serum samples in which a monoclonal gammopathy was identified for the first time. The same sample was used for the measurement of serum C reactive protein and serum albumin. Then, an inventory of clinical and biological features allowed us to classify these patients into five groups: monoclonal gammopathy of undetermined significance (MGUS: 128), multiple myeloma (MM:66), Waldenström's macroglobulinaemia (WM:27), non-Hodgkin's lymphoma (NHL: 11) and chronic lymphocytic leukaemia (CLL: 7). The number of patients with serum IL-6 (S-IL-6) level >0.335 ng/ml (upper limit in normal sera) was significantly higher in the MM group (35%; Confidence Interval (CI) 23.5–46.5) compared with the MGUS group (15%; CI 8.8–21.2). The distribution of S-IL-6 levels was also significantly different between the groups (Mann-Whitney test: P< 0.01). High S-IL-6 levels were measured in 5/11 patients with NHL and 9/27 patients with WM. The distribution of S-IL-6 levels in these groups was the same as that in MGUS or MM groups. In patients with MM, elevated S-IL-6 levels were associated with haemoglobin level <100 g/l (P< 0.005). bone marrow plasmocytosis >50% (P<0.05) and stages II and III in the Durie & Salmon staging system (P< 0.005). The S-IL-6 level was also related to light chain component excretion in urine (P<0.01) and M component serum level for IgA (P<0.01). In patients with MGUS, the S-IL-6 level correlated with serum CRP level (P<0.05). serum lactate dehydrogenase (P< 0.05) and serum ferritin (P < 0.01). We conclude that the S-IL-6 level is a marker of high tumour burden in multiple myeloma. However, S-IL-6 level can be increased in patients with MGUS in relation to inflammatory parameters. Therefore the S-IL-6 level does not demonstrate high predictive value for the diagnosis of MM in patients with newly identified monoclonal gammopathy.     

Polyvisceral arteritis in chronic graft-versus-host disease: antiphospholipid-negative thrombotic syndrome mimicking polyarteritis nodosa

A case of polyarteritis is reported in an 18-year old woman, occurring 2 years after an allogeneic bone marrow transplant. The clinical manifestations were similar to those of polyarteritis nodosa (PAN) with a wide range of organs involved including life-threatening cardiac and mesenteric problems requiring plasmapheresis and intravenous immunoglobulin (IgIV).     

Intravenous itraconazole followed by oral itraconazole for the treatment of amphotericin-B-refractory invasive pulmonary aspergillosis

The efficacy and safety of 2 weeks of intravenous itraconazole (200 mg twice daily for 2 days, then 200 mg once daily for 12 days) followed by 12 weeks of oral itraconazole capsules 200 mg twice daily were evaluated in a multicentre, open trial in 31 immunocompromised patients with invasive pulmonary aspergillosis (IPA). We report on a subset of 21 patients who had amphotericin-B-refractory IPA. All patients had haematological malignancies, 10 patients had failed prophylaxis, 12 patients had failed empirical therapy and 2 patients had failed treatment of confirmed infection with amphotericin B. By the second day of treatment, all patients assessed (n = 12) had trough plasma concentrations of itraconazole greater than 250 ng/ml. Mean trough plasma concentrations increased throughout the intravenous and oral treatment periods. Of the 10 patients who completed the 14 weeks of therapy, 9 (90%) had a complete or partial response and the remaining patient had stable disease. Overall, 11 of the 21 patients (52%) had a complete or partial response at their last assessment and three additional patients had stable disease. During intravenous treatment, 18 patients (86%) experienced adverse events; during oral treatment, 11 patients (52%) experienced adverse events. Most adverse events were not related to itraconazole treatment and all were expected in this patient population. In conclusion, intravenous itraconazole followed by oral itraconazole is an effective and well-tolerated treatment for amphotericin-B-refractory IPA.