Infections during induction therapy of childhood acute lymphoblastic leukemia--no association to mannose-binding lectin deficiency

OBJECTIVES: Infection during the induction phase of childhood acute lymphoblastic leukemia (ALL) is a major cause of morbidity and mortality. Several studies have indicated that genetically determined low serum levels of mannose-binding lectin (MBL), a component of innate immunity, are associated with increased risk for infections in patients receiving chemotherapy. Thus, these patients have been proposed to be candidates for MBL replacement therapy. METHODS: In a population-based cohort of 137 children with ALL treated at a single pediatric hematology-oncology center with an almost identical chemotherapy regimen, we studied the relationship between polymorphisms in the MBL gene (MBL2) and the MBL2 promoter and the risk of infections during the first 50 d of induction therapy. RESULTS: No increased frequency of infection was seen for the children with genotypes encoding serum low levels of MBL. A higher incidence of fever (P < 0.004), infectious events (P = 0.025), days with neutropenia (P < 0.001) and a higher frequency of antimicrobial therapy (P = 0.0007) were seen in the young age group (<2.5 yr) compared with the older age group (> or =2.5 yr), independent of the MBL genotype. CONCLUSIONS: MBL deficiency did not influence the frequency of infections in children receiving induction chemotherapy for ALL, not even in the youngest children (<2.5 yr) whom we found to have the highest risk for infections.     

Mannan-Binding Lectin Levels Related to Spontaneous Abortion in Brazilian Patients with Celiac Disease

Low concentration of mannan-binding lectin (MBL) has been related to unexplained spontaneous abortion (SA), which has also been observed in an increased frequency in patients with celiac disease (CD). In this study, plasma levels of MBL were determined in patients with CD and irritable bowel syndrome (IBS) in order to investigate whether there is an association of MBL levels and the occurrence of SA in these patients. MBL concentration was determined in 46 patients with CD (28 without and 18 with report of SA) and 38 patients with IBS (25 without and 13 with report of SA). A higher frequency of SA was observed in women with CD when compared to IBS patients (23.2 vs. 13.9%; P = 0.046). No significant difference was observed in MBL concentrations between patients with CD, IBS, and healthy controls, nor between patients with or without occurrence of SA. These results suggest that the serum levels of MBL and the occurrence of SA in women with CD and IBS are not causally related.     

Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia]

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.     

Serum mannose-binding lectin levels are decreased in behcet's disease and associated with disease severity

OBJECTIVE: To investigate serum levels of mannose-binding lectin (MBL), a complement-like protein of collectin family, in patients with Behcet's disease (BD). METHODS: MBL levels were measured in sera of 130 patients with BD, 64 patients with recurrent oral ulcerations (ROU), and 105 healthy controls (HC) with ELISA. RESULTS: Patients with BD had significantly lower median serum MBL levels compared to HC (1857 vs 3136 ng/ml, p = 0.001). No significant difference was observed in median serum MBL levels between BD and ROU (2309 ng/ml, p = 0.252). Low MBL levels (/= 4) was more frequently observed in BD patients with very low serum MBL levels (相似文献   

Sepsis in acute myeloid leukaemia patients receiving high‐dose chemotherapy: No impact of chitotriosidase and mannose‐binding lectin polymorphisms

Infections after chemotherapy often cause significant morbidity in patients with acute myeloid leukaemia (AML). Chitotriosidase (CHIT) and mannose‐binding lectin (MBL) are part of the innate immune system. Polymorphism in the CHIT‐coding gene (CHIT1) may be associated with Gram‐negative sepsis in children with AML, and polymorphism in the MBL‐coding gene (MBL2) seems to modify the risk of infections in several patient groups. The purpose of this study was to investigate the possible associations between polymorphisms in CHIT1, MBL2 and sepsis in adult patients treated with high‐dose chemotherapy for AML. We included 190 patients treated with 526 cycles of chemotherapy. The follow‐up period was 6 months from the diagnosis of AML. Prophylactic antibiotics were not used. We identified 604 febrile episodes with 246 episodes of sepsis. Thirty‐two patients (17%) either died from infection or infection was a major concomitant factor for death. No significant associations between CHIT1 polymorphism and sepsis (P = 0.85) or death caused by sepsis (P = 0.14) were found. Furthermore, no significant associations between MBL2 polymorphism and sepsis (P = 0.76) or death caused by sepsis (P = 0.24) were observed. The severe and long‐lasting neutropenia and mucositis after chemotherapy may explain why the MBL system does not protect against sepsis in patients with AML. Replacement therapy with recombinant MBL is not likely to decrease the risk of sepsis in patients with AML.     

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum during induction treatment of acute leukaemia

Granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are increasingly used to stimulate granulopoiesis in neutropenic patients but in most cases without any knowledge of the endogenous CSF-levels. With the purpose to define serum levels of GM-CSF and G-CSF during induction chemotherapy and haematological reconstitution in patients with acute leukaemia we have used enzyme-linked immunosorbent assay (ELISA) techniques to measure these growth factors in 18 patients with acute myeloid leukaemia (AML) and eight patients with acute lymphoblastic or undifferentiated leukaemia (ALL/AUL). G-CSF above 0.05 ng/ml was detected in 54% of the analysed AML samples, median 0.29 (range 0.05-2.80) ng/ml; and in 40% of analysed ALL/AUL samples, median 0.09 (range 0.05-3.00) ng/ml. In patients with AML there was a clear correlation between an elevated serum concentration of G-CSF and documented infections. On the other hand, 15/18 of the patients with acute myeloid leukaemia and 8/8 patients with ALL/AUL had non-detectable levels of GM-CSF (less than 0.10 ng/ml). Two patients had measurable levels of GM-CSF in all samples, median 0.71 (range 0.26-1.18) ng/ml and in these patients the levels successively decreased during and after chemotherapy and did not increase in response to infections. In normals detectable levels of GM-CSF were found in 2/35 individuals and G-CSF in 0/10 individuals.     

Serum levels of endothelium-derived endocan are increased in patients with untreated acute myeloid leukemia

Endocan is a soluble proteoglycan expressed only by vascular endothelium and is also found circulating in the bloodstream. Inflammatory cytokines as well as proangiogenic growth factors increase its expression, and increased serum levels are found in immunocompetent patients with sepsis. We investigated serum endocan levels in patients with untreated acute myeloid leukemia (AML) and AML patients during chemotherapy-induced bone marrow failure. We observed increased levels in 40 AML patients compared with healthy controls, which was also confirmed in a second cohort. The serum levels decreased after intensive chemotherapy and subsequent severe chemotherapy-induced cytopenia, and increased levels were thereafter observed during bone marrow regeneration. However, even for these severely immunocompromized patients, serum endocan levels increased during complicating bacterial infections before a decrease was seen during antibiotic therapy. To conclude, serum endocan is a disease marker in AML, but serum levels are also affected by complicating infections and bone marrow regeneration.     

GH strongly affects serum concentrations of mannan-binding lectin: evidence for a new IGF-I independent immunomodulatory effect of GH.

Studies in animals and humans indicate that GH and IGF-I modulate immune function. Recently, it was reported that GH therapy increased the mortality in critically ill patients. The excessive mortality was almost entirely attributable to septic shock or multiorgan failure, suggesting that a GH-induced modulation of immune function was involved. In the present study, we examined whether GH or IGF-I influences the serum concentrations of mannan-binding lectin (MBL). MBL is a plasma protein of the innate immune system that initiates the complement cascade and activates inflammation after binding to carbohydrate structures on microbial surfaces. We performed a cross-over study of 16 healthy men examined during a control period, and during treatment with either GH or IGF-I for 6 d. The levels of MBL were more than doubled during GH treatment, whereas no changes were observed in the IGF-I group or during the control period (P < 0.001). IGF-I levels were elevated similarly during treatment with GH and IGF-I. Subsequently, we studied 30 healthy persons and 25 GH-deficient (GHD) patients randomized to treatment with GH or placebo in a double-blinded manner, and further included samples from 23 patients with active acromegaly examined before and after treatment with octreotide or the GH-receptor antagonist pegvisomant for 3 months. Baseline concentrations of MBL were lower in GHD patients and higher in acromegalic patients than in healthy subjects (P < 0.02). Treatment with GH doubled the MBL concentrations in healthy subjects and almost quadrupled the concentrations in GHD patients; whereas in acromegalic patients, the levels of MBL were reduced to approximately two thirds of the initial values during treatment with octreotide or pegvisomant. Our results demonstrate that treatment with GH, but not IGF-I, significantly increases MBL concentrations. The clinical consequences of this new link between the endocrine and the immune system remain to be elucidated.     

Association of mannose binding lectin (MBL) gene polymorphism and serum MBL concentration with characteristics and progression of systemic lupus erythematosus

OBJECTIVE: To determine whether occurrence, characteristics, and progression of systemic lupus erythematosus (SLE) are associated with polymorphism of the mannose binding lectin (MBL) gene and with serum MBL concentration. METHODS: Codon 54 MBL gene polymorphism of 147 patients with SLE and 160 healthy controls was determined by polymerase chain reaction-restriction fragment length polymorphism. Serum concentration of MBL was measured by enzyme immunoassay. Fluctuations of serum MBL were analysed with respect to disease characteristics and activity. RESULTS: Frequency of homozygosity for codon 54 minority allele was 6% (9/147) in patients with SLE, and significantly higher than in controls (p = 0.0294, Fisher's exact test). MBL polymorphism in patients with SLE was not significantly associated with disease characteristics or immunological phenotypes. Patients homozygous for the B allele tended to have a higher risk of infection during treatment. Levels of C3 and CH(50) were slightly, but significantly, associated with serum MBL concentration in patients with SLE homozygous for the majority allele. During the course of SLE, serum MBL concentration increased in 6/14 patients, and decreased in 7 after initiation of immunosuppressive treatment. CONCLUSIONS: MBL gene polymorphism influences susceptibility to SLE, but has no direct effect on disease characteristics. Serum MBL levels fluctuate during the course of SLE in individual patients. MBL genotyping may be useful in assessing the risk of infection during treatment of SLE.     

Mannose-binding lectin and susceptibility to infection in Chinese patients with systemic lupus erythematosus

OBJECTIVE: To test the hypothesis that low serum mannose-binding lectin (MBL) levels, as a result of the single-nucleotide polymorphisms in the promoter region (-221 X/Y) and exon 1 (codon 54 A/B) of the MBL2 gene, predispose to infection in Chinese patients with systemic lupus erythematosus (SLE). METHODS: Two hundred forty-five patients with SLE were prospectively followed for the development of major infective episodes that required hospitalization and antibiotic treatment during 1992-2005. MBL genotypes were determined by polymerase chain reaction and serum MBL levels were measured by ELISA. RESULTS: In total, 254 major infections developed in 130 patients. Serum MBL levels were shown to correlate inversely with the number of bacterial infections (r = -0.13, p = 0.03). The distribution of MBL genotypes was similar in patients with and without major infection (p = 0.84). Patients with major infection also had more major lupus exacerbations that required daily prednisolone dose > or = 15 mg. Logistic regression showed that log MBL level (odds ratio 0.516, 95% confidence interval 0.305-0.873; p = 0.01) and major lupus exacerbation (OR 1.382, 95% CI 1.154-1.654; p < 0.001) were independent risk factors to major bacterial infection after adjustment for age and disease duration. Multiple regression analysis showed an increase in risk of bacterial infection by 34.2% for every decrease in serum MBL level by one log, and by 22.8% for each increase in number of major lupus exacerbations. CONCLUSION: Low serum MBL level predisposes Chinese patients with SLE to more major infections, in particular bacterial ones.     

Serum concentration of complement components of the lectin pathway in maintenance hemodialysis patients, and relatively higher levels of L-Ficolin and MASP-2 in Mannose-binding lectin deficiency

Mannose-binding lectin (MBL), L-ficolin and MBL associated serine protease-2 (MASP-2) are molecules involved in initiation of the lectin pathway (LP) in the complement system. Although MBL deficiency is observed in almost 10% of healthy people, studies of associations between MBL deficiency and end-stage renal disease (ESRD) remain rare. The objective of the present study is to clarify the significance of the LP in maintenance hemodialysis (HD) patients, especially in terms of MBL levels. Two hundred and forty-four HD patients who had been followed up for 74±84months and 199 healthy controls were included in this study. Measurements of serum concentrations of MBL, L-ficolin, and MASP-2 were performed. Low serum MBL levels (<0.1μg/mL) in the patients were confirmed by examination of a point mutation in the Mbl-2 gene. Seventeen HD patients (7%) and 20 healthy controls (10%) had MBL deficiency. During the follow-up period, 99 patients died. There was no significant difference in the frequency of deaths by infectious diseases between MBL deficient and non-deficient patients. In both patients and healthy controls with MBL deficiency, the serum concentration of L-ficolin tended to be high, and that of MASP-2 was significantly high (P<0.05). MBL deficiency is not a risk factor for HD induction or life-threatening infections. It is postulated that the elevation of concentration of the two components of the LP, L-ficolin and MASP-2, may compensate for the insufficient activity of the LP in MBL deficiency.     

Impact of mannose-binding lectin deficiency on radiocontrast-induced renal dysfunction: a post-hoc analysis of a multicenter randomized controlled trial

ABSTRACT: BACKGROUND: Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort. METHODS: 246 patients with advanced non--dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of >=0.5 mg/dL or >=25 % within 48 hours) or cystatin C-based (increase of >=10 % within 24 hours) CIN. RESULTS: The incidence of creatinine-based and cystatin C-based CIN was 6.5 % and 24 %, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of >=10 % showed significantly higher MBL levels than patients with a rise of <10 % (median 2885 (IQR 1193--4471) vs. 1997 (IQR 439--3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels<=500 ng/ml) was identified as an inverse predictor of a cystatin C increase >=10 % (OR 0.34, 95 % CI 0.15-0.8, p = 0.01). CONCLUSION: MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.     

Bone Marrow MicroRNA-335 Level Predicts the Chemotherapy Response and Prognosis of Adult Acute Myeloid Leukemia

The aim of this study was to investigate the role of microRNA-335 (miR-335) in determining the treatment response and prognosis in adult acute myeloid leukemia (AML) patients receiving the cytarabine (Ara-C)-based chemotherapy.A total of 204 adult AML patients were collected. The miR-335 levels in serum and bone marrow samples from these patients were determined. All patients received Ara-C-based standard induction chemotherapy regimens. The treatment response to Ara-C-based chemotherapy was evaluated. All patients were followed for prognostic analyses.The levels of miR-335 in bone marrow and serum samples from adult AML patients achieving complete response were significantly higher than those without. The serum miR-335 level was not associated with the chemotherapy response and prognosis in these AML patients. In contrast, high bone marrow miR-335 level was significantly associated with a poor treatment response and also predicted a worse prognosis indicated by the relapse-free survival and overall survival periods in adult AML patients receiving Ara-C-based chemotherapy.Our finding suggests that bone marrow miR-335 level may be used as a marker to predict the chemotherapy response and prognosis in adult AML patients.     

Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels

Adverse outcome of critical illness is often caused by systemic inflammation and sepsis. A recent study showed that mortality is significantly reduced by maintenance of normoglycemia using intensive insulin therapy. We examined whether the beneficial effects of intensive insulin therapy involve modulations of mannose-binding lectin (MBL) and C-reactive protein (CRP) levels. From a study of 1548 patients randomly assigned to either conventional treatment or intensive insulin therapy at an intensive care unit (ICU) we included all 451 patients who needed prolonged intensive care (>5 d). CRP and MBL concentrations were measured on admission, d 5, d 15, and the last day in the ICU. In all patients, serum MBL concentrations increased with time in the ICU (P < 0.0001). This acute phase response was suppressed by intensive insulin therapy at all time points studied (P < 0.02). Selectively in patients receiving conventional therapy, MBL concentrations at baseline were almost 3 times higher in survivors than in nonsurvivors (P = 0.04). Baseline CRP concentrations were elevated, but decreased with time in ICU (P < 0.0001). The decrease in CRP was significantly more pronounced in the intensive insulin-treated patients compared with the conventionally treated patients (P 相似文献   

Protein C and S levels in acute leukemia.

Patients with acute leukemia undergoing remission induction chemotherapy occasionally develop venous thrombosis despite severe thrombocytopenia and in the absence of disseminated intravascular coagulation. This observation prompted us to study the levels of the naturally occurring anticoagulant proteins C and S prospectively in patients undergoing remission induction chemotherapy for acute leukemia. Plasma samples from 50 adult patients with acute leukemia (34 AML, 16 ALL) were analyzed for protein C antigen, functional protein C, immunologic total and free protein S as well as levels of C4b binding protein (C4bBP). Plasma levels of immunologic protein C were significantly lower in patients with active acute myelocytic leukemia (mean = 77.9) than in controls (mean = 123.6) or patients in remission (mean = 132). Functional protein C levels were also significantly lower in AML patients with active disease (mean = 58.5) than controls (mean = 95.5) or patients in remission (mean = 98.5). Patients with acute lymphocytic leukemia (ALL) had normal levels of immunologic and functional protein C. Although total protein S levels were normal in all patients studied, levels of free protein S were significantly decreased in patients with active AML (mean = 29.3) compared with patients in remission (mean = 42.0) or controls (mean = 42.4). In contrast, patients with ALL, both with active disease and in remission had normal free protein S levels. This decrease in free protein S seen in active AML was not associated with liver disease, white cell count or an increase in C4bBP. These findings provide a possible explanation for the occasional occurrence of venous thrombosis in patients with acute myelocytic leukemia.     

The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome

OBJECTIVE: Studies in animals and humans indicate that growth hormone (GH) and insulin-like growth factor-I (IGF-I) modulate immune function. Recently, it was reported that GH therapy increased the level of mannan-binding lectin (MBL) in normal patients, and that treatment of acromegalics with pegvisomant decreased the levels of MBL. The effect on MBL was thought to be due to a specific action of GH, since IGF-I treatment did not affect MBL. Whether it is advantageous or not to have high or low levels of MBL is not known. Likewise, it is not clear how the modifications induced by GH affect immune function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). DESIGN: Study 1: a double-blind crossover study of 12 healthy TS adolescents examined during treatment with either placebo or GH for 2 months, and compared with a control group. Study 2: triple-blind crossover study of 9 healthy TS adolescents randomized to treatment with placebo, GH or GH+17beta-estradiol. Study 3: 60 adult TS patients (55 received HRT) compared with 59 age-matched controls. Study 4: 27 patients with TS were examined before and during sex hormone replacement with 17beta-estradiol and norethisterone and compared with age-matched controls (n=24). METHODS: Measurement of MBL, SP-D, DBP, and other inflammation markers. RESULTS: Study 1: the levels of MBL (P=0.002) and SP-D (P=0.012) increased during GH treatment, whereas no changes were observed in comparison with controls. DBP was unchanged by GH, but was significantly higher in TS compared with controls (P=0.017). Study 2: treatment with GH increased MBL (P=0.045) and SP-D (P=0.05) concentrations in TS, while treatment with GH+17beta-estradiol did not increase levels further. DBP was unchanged by treatment. Study 3: levels of MBL, SP-D, and DBP were similar in adult TS and control subjects. Study 4: DBP levels decreased in response to HRT, while MBL and SPD levels were unchanged. Levels of all three plasma proteins were similar to controls. CONCLUSION: We show that treatment with GH significantly increases MBL and SP-D concentrations in TS, while HRT marginally decreases DBP. Whether the present findings, suggesting a link between the endocrine and the immune system, have clinical consequences needs to be studied further.     

Leptin in human acute myelogenous leukemia: studies of in vivo levels and in vitro effects on native functional leukemia blasts

BACKGROUND AND OBJECTIVES: Leptin receptors can be expressed by acute myelogenous leukemia (AML) cells, but the functional effects of leptin on native AML blasts have not been characterized in detail. We investigated systemic leptin levels in AML patients and in vitro effects of leptin on cultured AML blasts. DESIGN AND METHODS: Serum leptin levels were compared for patients with untreated AML and healthy controls. Native AML blasts were derived from a large group of consecutive patients, and effects of leptin on proliferation (suspension cultures and colony formation), constitutive cytokine secretion, differentiation and apoptosis regulation were assayed in vitro. RESULTS: Systemic leptin levels were decreased in patients with untreated AML, and leptin levels in acute leukemia patients were not altered during severe chemotherapy-induced cytopenia and complicating febrile neutropenia. In vitro studies demonstrated that leptin increased AML blast release of interleukin (IL) 1beta, IL6, tumor necrosis factor (TNF) alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF). This enhancing effect showed no correlation with CD34 expression and was not dependent on the presence of serum, induction of differentiation or alteration of caspase 3 activity with decreased in vitro apoptosis. Leptin also increased spontaneous AML blast proliferation, whereas divergent effects on blast proliferation were observed in the presence of exogenous cytokines. The in vitro effects were usually observed at concentrations exceeding the systemic levels. INTERPRETATION AND CONCLUSIONS: Our results suggest that systemic leptin levels alone do not have a major influence on native AML blasts, but the systemic levels in combination with local leptin release in the bone marrow may affect the functional characteristics of these cells.     

The significance of lysozyme estimations in acute myeloid and chronic monocytic leukaemia

Summary . Serum and urine concentrations of lysozyme (muramidase) were estimated by a turbidimetric method in 17 adults suffering from acute myeloid leukaemia (AML) and six from chronic monocytic leukaemia (CMoL). AML case were classified on cytological and cytochemical criteria as myeloblastic (AMbL), myelomonocytic (AMML) or monoblastic-monocytic (AMoL) leukaemia. Serum lysozyme was within normal limits in AMbL, was increased from moderate to high levels in AMML and greatly increaed in all but one AMoL; CMoL had also raised concentrations. The concentrations of lysozyme in 24 hr collections of urine corresponded in general with the serum levels. When serum levels were very high (above 400 μg/ml) the ratio urine/serum was raised 15–40 times. Repeated lysozyme estimations made for periods of 1–12 mth during the course of treatment in seven patients with AMML or AMoL demonstrated three patterns of changes: (a) in four cases the serum concentrations fell during remission and rose again during relapse; when the remission was not complete they remained above the upper limit of the normal range; (b) in one case the changes were as (a), but when the relapse occurred the serum and urine concentrations remained normal; (c) in two cases of AMML with only moderately increased lysozyme levels, the changes in the serum concentration followed only the changes in the monocyte counts, thus reflecting only partially the activity of the disease. Lysozyme estimations are useful in classifying AML and in assessing the degree of remission achieved as a result of treatment. Additional observations regarding the presence of abnormalities in the neutrophils, lymphadenopathy, and gum hypertrophy were also found to be useful in the classification of AML, the former being more common in AMbL and the latter in AMoL.     

Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases

Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non‐conventional drugs such as fludarabine are considered responsible for the increased risk of infections. Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients ≤65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02). Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram‐negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram‐negative, Gram‐positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram‐negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram‐negative, Gram‐positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation. Conclusions: These data, although retrospectively collected, suggest that fludarabine‐based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.     

Mannose binding lectin and soluble Toll-like receptor 2 in heart failure following acute myocardial infarction

BackgroundTo determine the relationship between markers of innate immunity and clinical outcomes in patients with heart failure (HF) after acute myocardial infarction (AMI). Atherogenesis and HF is associated with the altered control of inflammation by innate immune defenses that include pattern-recognition molecules such as Toll-like receptors (TLRs) and mannose-binding lectin (MBL).Methods and ResultsWe assessed circulating levels, and relationships with adverse outcomes of MBL and sTLR2 levels in 234 patients with AMI complicated with HF. Blood was sampled at baseline (median 3 days after AMI), 1 month, 1 year, and 2 years. For comparison, we also measured MBL and sTLR2 levels in 20 age- and sex-matched healthy controls. Patients with post-MI HF had markedly decreased serum levels of sTLR2 at baseline that increased during follow-up, but did not reach the concentrations present in healthy controls. In contrast, serum MBL levels were initially normal in patients with post-MI HF, but decreased during follow-up, and MBL levels measured 1 month after the index infarct were inversely associated with a higher incidence of reinfarction.ConclusionThese findings suggest that circulating levels of MBL and sTLR2 may reflect different aspects of the innate immune response and further suggest the involvement of innate immunity responses in the pathogenesis of post-MI HF.