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Objectives: AML‐2003 study sought to compare the long‐term efficacy and safety of IAT and IdAraC‐Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy. Methods: Patients were randomized to receive either IAT or IdAraC‐Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively. Results: A total of 356 AML patients with a median age of 53 years participated in the study. Long‐term overall survival (OS) and relapse‐free survival (RFS) were both 49% at 10 years. The median follow‐up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p <.001). Conclusions: Intensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to explore the incidence, microbiological etiology and outcome of febrile neutropenia among adult hematological patients following autologous stem cell transplantation (ASCT). Methods: The study population consisted of patients who received ASCT between 1 December 2006 and 30 November 2012. The epidemiology was compared to a retrospective series covering eleven previous years at the same institution. Non-Hodgkin lymphoma (NHL) patients, who had been identified as a risk group in the retrospective study, received ciprofloxacin prophylaxis from January 2008. Results: Altogether, 142 out of 178 of the included patients (80%) developed febrile neutropenia. The blood cultures were positive in 24 cases (17%). Of all bacteremia’s, 88% were caused by Gram-positive and 12% by Gram-negative bacteria. The number of Gram-negative bacteremia were significantly lower in the prospective study compared to the retrospective study (3/142, 2.1% vs. 23/265, 8.7%, p = .01). Pseudomonas aeruginosa was prevalent in the retrospective series but not discovered in the present series. Enterococcus faecium was found more frequently in the prospective study (6/142, 4.2 vs. 2/265, 0.8%, p = .02). The infectious mortality among patients with febrile neutropenia was 4/142 (2.8%) in the present series and 9/265 (3.4%) in those who received ASCT in 1996-2006. Conclusion: Most patients who received ASCT developed febrile neutropenia and a minority had bacteraemia. In comparison to the earlier time period, the incidence of Gram-negative bacteraemias decreased, probably due to ciprofloxacin prophylaxis in NHL patients, but simultaneously the incidence of Enterococcus bacteraemias increased. Infectious mortality during febrile neutropenia was low in both series. [ABSTRACT FROM AUTHOR]

Background: Infections greatly influence the outcome of acute myeloid leukemia (AML) patients receiving intensive treatment. The aim of this study was to establish the incidence, microbial etiology, risk factors and prognosis of bloodstream infections (BSIs) in patients with AML and compare the results with the previous treatment protocol (AML-92). Methods: Registery data were gathered prospectively from 357 patients aged 16–65 years recruited on the AML-2003 treatment protocol between November 2003 and November 2011 during different treatment cycles. Results: Blood culture data were available on 977 treatment episodes, in which there were 503 BSIs (51%). The overall incidence rate (IR) for BSIs (per 1000 hospital days) was 16.7. Twenty patients (5.6%) died due to an infection and 16 of them (80%) had a BSI. The most commonly detected microbes (polymicrobial episodes included) in blood cultures were coagulase-negative staphylococci (CoNS, 24.7%), viridans group streptococci (VGS, 19.1%), enterococci (13.9%) and Enterobacteriacae group (25.9%). The etiology of BSIs varied greatly from treatment cycle to cycle. Conclusions: Enterococcal BSIs have increased compared to our previous treatment protocol, and they represent significant pathogens in blood cultures. Infection-related mortality has decreased despite the increase in the IR of BSIs. Enterococci seem to be an increasingly prominent pathogen underlying BSIs in the AML patients, especially during induction therapy (20%). [ABSTRACT FROM AUTHOR]

The article reports that since 1991, Enterococcus faecium have been listed as the second leading nosocomial pathogen and are among the five most common causative agents of bloodstream infections.The issue of the emergence of Enterococcus faecium as a significant clinical problem at an adult haematology ward is discussed.

Limited data is available about the factors affecting early immune recovery or its clinical significance after autologous stem cell transplantation (auto-SCT). We prospectively analyzed factors affecting early immune recovery and outcome among 72 non-Hodgkin lymphoma (NHL) patients. Absolute lymphocyte count 15 d after auto-SCT (ALC-15) ≥ 0.5 × 109/L was associated with the use of plerixafor (p = 0.004), the number of CD34+cells (p = 0.015), and CD34+CD38−cells (p = 0.005) in the grafts. ALC-15 ≥ 0.5 × 109/L was associated with improved overall survival (p = 0.021). In patients with aggressive histology, ALC-15 ≥ 0.5 × 109/L was beneficial in regard to both progression-free survival (p = 0.015) and overall survival (p = 0.002). Early immune recovery seems to be important in transplanted patients with NHL and, therefore, an easy and affordable method for disease-related risk analysis. Patients with aggressive histology and slow immune recovery may need additional post-transplant treatment. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation is commonly used to treat non-Hodgkin's lymphomas (NHLs). Cellular composition of the blood grafts apparently has a role in the posttransplant hematologic and immune recovery. Plerixafor increases the mobilization of CD34+ cells and higher amounts of various lymphocyte subsets have been reported in the grafts. Limited prospective data are available in regard to graft cellular composition, hematologic and immune recovery, and patient outcomes in NHL patients who receive plerixafor added to chemomobilization.Study Design and Methods: Forty-one patients with NHL participated in this prospective study. All patients received chemomobilization and 15 poor mobilizers also received plerixafor. CD34+ cell subsets and lymphocyte subsets of cell grafts, posttransplant hematologic and immune recovery, and outcome were evaluated.Results: Blood grafts in the plerixafor group contained a significantly higher proportion of CD34+133+CD38- cells and more lymphocytes of all major subsets except B lymphocytes. Neutrophil engraftment was comparable and platelet recovery slightly slower in the plerixafor group. Natural killer cell recovery was significantly faster in patients mobilized with plerixafor. Otherwise hematologic and immune recovery as well as short-time outcome were comparable even though there was a trend for progression-free survival and overall survival benefit in the plerixafor group.Conclusions: In poorly mobilizing NHL patients, plerixafor added to chemomobilization is safe and effective. It also modifies the blood graft composition in many ways, some of which have been linked to better outcomes in previous studies. Larger sets of patients and longer follow-up are needed to see whether plerixafor-mobilized grafts are associated with superior outcome of the patients. [ABSTRACT FROM AUTHOR]

Background. Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome is poor. Material and methods. We performed a hospital-based retrospective analysis to evaluate the long-term results of the Nordic type of Bonn chemotherapy regimen in PCNSL patients. The study included 54 patients with newly diagnosed PCNSL who received chemotherapy with curative intent as their first-line treatment. Results. We found promising response rates, 76% of the patients achieving CR and 22% patients achieving PR, with corresponding two-year EFS 53% and OS 76%. However, with longer follow-up a constant pattern of relapses was observed with only one patient remaining in primary remission after 60 months. Discussion. The finding suggests that basic biological differences exist between PCNSL and systemic diffuse large B-cell lymphoma and there is a need for consolidation or maintenance therapy after achieving a remission in patients with PCNSL. [ABSTRACT FROM AUTHOR]

We compared biomarkers and their changes as predictors for bacteremia and severe sepsis during neutropenic fever after intensive chemotherapy in hematological patients. Serum C-reactive protein (CRP), semi-quantative procalcitonin, aminoterminal pro-brain natriuretic peptide (NT-proBNP), cortisol, lactate, plasma antithrombin and fibrinogen were measured daily from day 0 to day 3/day 4 in 89 neutropenic fever episodes of 65 hematological patients. The best predictors for bacteremia and gram-negative bacteremia were procalcitonin and its change, with odds ratios (ORs) and 95% confidence intervals of 2.63 (1.56-4.44) and 3.20 (1.77-5.80) for bacteremia and 4.14 (2.00-8.58) and 5.04 (2.18-11.63) for gram-negative bacteremia, respectively. For severe sepsis, the best predictors were CRP and fibrinogen, with ORs of 1.94 (1.07-3.52) and 1.92 (1.05-3.54). Factor analysis provided two predictive factors: procalcitonin-NT-proBNP-antithrombin factor predicted gram-negative bacteremia and CRP-fibrinogen predicted severe sepsis. Applying a combination of markers reflecting different aspects of infection might improve the recognition of risk for complications in patients with neutropenic fever. [ABSTRACT FROM AUTHOR]

Objective: To compare semi-quantitative procalcitonin with C-reactive protein in predicting bacteraemia in haematological patients with neutropenic fever. Methods: A total of 77 patients treated with intensive chemotherapy for haematological malignancy at Kuopio University Hospital were candidates for study entry. Eleven of these patients did not fulfil the criteria for neutropenic fever, and 66 patients were finally included. Nineteen patients had acute myeloid leukaemia and 47 had received high-dose chemotherapy supported by autologous stem cell transplant. Ninety neutropenic fever episodes in these 66 patients fulfilled the study entry criteria, with microbiological cultures, procalcitonin and C-reactive protein measurements available. Serum procalcitonin and C-reactive protein were analyzed at the onset of each neutropenic fever episode on day 0, and then daily from days 1 to 4. Results: Bacteraemia was observed in 21 episodes (23%) and the criteria for severe sepsis were fulfilled in 13 episodes (14%). Half of the bacteraemic episodes were caused by Gram-negative bacteria. The kinetics of procalcitonin and C-reactive protein were similar, with increasing levels for 2 to 4 days after the onset of fever. The procalcitonin level on days 1, 2, 3 and 4 was associated with bacteraemia and Gram-negative bacteraemia, but not with the development of severe sepsis. On day 1, a procalcitonin level above 0.5 ng/ml had a sensitivity of 57% and 70% and specificity of 81% and 77% to predict bacteraemia and Gram-negative bacteraemia, respectively. Conclusions: An elevated level of procalcitonin within 24 h after the onset of neutropenic fever predicts bacteraemia and Gram-negative bacteraemia in haematological patients. [ABSTRACT FROM AUTHOR]

Serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) is considered as a prognostic marker in patients with severe sepsis or septic shock, but no data are available on NT-proBNP kinetics in hematological patients with neutropenic fever. Altogether 70 hematological patients with neutropenic fever were included in this prospective study. NT-proBNP and C-reactive protein (CRP) were determined at the beginning of the neutropenic fever (d0) and then daily up to 3–4 days. The median NT-proBNP (interquartile range) increased from 127 (57–393) ng/L on d0 to 542 (194–1385) ng/L on d4. The increment of CRP was from 35 (17–61) mg/L on d0 to 109 (56–109) mg/L on d2. Neither serial NT-proBNP nor CRP predicted development of severe sepsis, but NT-proBNP was significantly higher in patients with previous cardiovascular disease than in those without. NT-proBNP seemed to reflect cardiac distress, but it did not help to predict the development of severe sepsis in this patient group. [ABSTRACT FROM AUTHOR]

Elevated plasma lactate and impaired lactate clearance have been associated with poor outcome in patients with severe sepsis. No data are available on the kinetics or prognostic value of plasma lactate in haematological patients with neutropenic fever. A total of 70 haematological patients with 94 episodes of neutropenic fever were included into this prospective study during the period 2006–2008. The median age of the patients was 56 (range 18–70) y. Nineteen patients received therapy for acute myeloid leukaemia and 51 patients received autologous stem cell transplantation. At the onset and on days 1, 2, and 3 of each neutropenic fever episode, plasma lactate and serum C-reactive protein were determined. Criteria for severe sepsis were fulfilled in 13 neutropenic episodes. An elevated plasma lactate level was infrequent at the start of neutropenic fever (5%). There was no association of lactate level with the development of severe sepsis. Two patients died of septic shock, 1 patient with an exceptionally high and increasing level of lactate and the other patient with a normal lactate level. An elevated plasma lactate level at the start of neutropenic fever is not common and does not indicate severe sepsis, but high lactate and an impaired lactate decrease may signify a fatal course in neutropenic fever. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate etiology and consequences of neutropenic fever in AML patients. Two hundred and ninety neutropenic periods following chemotherapy in 84 AML patients were retrospectively evaluated. Neutropenic fever was found in 280 periods (97%). Severe sepsis developed in 35 occasions (13%) and 9 patients (11%) died due to severe sepsis. In 165 episodes with neutropenic fever (59%), the potential causative organism was found in blood cultures. Gram-negative bacteria were more commonly found in patients who developed severe sepsis (40% vs. 23%, p = 0.03). CRP after 2 - 3 days from start with fever was higher in patients with severe sepsis (190 mg/L vs. 96 mg/L, p < 0.001) but the rise in CRP rather coincided than preceded with the development of severe sepsis. Severe sepsis is associated with significant mortality in AML patients. Earlier methods than CRP are needed to predict development of severe sepsis. [ABSTRACT FROM AUTHOR]

Thirty adult lymphoma patients were studied prospectively with serial radionuclide ventriculography (RVG) and echocardiography (ECHO) to investigate whether changes in left ventricular (LV) diastolic function precede the impairment of LV systolic function during doxorubicin therapy. The patients received 8-10 cycles of CHOP to a cumulative doxorubicin dose of 400-500 mg/m². RVG and ECHO were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m². Left ventricular ejection fraction (LVEF) decreased from 58 ± 1.3 to 49.6 ± 1.7% (p < 0.001) and from 58 ± 1.7 to 52.5 ± 1.3% (p = 0.036) as assessed with RVG and 2D ECHO, respectively. Of the diastolic ECHO doppler indices peak E wave velocity decreased from 63.3 ± 3.2 to 51.3 ± 2.6 cm/s (p = 0.008) and LV filling during the first 1/3 of diastole (I/3FF) from 42.2 ± 1.7 to 36.5 ± 2.0% (p < 0.001 ). The decrease in LVEF was statistically significant after the cumulative doxorubicin dose of 200 mg/m² as assessed with RVG and after 400 mg/m² as assessed with 2D ECHO. The decrease in 1/3FF reached the statistical significance after the cumulative doxorubicin dose of 400 mg/m² and the decrease in peak E wave velocity after 500 mg/m[sup -2]. This study shows that during doxorubicin therapy there are significant changes both in systolic and diastolic LV function. In addition, these changes manifest at relatively low cumulative doxorubicin doses and occur concomitantly. Thus, the assessment of diastolic function provides no advantage over monitoring systolic function during doxorubicin therapy. [ABSTRACT FROM AUTHOR]

A 65-year old man with mixed connective tissue disease (MCTD) and severe therapy resistant polymyositis was considered for high-dose cyclophosphamide (200 mg/kg) supported by autologous stem cell transplantation (ASCT). During a 21 months follow-up there has been a significant subjective, but objectively only a slight improvement in muscle strength. Initially the levels of serum creatine kinase and serum aldolase normalised, but are at 21 months at about the same level as before ASCT. Based on histopathological examination there is still active myositis. Our case would suggests that this treatment may have some efficacy in MCTD with severe polymyositis although longer follow-up is needed. [ABSTRACT FROM AUTHOR]