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- Berlin, Gösta, 1944-, et al.
(author)
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Granulocyttransfusion bör övervägas vid neutropeni och allvarlig infektion [Granulocyte transfusion – when and how should it be used?]
- 2018
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In: Läkartidningen. - Stockholm, Sweden : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 115
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Research review (peer-reviewed)abstract
- There are no randomized controlled trials proving the clinical benefit of granulocyte transfusions. However, clinical experience and a number of case studies suggest that granulocyte transfusions may be life-saving in certain situations. In our opinion granulocyte transfusions should be considered for patients with profound neutropenia and severe, life-threatening infection not responding to antibiotic or antifungal therapy. Since the clinical effect seems to be dose-dependent, the granulocyte concentrate should contain a large number of cells, which usually means that the donor should be mobilized with steroids and G-CSF. Regular blood donors as well as relatives to the patient can be used for granulocyte donations with apheresis technique after information of the process. Granulocyte transfusion should be given daily as long as the indication remains. The clinical efficacy of the transfusions should be evaluated daily.
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- Cherif, Honar, et al.
(author)
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Adjuvanted influenza a (H1N1) 2009 vaccine in patients with hematological diseases : good safety and immunogenicity even in chemotherapy-treated patients
- 2013
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 90:5, s. 413-419
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Journal article (peer-reviewed)abstract
- Background Patients with hematological malignancies are more susceptible to viral infections including influenza. In 2009, the World Health Organization classified the novel influenza A (H1N1) virus as pandemic. The potential impact of this pandemic for patients with hematological disorders was unknown. Institutional guidelines recommended two doses of AS03-adjuvanted influenza A (H1N1) 2009 pandemic vaccine for these patients. Objectives We aimed to determine the safety, immunogenicity, and clinical efficacy of this vaccine in patients with hematological diseases. Furthermore, we compared the immunological responses to that obtained by the non-adjuvanted trivalent seasonal influenza vaccine (TIV). Methods All included patients received adjuvanted pandemic vaccine and the majority received TIV. Serum for antibody analyses was collected at five time points. Results Thirty-one patients with different hematological diseases were included. After the second vaccine dose, a total of 25 (81%) reached both protective levels of antibodies and seroconversion response. Antibody titers1:40 persisted for 50% of responding patients at 1yr. Seroconversion was observed in 69% of 14 patients who had undergone hematopoietic stem cell transplantation and in all (9/9) patients with myeloma (five with ongoing treatment including high-dose corticosteroids). After vaccination with TIV, seroconversions against the three included strains were detected in 28%, 40%, and 20%. Response to the adjuvanted pandemic vaccine was superior (P<0.009). Conclusions A substantial proportion of patients with hematological malignancies including patients undergoing chemotherapy mounted a good response to the adjuvanted pandemic vaccine. This vaccine had superior immunogenicity as compared to the non-adjuvanted TIV.
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- Cherif, Honar, et al.
(author)
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Clinical experience of granulocyte transfusion in the management of neutropenic patients with haematological malignancies and severe infection
- 2013
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:2, s. 112-116
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Journal article (peer-reviewed)abstract
- Background:Prolonged chemotherapy-induced neutropenia is a major risk factor for the development of severe bacterial and fungal infections. Infectious manifestations may progress despite adequate anti-infectious treatment and lead to a very high short-term mortality. Granulocyte transfusion (GT) therapy is often considered. However, its efficacy is not well documented.Methods:We retrospectively analyzed the clinical characteristics and outcome of a cohort of patients with haematological malignancies receiving GT during neutropenia and severe infection.Results:A total of 30 patients with a median age of 46 y (range 3-82 y) who had received 1 or more GT were included. Acute leukaemia (80%) and non-Hodgkin lymphoma (17%) predominated as the underlying malignancy. All patients had severe and prolonged (median 16 days) neutropenia. The major indications for GT were persistent fever and clinical deterioration despite broad anti-infectious therapy, in combination with progressive pneumonia (n = 16), neutropenic enterocolitis (n = 6), and soft tissue infections (n = 3). GTs were given for a median of 3 transfusions (range 1-14). The median time to fever defervescence after GT was 14 days (range 6-33 days). For 11 patients, the resolution of fever and all signs of infection could directly be related to GT, and 3 of these patients became long-term survivors. Mortality at 30 days post-GT was 40% and at 6 months post-GT was 72%. GT was well tolerated.Conclusions:A substantial proportion of severely ill neutropenic patients appeared to benefit from GT. The results further underline the need for well- designed, randomized, prospective trials to determine the efficacy of this intervention in patients with life-threatening infectious complications.
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- Cherif, Honar, et al.
(author)
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Combination treatment with an erythropoiesis-stimulating agent and intravenous iron alleviates anaemia in patients with hereditary haemorrhagic telangiectasia
- 2014
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 119:4, s. 350-353
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Journal article (peer-reviewed)abstract
- BackgroundPatients with hereditary haemorrhagic telangiectasia (HHT) suffer from recurrent epistaxis and bleeding from gastrointestinal telangiectasias that occur despite otherwise normal haemostasis and result in iron deficiency anaemia with increasing severity. In advanced disease, anaemia may be severe, be irresponsive to iron supplementation, and may lead to red blood cell transfusion dependency.MethodsWe conducted a retrospective study at our Centre for Osler's Disease to evaluate the effectiveness of adding an erythropoiesis-stimulating agent (ESA) to intravenous iron supplementation in the management of anaemic HHT patients. Blood values and treatment parameters were collected for nine months before combination therapy (iron supplementation only) and 12 months during combination therapy (iron supplementation plus ESA).ResultsFour patients received intravenous iron and an ESA with mean weekly doses of 126 mg and 17,300 units (U), respectively. Mean haemoglobin improved significantly during combination therapy, from 106 g/L to 119 g/L (p < 0.001).ConclusionAnaemia can be alleviated in patients with HHT who are irresponsive to intravenous iron supplementation, by addition of an ESA. The proposed mechanism behind the iron irresponsiveness is that the anaemia is caused by a combination of recurrent haemorrhage and anaemia of chronic disease.
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- Cherif, Honar
(author)
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Infections in patients with haematological malignancies
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Infectious complications are an important cause of morbidity and mortality in patients with hematological diseases, especially during chemotherapy induced neutropenia. This study was undertaken with the ultimate goal to improve the clinical management of infections in patients with hematological diseases. In a relatively large hematology centre where antibiotic prophylaxis was generally not used, the incidence of bacteremia and the spectrum of causative pathogens during the period 1988-2001, were determined. No tendency to a shift from gram-negative to gram-positive etiology was noted. Except for a significant increase in Enterococcus faecium bacteremia, the species distribution was essentially stable. The rates of antimicrobial resistance were low. The 7- and 30-day mortality rates were 6.3 and 15.6%, respectively. Species distribution and triazole susceptibility of colonising yeasts in neutropenic patients treated for hematological malignancies were prospectively analysed. Previous exposure to fluconazole prophylaxis was not associated with a shift from Candida albicans to non-albicans Candida species. However, fluconazole MICs were significantly higher in yeast isolates from patients who had received prophylaxis, indicating that azole prophylaxis may contribute to the emergence of less susceptible yeast strains. Cefepime monotherapy was, in a prospective randomised study, found to be as safe and as effective as imipenem-cilastatin in the management of febrile neutropenia in patients treated for hematological malignancies. In patients with neutropenia and fever of unknown origin (FUO), the early discontinuation of all antibiotic therapy 48 hours after fever defervescence was not associated with an increased rate of fever relapse or mortality. This therapeutic approach seems promising in patients with FUO. Prospective large randomised trials are warranted. The Multinational Association of Supportive Care in Cancer (MASCC) risk-index score was validated in patients with hematological malignancies. The risk-index identified patients with febrile neutropenia who were at low risk for the development of serious medical complication with a specificity, sensitivity and positive predictive value of 87%, 58% and 84%, respectively. Accordingly, this risk-index was found to be a valuable tool for the identification of low-risk patients. A substantial proportion (36%) of low-risk patients with febrile neutropenia were ineligible for oral antibiotic therapy; while the remaining 64% received oral antibiotic treatment following discharge from the hospital 24 hours after fever defervescence. Upon final evaluation 95% remained afebrile and there was no early mortality in this group. The strategy of early hospital discharge with oral antibiotic therapy of carefully selected low-risk patients offered a feasible, safe and costeffective alternative to the conventional management of these patients. Splenectomy is associated with increased risk to pneumococcal infections. Antibody response to vaccination with 23-valent pneumococcal polysaccharide vaccine in splenectomised patients with hematological disorders was determined. A substantial proportion (28%) of these patients had a poor antibody response to vaccination. During the long follow-up period (median observation time 7.5 years) all recorded episodes of pneumococcal infections were confined to poor responders. Patients who had a poor response to vaccination did not benefit from revaccination. With the possible exception of age, no other clinical characteristics could predict a poor antibody response. Poor responders should be offered other prophylactic measures.
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- Cherif, Honar, et al.
(author)
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Patient was wrongly diagnosed and repeatedly treated for immune thrombocytopenia for 50 years
- 2018
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 115
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Journal article (peer-reviewed)abstract
- We report on a patient with inherited macrothrombocytopenia, MYH9 related disease (MYH9-RD). The patient was wrongly diagnosed and repeatedly treated for immune thrombocytopenia (ITP) for nearly 50 years. Cases of misdiagnosed MYH9-RD and other hereditary thrombocytopenias have been described previously. Typical clinical features such as renal failure and/or progressive loss of hearing should give grounds to suspect hereditary thrombocytopenia. Initial laboratory diagnosis can start with a simple blood smear followed by immunohistochemistry and genotyping. Therapy with thrombopoietin receptor agonists may be beneficial in selected cases of MYH9-RD. ITP treatments including splenectomy are not indicated and may cause harm.
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- Dickinson, Michael, et al.
(author)
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Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia
- 2018
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 132:25, s. 2629-2638
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Journal article (peer-reviewed)abstract
- Azacitidine treatment of myelodysplastic syndromes (MDSs) generally exacerbates thrombocytopenia during the first treatment cycles. A Study of Eltrombopag in Myelodysplastic Syndromes Receiving Azacitidine (SUPPORT), a phase 3, randomized, double-blind, placebo-controlled study, investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. International Prognostic Scoring System intermediate-1, intermediate-2, or high-risk MDS patients with baseline platelets <75 3 10(9)/L were randomized 1: 1 to eltrombopag (start, 200 mg/d [East Asians, 100 mg/d], maximum, 300 mg/d [East Asians, 150 mg/d]) or placebo, plus azacitidine (75 mg/m2 subcutaneously once daily for 7 days every 28 days). The primary end point was the proportion of patients platelet transfusion-free during cycles 1 through 4 of azacitidine therapy. Based on planned interim analyses, an independent data monitoring committee recommended stopping the study prematurely because efficacy outcomes crossed the predefined futility threshold and for safety reasons. At termination, 28/179 (16%) eltrombopag and 55/177 (31%) placebo patients met the primary end point. Overall response (International Working Group criteria; complete, marrow, or partial response) occurred in 20% and 35% of eltrombopag and placebo patients, respectively, by investigator assessment. There was no difference in hematologic improvement in any cell lineage between the 2 arms. There was no improvement in overall or progression-free survival. Adverse events with >= 10% occurrence in the eltrombopag vs placebo arm were febrile neutropenia and diarrhea. Compared with azacitidine alone, eltrombopag plus azacitidine worsened platelet recovery, with lower response rates and a trend toward increased progression to acute myeloid leukemia. This trial was registered at www.clinicaltrials.govas# NCT02158936.
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