| 1. |
- Ahlstrand, Erik, 1974-, et al.
(författare)
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Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy
- 2012
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - New York, USA : Springer. - 0934-9723 .- 1435-4373. ; 31:7, s. 1679-1687
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to prospectively describe the colonization pattern of coagulase-negative staphylococci (CoNS) and the relationship between colonizing and invasive CoNS isolates among patients undergoing treatment for hematological malignancy. Fourteen newly diagnosed patients were included with either multiple myeloma or acute leukemia. Patients were repeatedly sampled from nares, throat, axillae, and perineum, and the CoNS isolates obtained were phenotypically characterized together with blood isolates of CoNS using the PhenePlate system (PhP). During the treatment a gradual reduction in the heterogeneity of colonizing CoNS was observed as well as an inter-patient accumulation of phenotypically related and multi-drug-resistant CoNS. These clusters of CoNS persisted for 2–3 months after the end of therapy. Ten positive blood cultures of CoNS were obtained and in the majority of these cases CoNS of the same PhP type were found in superficial cultures collected prior to the blood culture sampling. In conclusion, the study shows that therapy for hematological malignancy is associated with a homogenization of colonizing CoNS isolates and that this acquired flora of CoNS is persistent several months after the end of therapy. Furthermore, the results suggest that the source of bloodstream infections of CoNS in hematological patients is colonizing CoNS of the skin and mucosa.
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| 2. |
- Ahlstrand, Erik, 1974-, et al.
(författare)
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Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies
- 2014
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 122:6, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.
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| 3. |
- Deneberg, Stefan, et al.
(författare)
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Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:20, s. 5573-5582
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetically normal acute myeloid leukemia (CN-AML) comprise between forty and fifty percent of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group molecular aberrations such as FLT3ITD, NPM1 and CEBPA mutations recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer including AML. We investigated in total 118 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them to normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (p=0.0004 and 0.04, respectively). Genome-wide methylation levels were elevated in IDH mutated samples (p=0.006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (p<0.0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression free (OR 0.47, p=0.01) and overall survival (OR 0.36, p=0.001). In summary, genome wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.
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| 4. |
- Fergedal, May, et al.
(författare)
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Differences in CD14 and alpha-naphthyl acetate esterase positivity and relation to prognosis in AML
- 1998
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Ingår i: Leukemia research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 22:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-naphthyl acetate esterase (ANAE) and CD14 expression, used for determination of monocytic cells, were compared and related to prognosis in 65 AML patients. Bone marrow aspiration material from AML patients has been used for the cytochemistry as well as flow cytometry. All non-erythroid cells have been included in the evaluation in both methods. 17/65 cases showed at least 15% difference between the proportion CD14 and ANAE positive cells. Cases with 20% or more CD14 positivity had poorer prognosis. For FAB classes M0-M3, presence of 10% or more CD14 was negative for overall survival (P = 0.01). ANAE did not show significant prognostic influence.
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| 5. |
- Jonsson, Thomas B., 1971-, et al.
(författare)
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Adverse events during treatment limb ischemia with autologous peripheral blood mononuclear cell implant
- 2012
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Ingår i: International Journal of Angiology. - Turin, Italy : Edizioni Minerva Medica. - 0392-9590 .- 1827-1839. ; 31:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work.Methods: We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks.Results: Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.Conclusion: Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.
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| 6. |
- Lehmann, S, et al.
(författare)
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Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry.
- 2011
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 25:7, s. 1128-34
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100,000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.
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| 7. |
- Lehmann, S, et al.
(författare)
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Targeting p53 in vivo : a first-in-man study with the p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer
- 2012
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:29, s. 3633-3639
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246.PATIENTS AND METHODS: APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg.RESULTS: MTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response.CONCLUSION: We conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo.
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| 8. |
- Persson, Lennart, et al.
(författare)
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Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia
- 2005
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 74:4, s. 297-303
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we evaluated the predictive values of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) for determining the clinical course in febrile neutropenic patients. Daily plasma analyses during the fever course were performed in 101 episodes with fever and chemotherapy-induced neutropenia (neutrophil count <0.5 x 10(9)/L). Procalcitonin (PCT) and IL-6 values were significantly higher in febrile episodes in patients who developed complications. Procalcitonin with a cut-off value of < or =0.4 ng/mL or IL-6 < or =50 pg/mL 3 d after fever onset indicated daily high negative predictive values (NPVs) (91-100%) for episodes with complications. No marker could predict deterioration; however, daily low plasma concentrations of PCT or IL-6 during the first 8 d of fever were found to be a good predictor of no subsequent complications in neutropenic patients and therefore to be a helpful tool for limiting anti-microbial therapy.
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| 9. |
- Prenkert, Malin, 1967-, et al.
(författare)
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CRIM1 is expressed at higher levels in drug-resistant than in drug-sensitive myeloid leukemia HL60 cells
- 2010
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Ingår i: Anticancer Research. - Athens, Greece : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:10, s. 4157-61
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study was to explore possible differences in the mRNA expression levels of CRIM1, SMAD5, BMP4 and BMP7 in sensitive (S) and multidrug-resistant (R0.5) myeloid leukemia HL60 cells.Materials and Methods: HL60S and HL60R0.5 cells were exposed to daunorubicin (DNR) or cytarabine (Ara-C).Results: Baseline levels of CRIM1 were found to be 15-fold higher in HL60R0.5 than in HL60S. Sixteen hours of exposure to DNR resulted in a 5.6-fold increase in CRIM1 levels in HL60S. Exposure to either DNR or Ara-C resulted in modest increases in CRIM1 levels in HL60R0.5. Similarly, baseline levels of SMAD5 and BMP4 were higher in HL60R0.5 than in HL60S cells. Analysis of the drug SMAD5-resistance marker permeability-glycoprotein (Pgp) revealed that CRIM1 and Pgp exhibit a covariance pattern of expression.Conclusion: This study demonstrated that CRIM1 is expressed at high levels in resistant leukemia cells, indicating that CRIM1 may play a role in drug-resistance.
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| 10. |
- Uggla, Bertil, 1962-, et al.
(författare)
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Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells
- 2001
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Ingår i: Leukemia research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 25:11, s. 961-966
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerase IIalpha (topoII alpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.
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