373 results
Search Results
2. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper.
- Author
-
Hughes, Daniel, Yong, Kwee, Ramasamy, Karthik, Stern, Simon, Boyle, Eileen, Ashcroft, John, Basheer, Faisal, Rabin, Neil, and Pratt, Guy
- Subjects
- *
MONOCLONAL gammopathies , *MULTIPLE myeloma , *HEMATOLOGY , *DIAGNOSIS , *BRAIN natriuretic factor , *PLASMA cell diseases - Abstract
This article provides information on the diagnosis and management of smouldering myeloma, a precursor condition to multiple myeloma. It discusses various diagnostic tests and imaging techniques used to identify smouldering myeloma and emphasizes the importance of restaging if there is evidence of progression. The article also provides recommendations for screening and initial investigations for suspected myeloma. Additionally, it discusses risk stratification models and treatment options for smouldering myeloma, including the use of lenalidomide. The article concludes by highlighting ongoing clinical trials and the need for further research in the treatment of smouldering myeloma. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
3. Investigation and management of the monoclonal gammopathy of undetermined significance: A British Society for Haematology Good Practice Paper.
- Author
-
Stern, Simon, Chaudhuri, Satarupa, Drayson, Mark, Henshaw, Sarah, Karunanithi, Kamaraj, and Willis, Fenella
- Subjects
- *
BEST practices , *HEMATOLOGY , *MEDICAL screening - Abstract
Summary: This Good Practice Paper provides recommendations for the diagnosis, risk stratification and management of the monoclonal gammopathy of undetermined significance (MGUS). It describes the recently recognised entity of the monoclonal gammopathy of clinical significance (MGCS), and recommends how it should be managed. The potential for targeted population screening for MGUS is also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. Management of older patients with frailty and acute myeloid leukaemia: A British Society for Haematology good practice paper.
- Author
-
Dennis, Mike, Copland, Mhairi, Kaur, Harpreet, Kell, Jonathan, Nikolousis, Emmanouil, Mehta, Priyanka, Palanicawandar, Renuka, Potter, Victoria, Raj, Kavita, Thomas, Ian, and Wilson, Andrew
- Subjects
- *
ACUTE myeloid leukemia , *OLDER patients , *FEBRILE neutropenia , *MUCOSITIS , *MEDICAL personnel , *ACUTE promyelocytic leukemia , *HEMATOLOGY - Abstract
EVALUATION OF ABILITY TO TOLERATE THERAPY (COMORBIDITY ASSESSMENT AND MORTALITY PREDICTION) Evaluation of fitness for treatment in older AML patients All patients should be assessed for their suitability to receive intensive induction therapy at presentation. CLINICAL TRIALS This patient population has historically contributed low recruitment to clinical trials due to ineffective therapies, adverse disease biology and physical limitations of the older AML patient. High risk, fit, older patients with high-risk APL (white cell count >10 × 10 SP 9 sp /L) can be treated with a similar treatment approach to that used in younger patients, although dose reduction should be considered with chemotherapy (especially anthracyclines)-based regimens.97-100 Patients with a high white cell count >10 × 10 SP 9 sp /L should receive prophylactic corticosteroids which can potentially reduce the risk of APL differentiation syndrome.97,99 Dexamethasone 10 mg intravenously twice a day should be started immediately at the earliest clinical suspicion of APL differentiation syndrome. An evaluation of 17 years of low dose cytarabine as therapy for AML patients not fit for intensive treatment, including patients with adverse cytogenetics, shows improving survival, potential underutilisation and highlights the need for new therapy. An analysis of 2,767 AML patients in the Swedish Acute Leukaemia Registry evaluated the effect of the decision to treat on outcomes.31 In this study, 30-day mortality rates were dependent on both age and PS; however, older patients with good PS had low early death rates and patients with poor PS had increased early mortality across all ages. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
5. Haematological evaluation of bruising and bleeding in children undergoing child protection investigation for possible physical maltreatment: A British Society for Haematology Good Practice Paper.
- Author
-
Biss, Tina, Sibson, Keith, Baker, Peter, Macartney, Christine, Grayson, Caroline, Grainger, John, Chalmers, Elizabeth, and Dixon, Sarah
- Subjects
- *
BRUISES , *CHILD welfare , *HEMORRHAGE , *HEMATOLOGY , *HEALTH facilities , *MEDICAL personnel - Abstract
The presence of multiple bleeding symptoms and/or severe bleeding symptom(s) contribute to a higher score and therefore a greater chance of a bleeding disorder diagnosis. There is bleeding at a critical site (e.g., ICH, retinal haemorrhage, gastrointestinal haemorrhage, intraspinal haemorrhage, haemarthrosis) with no correlating history of trauma or other explanation that adequately accounts for the bleeding. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. A standardised bleeding assessment tool, e.g., the International Society for Haemostasis and Thrombosis Bleeding Assessment Tool (ISTH-BAT), can be used to quantitate bleeding symptoms in order to generate a bleeding score. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
6. The use of next‐generation sequencing in the diagnosis of rare inherited anaemias: A Joint BSH/EHA Good Practice Paper*.
- Author
-
Roy, Noémi B. A., Da Costa, Lydie, Russo, Roberta, Bianchi, Paola, Mañú‐Pereira, Maria del Mar, Fermo, Elisa, Andolfo, Immacolata, Clark, Barnaby, Proven, Melanie, Sanchez, Mayka, van Wijk, Richard, van der Zwaag, Bert, Layton, Mark, Rees, David, and Iolascon, Achille
- Subjects
- *
GLUCOSE-6-phosphate dehydrogenase deficiency , *NUCLEOTIDE sequencing , *ANEMIA - Abstract
Firstly, much of globin gene testing required for pre- and neonatal diagnosis requires a rapid turnaround time and analysis of a small number of genes, making it unwieldy and unnecessary to be testing all of the genes on a panel. Diamond-Blackfan anaemia
AD RPL11 1p36.11 Ribosomal protein L11 NM 000975.5 Diamond-Blackfan anaemia 7 AD RPL15 3p24.2 Ribosomal protein L15 NM 002948.5 ? Globin gene variants are the commonest cause of inherited anaemia, and all patients should be formally assessed for their presence, using a combination of haemoglobin analysis and specific genetic tests for suspected variants, and by inclusion on NGS panels, depending on local practice. Finally, NGS-based genetic testing is useful for the identification of complex modes of inheritance that are recognised to account for at least 4% of diagnosed Mendelian conditions.20 Recommendations NGS should only be used in cases where acquired causes are thought to be very unlikely (IA) Appropriate consent should be obtained (IA) Globin gene abnormalities should be considered and investigated appropriately before NGS is carried out, including haemoglobin analysis and sequencing of individual globin genes, depending on the genetic distribution that is already known in the local population. [Extracted from the article] - Published
- 2022
- Full Text
- View/download PDF
7. Management of children and adults with all stages of nodular lymphocyte predominant Hodgkin lymphoma — All StAGEs: A consensus‐based position paper from the Hodgkin lymphoma subgroup of the UK National Cancer Research Institute.
- Author
-
Shankar, Ananth, Hall, Georgina W., McKay, Pam, Gallop‐Evans, Eve, Fielding, Patrick, and Collins, Graham P.
- Subjects
- *
HODGKIN'S disease , *CANCER research , *RESEARCH institutes , *LYMPHOCYTES , *WATCHFUL waiting - Abstract
Summary: A consensus statement for the management for patients of all ages with all stages of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) — All StAGEs — is proposed by representatives of the UK National Cancer Research Institute (NCRI) Hodgkin lymphoma study group and the Children's Cancer & Leukaemia Group. Based on current practices and published evidence, a consensus has been reached regarding diagnosis, staging and risk‐ik7 stratified management which includes active surveillance, low‐ and standard‐dose immunochemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. Richter transformation of chronic lymphocytic leukaemia: a British Society for Haematology Good Practice Paper.
- Author
-
Eyre, Toby A., Riches, John C., Patten, Piers E. M., Walewska, Renata, Marr, Helen, Follows, George, Hillmen, Peter, and Schuh, Anna H.
- Subjects
- *
CHRONIC leukemia , *RICHTER syndrome , *LYMPHOCYTIC leukemia , *HEMATOLOGY , *DIFFUSE large B-cell lymphomas , *CHRONIC lymphocytic leukemia - Abstract
RT occurs in 2-10% of CLL patients, usually during the disease course rather than at presentation, representing a transformation rate of 0-5-1% per CLL patient per year.2-5 RT should be suspected when a CLL patient develops one or more new "B symptoms", asymmetric, rapidly progressive lymphadenopathy, or a sudden lactate dehydrogenase (LDH) rise. Treatment approach Patients with RT commonly present in the context of pre-treated CLL and immunosuppression, and given the typical demographics of the CLL population, patients are often older with co-existing comorbidities.22 Treatment has historically involved multi-agent cytotoxic chemotherapy, more recently in combination with an anti-CD20 monoclonal antibody. Patients with I TP53 i aberrations or those who develop RT having previously received CLL-directed treatment have a poor outcome with R-CHOP alone, although this remains the standard of care and provides at least initial disease control for most patients. Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
9. Cytomegalovirus serological testing in potential allogeneic haematopoietic stem cell transplant recipients: A British Society for Haematology Good Practice Paper.
- Author
-
Morton, Suzy, Dignan, Fiona, Osman, Husam, Potter, Mike, Pagliuca, Tony, and Peggs, Karl S.
- Subjects
- *
HEMATOPOIETIC stem cells , *STEM cell transplantation , *SERODIAGNOSIS , *HEMATOLOGY , *BLOOD transfusion reaction , *HEMATOPOIETIC stem cell transplantation , *DIRECTED blood donations - Abstract
• Equivocal or borderline CMV IgG values in patients transfused with CMV-U components may indicate passive rather than immune acquisition of IgG and should prompt a repeat confirmatory test (Grade 1C). CMV IgG, CMV IgM and CMV polymerase chain reaction (PCR) may help in distinguishing passive transfer from actively acquired antibody. The British Society for Haematology (BSH) produces Good-Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. [Extracted from the article]
- Published
- 2021
- Full Text
- View/download PDF
10. The prevention of central nervous system relapse in diffuse large B‐cell lymphoma: a British Society for Haematology good practice paper.
- Author
-
McKay, Pamela, Wilson, Matthew R., Chaganti, Sridhar, Smith, Jeffery, Fox, Christopher P., and Cwynarski, Kate
- Subjects
- *
DIFFUSE large B-cell lymphomas , *CENTRAL nervous system , *HEMATOLOGY , *LYMPHOMAS , *CONTRAST-enhanced magnetic resonance imaging - Published
- 2020
- Full Text
- View/download PDF
11. Position paper on International Collaboration for Transfusion Medicine (ICTM) Guideline 'Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline'.
- Author
-
Trompeter, Sara, Massey, Edwin, and Robinson, Susan
- Subjects
- *
CELL differentiation , *BLOOD transfusion , *ERYTHROCYTES , *META-analysis , *GUIDELINES - Abstract
Summary: The International Collaboration for Transfusion Medicine Guidelines (ICTMG) has published guidance on transfusion for haemoglobinopathies. To give a UK perspective on this guidance, each of the recommendations in the ICTMG guideline were reviewed and the applicability for transfusion practice in the UK considered with reference to relevant published British Society for Haematology (BSH) guidelines and national standards. There was much consensus; however, there was disparity surrounding the recommendations for routinely extended matching in those with alloimmunisation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
12. The management of primary mediastinal B‐cell lymphoma: a British Society for Haematology Good Practice Paper.
- Author
-
Cwynarski, Kate, Marzolini, Maria A. V., Barrington, Sally F., Follows, George, Illidge, Timothy, Stern, Simon, and Davies, Andrew
- Subjects
- *
DIFFUSE large B-cell lymphomas , *HEMATOLOGY , *LYMPHOMAS - Abstract
The article focuses on the Good Practice Paper compiled by the British Society for Haematology (BSH) consisting of evidence regarding the management of primary mediastinal Bâ€Âcell lymphoma (PMBCL). It talks about the gene expression and the pathogenesis of PMBCL along with the impact of nuclear Factor-kB (NF-kB) pathways on the patient.
- Published
- 2019
- Full Text
- View/download PDF
13. The prevention of glucocorticoid‐induced osteoporosis in patients with immune thrombocytopenia receiving steroids: a British Society for Haematology Good Practice Paper.
- Author
-
Hill, Quentin A., Bagot, Catherine, Kanis, John A., Compston, Juliet E., Grainger, John D., Thachil, Jecko, Provan, Drew, Evans, Gillian, Garg, Mamta, and Bradbury, Charlotte
- Subjects
- *
OSTEOPOROSIS , *IDIOPATHIC thrombocytopenic purpura , *STEROIDS , *DRUG side effects , *GLUCOCORTICOIDS , *THROMBOCYTOPENIA treatment , *DIPHOSPHONATES - Abstract
The article focuses on the glucocorticoids being a risk factor causing osteoporosis in patients with immune thrombocytopenia (ITP) receiving steroids. It talks about the Good Practice Paper compiled by the British Society for Haematology (BSH) consisting of guideline for the prevention of glucocorticoid-induced osteoporosis (GIO) during the treatment of patients with ITP.
- Published
- 2019
- Full Text
- View/download PDF
14. A British Society for haematology good practice paper on the diagnosis and investigation of patients with mantle cell lymphoma.
- Author
-
McKay, Pamela, Leach, Mike, Jackson, Bob, Robinson, Stephen, and Rule, Simon
- Subjects
- *
MANTLE cell lymphoma , *MOLECULAR pathology , *POSITRON emission tomography , *COMPUTED tomography , *TUMOR classification , *PROGNOSIS , *DIAGNOSIS - Abstract
The article discusses the diagnosis and investigation of patients with mantle cell lymphoma (MCL. Topics covered include the latest information on molecular pathology, the use of positron emission tomography/computed tomography (PET/CT) scanning in staging and response assessment, and biological prognostic factors of MCL.
- Published
- 2018
- Full Text
- View/download PDF
15. The enigma of sickle cell hepatopathy: Pathophysiology, clinical manifestations and therapy.
- Author
-
Rizvi, Insia, Solipuram, Divya, Kaur, Navneet, Komel, Aqsa, Batool, Saba, and Wang, Jennifer
- Abstract
Summary Sickle cell disease (SCD) is one of the most common genetic disorders in the world predominantly affecting economically disadvantaged populations. There is a notable discrepancy between the growing adult SCD population and available diagnostic and therapeutic interventions for SCD. Sickle cell hepatopathy (SCH) is an all‐inclusive term to describe the acute and chronic liver manifestations of SCD. The pathophysiology of SCH follows no defined pattern or sequence that poses challenges to clinicians and researchers alike. Evidence is lacking for this underreported disease at various levels from diagnostic to therapeutic options. This paper reviews the basic pathophysiology, clinical features, biochemical and radiological findings of various SCH manifestations and outlines the management of each condition. Old and new therapy options in SCD including hydroxyurea, red blood cell exchange transfusion, ursodeoxycholic acid, voxelotor, l‐glutamine and crizanlizumab have been reviewed to investigate the role of these options in treating SCH. The role of liver transplant, haematopoietic stem cell transplant and gene therapy in SCH patients have been reviewed. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. Dapsone for paediatric chronic immune thrombocytopenia: Short report from a tertiary centre in South India.
- Author
-
Bharadwaj, Niteesh, Munireddy, Jyothi, Selvam, Sumithra, Bharadwaj, Vandana, and Prakash, Anand
- Subjects
- *
IDIOPATHIC thrombocytopenic purpura , *DAPSONE , *PEDIATRICS , *CHILDREN'S hospitals - Abstract
Summary: Immune thrombocytopenia (ITP) resolves in most children within 3–12 months of diagnosis. Chronic ITP affects 10%–20% of patients, some of whom require treatment. Several second‐line agents are efficacious in this group of patients. This paper describes our experience of using dapsone as a single second‐line agent in children with chronic ITP. One hundred and three children with chronic ITP were seen at our centre from January 2012 to December 2016. Forty‐five children met the inclusion criteria and received dapsone; 17 (37.8%) were boys; and 28 (62.2%) were girls. Early response to dapsone was seen in 37.8% of patients. The median duration of long‐term follow‐up was 50 months, and at least a partial response was seen in 64.4% of the patients. Dapsone offers good initial response rates and sustained remission in paediatric chronic ITP, comparable to other therapeutic agents available. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
17. Diagnosis of red cell G6PD deficiency in rural Burkina Faso. Comparison of a rapid fluorescent enzyme test on filter paper with polymerase chain reaction based genotyping.
- Author
-
Meissner, Peter E., Coulibaly, Boubacar, Mandi, Germain, Mansmann, Ulrich, Witte, Steffen, Schiek, Wolfgang, Müller, Olaf, Schirmer, R. Heiner, Mockenhaupt, Frank P., and Bienzle, Ulrich
- Subjects
- *
ANTIMALARIALS , *THERAPEUTICS , *POLYMERASE chain reaction , *HEMOLYSIS & hemolysins , *PEDIATRICS - Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals are at increased risk of developing haemolysis following treatment with various antimalarial drugs. Reliable field tests for G6PD deficiency are thus needed in chemotherapy studies and their validity has to be assessed. In two phase II clinical trials on methylene blue (MB) antimalarial therapy in rural Burkina Faso, paediatric and adult participants were tested for G6PD deficiency. The results of a haemoglobin-adjusted nicotinamide adenine dinucleotide phosphate (NADPH) fluorescence test on paper (NFP test) were compared with polymerase chain reaction (PCR)-based G6PD genotyping also using blood samples on filter papers. This is the first study comparing sensitivity and specificity of the two methods. There was good agreement between the NFP test results and the PCR findings. The estimate of the sensitivity of the NFP test was 98·2% (95·8–99·6%) and the specificity was 97·1% (94·2–99·2%). In conclusion, the NFP assay is a reliable and inexpensive method for large-scale G6PD deficiency screening in rural West Africa. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
18. GATA2 deficiency syndrome: A compensatory mechanism gone awry?
- Author
-
Rio‐Machin, Ana
- Abstract
In their paper, using zebrafish models, Gioacchino et al. have demonstrated the GATA2 haploinsufficiency, the genetic hallmark of GATA2 deficiency syndrome, promotes erythroid and myeloid cytopenia, and have discovered a self‐regulatory mechanism to compensate GATA2 levels and protein function.Commentary on: Gioacchino et al. GATA2 heterozygosity causes an epigenetic feedback mechanism resulting in myeloid and erythroid dysplasia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19585. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. The importance of ABO in platelet refractoriness, an often overlooked option.
- Author
-
Gammon, Richard and Mo, Allison
- Subjects
- *
BLOOD platelets , *PLATELET count , *BLOOD platelet transfusion , *BLOOD transfusion - Abstract
ABO‐non‐identical (ni) platelets provide less of an increase in platelet count and may increase the length of patient transfusions. The paper by Han and Badami showed that ABO‐ni platelets may be a risk factor for immune platelet transfusion refractoriness. Commentary on: Han et al. ABO non‐identical platelet transfusions, immune platelet refractoriness and platelet support. Br J Haematol 2024;204:2097‐2102. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
20. research paper Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection.
- Author
-
Hellberg, Å., Ringressi, A., Yahalom, V., Säfwenberg, J., Reid, M. E., and Olsson, M. L.
- Subjects
- *
GENETIC mutation , *BLOOD , *GENETICS , *PHENOTYPES , *DNA , *GLYCOLIPIDS - Abstract
The aim of this study was to further explore the molecular genetic bases of the clinically important but rare blood group phenotypes p, p1k and p2k by analysis of the 4-α-galactosyltransferase (Pk) and 3-β-N-acetylgalactosaminyltrans- ferase (P) genes responsible for synthesis of the related pk (Gb3) and p (Gb4) antigens respectively. Lack of these glycolipid moieties is associated with severe transfusion reactions and recurrent spontaneous abortions but also offers immunity against certain infectious agents. Blood samples from 20 p and p1k or p2k individuals of different geographic and ethnic origin were investigated. DNA sequencing by capillary electrophoresis was performed following amplification of the coding regions in the Pk or P genes. In the pk gene, nine novel and five previously described mutations were detected. One of the newly found mutations introduced an immediate stop, five shifted the reading frame introducing premature stop codons and three were missense mutations causing amino acid substitutions in conserved regions of the transferase. Four new and two previously described mutations in the P gene were found. Three of the novel alleles reported here carried nonsense mutations whilst the fourth allele had a missense mutation. The finding of 13 novel mutations in 14 alleles emphasizes further the genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
21. research paper Phosphatidylinositol-3 kinase inhibitors reproduce the selective antiproliferative effects of imatinib on chronic myeloid leukaemia progenitor cells.
- Author
-
Marley, S. B., Lewis, J. L., Schneider, H., Rudd, C. E., and Gordon, M. Y.
- Subjects
- *
PHOSPHOINOSITIDES , *MYELOID leukemia , *NONLYMPHOID leukemia , *CELL proliferation , *CELL growth , *PATIENTS - Abstract
We investigated the role of the phosphatidylinositol-3 kinase (PI-3K) pathway in regulating the proliferation of primary chronic myeloid leukaemia (CML) progenitor cells by using imatinib to inhibit the activity of p210Bcr-Abl. The effect of imatinib on the expression of PI-3K pathway proteins was investigated by kinase assays and Western blotting; PI-3K was inhibited by wortmannin or LY294002, Jak2 by AG490 and farnesylation by FTI II; progenitor cell proliferation (self-renewal) was measured by growing myeloid colonies in vitro, then replating them to observe secondary colony formation. Suppression of p210Bcr-Abl with imatinib indirectly suppressed the activity of PI-3K and its downstream targets (Erk, Akt and p70S6 kinase), thereby implicating the PI-3K pathway in p210Bcr-Abl-mediated signalling in primary CML progenitor cells. The PI-3K inhibitors, wortmannin and LY294002 reproduced the differential effects of imatinib on normal and CML progenitor cell proliferation in vitro by increasing normal cell (P = 0.001) and reducing CML cell proliferation (P = 0.0003). This differential effect was attributable to dysregulated signalling by granulocyte colony-stimulating factor in CML. The responses of individual patient's cells to wortmannin correlated with their responses to imatinib (P = 0.004) but not their responses to AG490 (Jak2 kinase inhibitor) or FTI II (farnesyltransferase inhibitor). Individual responses to wortmannin also correlated with responses to interferon α (IFNα) (P = 0.016). Imatinib-resistant K562 cells were sensitive to LY294002. Inhibition of the PI-3K pathway may be common to imatinib and IFNα and reflect dysregulated cytokine signalling. As imatinib-resistant cells remained sensitive to wortmannin and LY294002, targeting the PI-3K pathway may provide an alternative therapy for imatinib-resistant patients. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
22. research paper Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virus-associated Hodgkin's disease.
- Author
-
Hoffmann, Christian, Kai Uwe Chow, Wolf, Eva, Faetkenheuer, Gerd, Stellbrink, Hans-Juergen, Van Lunzen, Jan, Jaeger, Hans, Stoehr, Albrecht, Plettenberg, Andreas, Wasmuth, Jan-Christian, Rockstroh, Juergen, Mosthaf, Franz, Horst, Heinz-August, and Brodt, Hans-Reinhard
- Subjects
- *
HODGKIN'S disease , *ANTIRETROVIRAL agents , *ANTIVIRAL agents , *HIV , *IMMUNODEFICIENCY , *PROGNOSIS - Abstract
Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected patients. We analysed the outcome of patients with HIV- associated HD (HIV-HD) with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and other prognostic factors. To evaluate the effects of several variables on overall survival (OS), Kaplan-Meier statistics and extended Cox regression analysis were performed. Response to HAART was used as a time-dependent variable and was defined as an increase of>01× 109 CD4 cells/I and/or at least one viral load <500 copies/mI during the first 2 years following diagnosis of HIV-HD. Fifty-seven patients with HIV-HD diagnosed between 1990 and 2002 were included in the study. In the Cox model, the only factors independently associated with OS were HAART response [relative hazard (RH) 019; 95% confidence interval (CI) 0.06-060], complete remission (RH 0.30, 95% CI 0.13-0.72), and age ≤45 years (RH 0.23; 95% CI 0.09-0.60). Median survival time in patients without HAART response was 186 months, whereas the median survival time in patients with HAART response was not reached (89% OS at 24 months). In this cohort, a significant improvement in survival was found in patients with HIV-HD who responded to HAART. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
23. research paper FLT-3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact.
- Author
-
Au, Wing Y., Alvin Fung, Chim, Chor S., Lie, Albert K., Liang, Raymond, Ma, Edmond S. K., Chan, Cheuk H., Wong, Kit F., and Kwong, Yok L.
- Subjects
- *
GENETIC mutation , *GENETICS , *POLYMERASE chain reaction , *BLOOD cells , *DNA , *MORPHOLOGY - Abstract
FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation-loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT-3 aberrations in a cohort of APL patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the lTD was recognized as an increase in the size of the PCR product. FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; lTD + D835 mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT-3 lTD to be associated with non-remission (P = 0.06). For disease-free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT-3 lTD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT-3 inhibitors in the treatment of APL. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
24. research paper Hydrogen peroxide in the Burkitt's lymphoma cell line Raji provides protection against arsenic trioxide-induced apoptosis via the phosphoinositide-3 kinase signalling pathway.
- Author
-
Di Lu, Xiao-chun Bai, Li Gui, Yong-Chun Su, Fan Deng, Bin Liu, Xiu-Mei Li, Wei-Sen Zeng, Bao-Luan Cheng, and Shen-Qiu Luo
- Subjects
- *
HYDROGEN peroxide , *LYMPHOMAS , *RETICULOENDOTHELIAL granulomas , *APOPTOSIS , *CELL death , *CELL culture - Abstract
Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined the effects of hydrogen peroxide (H2O2) on arsenic trioxide (As2O3)-induced cell killing. Low concentrations of H2O2 (200 μmol/l) inhibited the ability of As2O3 to induce apoptosis in the Burkitt's lymphoma cell line Raji. H2O2 altered the form of cell death from apoptosis to pyknosis/ necrosis and also lowered the degree of cell killing by As2O3. H2O2 was capable of preventing caspase-3 activation induced by As2O3 in Raji cells. Incubation of cells with a phosphoinositide-3 kinase (PI-3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H2O2 on As2O2-induced caspase-3 activation. In addition, the PI-3K inhibitor partially blocked the effects of H2O2 on up-regulation of Bcl-2 and Bcl-X1. protein expression, down-regulation of Bax protein expression, and phosphorylation of Bcl-2 and IκBα. This investigation demonstrated for the first time that low concentrations of H2O2 provide protection against the in vivo of As2O3- induced apoptosis. PI-3K plays a crucial role in enhancing cell survival during H2O2, inhibiting As2O3-induced apoptosis in the Burkitt's lymphoma cells. As2O3-induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
25. research paper Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma.
- Author
-
Hussein, Mohamad A., Saleh, Mansoor, Ravandi, Farhad, Mason, James, Rifkin, Robert M., and Ellison, Ralph
- Subjects
- *
MULTIPLE myeloma , *MYELOMA proteins , *TUMOR proteins , *PLASMACYTOMA , *CLINICAL medicine , *ARSENIC - Abstract
Despite aggressive and innovative therapy, patients with multiple myeloma (MM) invariably relapse and die of their disease. New options for non- cytotoxic salvage therapy and additional therapeutic strategies are needed. Arsenic trioxide, an antitumour agent with a multifaceted mechanism of action, induces apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients and, in preliminary studies, displayed clinical activity in patients with late-stage MM. A phase 2, multicentre, open-label study of arsenic trioxide was conducted in 24 MM patients; eight had relapsed and 16 were refractory to prior therapy. Patients received arsenic trioxide 025 mg/kg/d for 5 d/week during the first 2 weeks of each 4-week cycle. Sixteen patients had grade 3 or 4 neutropenia and one required antibiotics. Reductions (25% or more) in serum M-protein levels occurred in eight of 24 (33%) patients. An additional six (25%) patients had stable disease. The median time to response was 675 d, with a median duration of response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in two patients with high baseline values. These data indicate that arsenic trioxide is active and reasonably well tolerated as a single-agent salvage therapy, even in patients with late-stage, relapsed and refractory MM. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
26. research paper Prophylactic effect of recombinant factor VIIa in factor VII deficient patients.
- Author
-
Mathijssen, Natascha C. J., Masereeuw, Rosalinde, Verbeek, Kitty, Lavergne, J. Maurice, Costa, Jean-Marc, Van Heerde, Waander L., and Nováková, Irena R. O.
- Subjects
- *
BLOOD plasma , *HEMORRHAGE , *PATIENTS , *GENETIC mutation , *GENETICS , *PHENOTYPES - Abstract
Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder associated with a bleeding tendency. We describe three patients with congenital FVII deficiency who have been treated with activated recombinant factor VII (rVIIa). Two patients had novel mutations and were treated prophylactically with P2 mg rVIIa two to three times a week. Patients I and 2 had a severe bleeding tendency. The frequency and severity of bleeding decreased by treatment with rVIIa compared with similar treatment with plasma-derived FVII. The third patient with a moderate bleeding phenotype was treated on demand and showed no change in the frequency of bleeding upon treatment with rVIIa or plasma products. The beneficial effect of rVIIa cannot be explained by the rVIIa half-lives. Pharmacokinetical analysis showed rVIIa activity half-lives of 35, 50 and 54 mm for patients 1, 2 and 3, respectively. In conclusion, prophylactic treatment of FVII deficient patients with rVIIa appears to be applicable, safe and successful, although the mechanism of action remains to be elucidated. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
27. research paper Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients.
- Author
-
Tanimoto, Tetsuya E., Yamaguchi, Takuhiro, Tanaka, Yuji, Saito, Akiko, Tajima, Kinuko, Karasuno, Takahiro, Kasai, Masanobu, Kishi, Kenji, Mori, Takehiko, Maseki, Nobuo, Monishima, Satoko, Miyakoshi, Shigesaburo, Kasai, Masaharu, Ohno, Yuju, Sung-Won Kim, Numata, Akihiko, Kami, Masahiro, Takaue, Yoichi, Mori, Shin-Ichiro, and Harada, Mine
- Subjects
- *
BONE marrow transplantation , *BONE marrow , *STEM cells , *BLOOD , *BLOOD cells - Abstract
A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen- identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 374% for PBSCT and 320% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 001). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
28. research paper Four pedigrees of the cation-leaky hereditary stomatocytosis class presenting with pseudohyperkalaemia. Novel profile of temperature dependence of Na+–K+ leak in a xerocytic form.
- Author
-
Gore, D. M., Layton, Mark, Shina, A. K., Williamson, P. J., Vaidya, Bijay, Connolly, V., Mannix, P., Chetty, M. C., Nicolaou, Anna, and Stewart, G. W.
- Subjects
- *
ORAL medicine , *HEMATOLOGY , *ERYTHROCYTES , *SODIUM , *POTASSIUM , *BLOOD - Abstract
We report four pedigrees of the group of Na+-K+-leaky red cell disorders of the 'hereditary stomatocytosis' class. Each showed pseudohyperkalaemia because of temperature-dependent loss of K+ from red cells on storage of whole blood at room temperature. All pedigrees showed an abnormality in the temperature dependence of the 'passive leak' of the membrane to K+. Two pedigrees, both of which showed a compensated haemolytic state with dehydrated red cells and target cells on the blood film, showed a novel pattern, in which the profile was flat between 37°C and about 32°C then dropped as the temperature was reduced to zero. The third showed the 'shallow slope' profile, with stomatocytes on the blood film and very markedly abnormal intracellular Na+ and K+ levels. Minimal haemolysis was present. The fourth pedigree, of Asian origin, showed the shoulder pattern (minimum at 32°C, maximum at 12°C) with essentially normal haematology. Both of these latter two forms have previously been seen in other pedigrees. The first variant represents a novel kind of temperature dependence of the passive leak found in these pedigrees presenting with pseudohyperkalaemia. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
29. research paper The London Cord Blood Bank: analysis of banking and transplantation outcome.
- Author
-
Davey, Sue, Armitage, Sue, Rocha, Vanderson, Garnier, Federico, Brown, Juliette, Brown, Colin J., Warwick, Ruth, Fejily, Deidre, Watt, Suzanne, Gluckman, Eliane, Vora, Ajay, Contreras, Marcela, and Navarrete, Cristina V.
- Subjects
- *
CORD blood , *BLOOD banks , *HEMATOPOIETIC stem cells , *BLOOD cells , *ANEMIA , *BLOOD diseases - Abstract
Cord blood units ( n = 5500) stored at the London Cord Blood Bank, including 59 units transplanted into a high risk and heterogeneous group of patients, were analysed. Transplant outcome data was available for 44 patients with a median clinical follow-up of 14 months (range 3–44 months). Over 40% of the collected units were of ethnic minority origin with a median volume of 79 ml (range 40–240 ml) and a median total nucleated cell (TNC) count of 11·9 × 109/l (range 10·0–24·8 × 109/l). The average patient's weight was 28 kg (range 5–80 kg) and the median age was 8 years (range 0·7–40 years). The median number of nucleated cells infused was 4 × 107/kg (range 1·10–16 × 107/kg). Neutrophil engraftment of 0·5 × 109/l was observed in 33 (74±%) patients with an average time of 28 days (range 11–60). The Kaplan-Meier estimate of acute graft-versus-host disease (grade II >) at day 100 was 37 ± 7% and in 27 (62%) patients, it was grade I or absent. The overall survival and disease-free survival at 2 years was 49 ± 8% and 41 ± 8%, respectively. Two years after transplantation the survival rate was 69% and 54% for patients receiving a 6/6 or 5/6 HLA matched units, respectively. Infection was the main cause of transplanted related mortality in these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
30. research paper The Bcl-2 family member Bfl-1/A1 is strongly repressed in normal and malignant plasma cells but is a potent anti-apoptotic factor for myeloma cells.
- Author
-
Tarte, Karin, Jourdan, Michel, Veyrune, Jean Luc, Berberich, Ingolf, Fiol, Geneviève, Redal, Nicole, Shaughnessy Jr., John, and Klein, Bernard
- Subjects
- *
PLASMA cells , *B cell differentiation , *APOPTOSIS , *MYELOMA proteins , *CELL lines , *GENE expression - Abstract
Terminal B-cell differentiation is a multi-step process, from short-lived plasmablasts to mature long-lived plasma cells (PC). The anti-apoptotic Bcl-2 family member Bfl-1/A1 plays a critical role in the survival of mature B cells. However, its potential involvement at the later stages of B-cell development remains highly controversial. Our aim was thus to clarify the place of Bfl-1/A1 in the biology of normal PC and in the pathogenesis of multiple myeloma (MM), the major PC dyscrasia. Using gene expression profiling and quantifiable reverse transcription polymerase chain reaction experiments, we found a similar down-regulation of Bfl-1/A1 in both normal immature plasmablasts and mature PC when compared with B cells. In myeloma cells, the level of Bfl-1/A1 was low and Bfl-1/A1 was not a nuclear factor κB-inducible gene. Collectively, these data demonstrate that Bfl-1/A1 is not involved in the prolonged survival of normal mature PC, and that Bfl-1/A1 deregulation is not a common oncogenic event in MM. However, overexpression of Bfl-1/A1 by retroviral transduction promoted autonomous survival of an interleukin-6-dependent myeloma cell line and rendered it less sensitive to dexamethasone. Thus, Bfl-1/A1 transduction could be an interesting tool to obtain myeloma cell lines from primary samples and to favour the in vitro generation of antibody-secreting, long-lived normal PC. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
31. research paper t(11;18)(q21;q21) of mucosa-associated lymphoid tissue lymphoma results from illegitimate non-homologous end joining following double strand breaks.
- Author
-
Liu, Hongxiang, Hamoudi, Rifat A., Ye, Hongtao, Ruskone-Fourmestraux, Agnes, Dogan, Ahmet, Isaacson, Peter G., and Du, Ming-Qing
- Subjects
- *
MUCOSA-associated lymphoid tissue lymphoma , *CHROMOSOME abnormalities , *GENES , *INTRONS , *POLYMERASE chain reaction , *GENETIC recombination - Abstract
t(11;18)(q21;q21) is the most frequent chromosomal aberration specifically associated with mucosa-associated lymphoid tissue (MALT) lymphoma. The translocation fuses the API2 gene to the MALT1 gene and generates a functional API2-MALT1 transcript. The breakpoint of the fusion gene is well characterized at the transcript level but poorly understood at the genomic level and the mechanism underlying the translocation is unknown. We identified the genomic breakpoint in 19 t(11;18)-positive MALT lymphoma cases by polymerase chain reaction and sequencing and analysed the junctional sequences. The breakpoints were scattered in intron 7 and exon 8 of the API2 gene, and introns 4, 6, 7 and 8 of the MALT1 gene. Comparative sequence analysis between the API2-MALT1 fusion on der(11) and the MALT1-API2 fusion on der(18) showed extensive alterations including deletions, duplications and non-template-based insertions at the fusion junctions in all cases examined. An extensive sequence search failed to reveal any known sequence motifs that might be associated with chromosomal recombination or any novel consensus sequences at or near the breakpoints on both der(11) and der(18) except in one case, in which Alu repeats spanned the breakpoint of the MALT1-API2 fusion. Our results suggest that t(11;18) may result from illegitimate non-homologous end joining following double strand breaks. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
32. research paper Frequent HPRT mutations in paroxysmal nocturnal haemoglobinuria reflect T cell clonal expansion, not genomic instability.
- Author
-
Chen, Guibin, Zeng, Weihua, Green, Spencer, and Young, Neal S.
- Subjects
- *
PAROXYSMAL hemoglobinuria , *LESCH-Nyhan syndrome , *LYMPHOCYTES , *T cells , *CELL receptors , *CELL proliferation - Abstract
Paroxysmal nocturnal haemoglobinuria (PNH) results from acquired mutations in the PIG-A gene of an haematopoietic stem cell, leading to defective biosynthesis of glycosylphosphatidylinositol (GPI) anchors and deficient expression of GPI-anchored proteins on the surface of the cell's progeny. Some laboratory and clinical findings have suggested genomic instability to be intrinsic in PNH; this possibility has been supported by mutation analysis of hypoxanthine-guanine phosphoribosyltransferase ( HPRT) gene abnormalities. However, the HPRT assay examines lymphocytes in peripheral blood (PB), and T cells may be related to the pathophysiology of PNH. We analysed the molecular and functional features of HPRT mutants in PB mononuclear cells from eleven PNH patients. CD8 T cells predominated in these samples; approximately half of the CD8 cells lacked GPI-anchored protein expression, while only a small proportion of CD4 cells appeared to derive from the PNH clone. The HPRT mutant frequency (Mf) in T lymphocytes from PNH patients was significantly higher than in healthy controls. The majority of the mutant T lymphocyte clones were of CD4 phenotype, and they had phenotypically normal GPI-anchored protein expression. In PNH patients, the majority of HPRT mutant clones were contained within the V β2 T cell receptor (TCR) subfamily, which was oligoclonal by complementarity-determining region three (CDR3) size analysis. Our results are more consistent with detection of uniform populations of expanded T cell clones, which presumably acquired HPRT mutations during antigen-driven cell proliferation, and not due to an increased Mf in PNH. HPRT mutant analysis does not support underlying genomic instability in PNH. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
33. research paper B-prolymphocytic leukaemia with t(11;14) revisited: a splenomegalic form of mantle cell lymphoma evolving with leukaemia.
- Author
-
Ruchlemer, Rosa, Parry-Jones, Nilima, Brito-Babapulle, Vasantha, Attolico, Imma, Wotherspoon, Andrew C., Matutes, Estella, and Catovsky, Daniel
- Subjects
- *
LYMPHOCYTIC leukemia , *CYCLINS , *BONE marrow , *CYTOGENETICS , *IMMUNOHISTOCHEMISTRY , *IMMUNOGLOBULINS - Abstract
We reviewed eight cases that were diagnosed before 1995 with B-prolymphocytic leukaemia (B-PLL) harbouring t(11;14)(q13;q32) and/or cyclin D1 staining. Thirteen B-PLL patients without t(11;14) were selected as controls. Peripheral blood, bone marrow and histological sections were re-examined without cytogenetic information. Final diagnosis was made using morphology, cytogenetics, immunophenotype and immunohistochemistry. Clinical characteristics were similar for both groups except for younger age, male predominance and extranodal involvement in cases with t(11;14). CD5 was more frequently positive in the t(11;14)+ group (80%) than in the t(11;14)− group (31%). Surface membrane immunoglobulin was strongly expressed by all t(11;14)+ cases, but only 45% of t(11;14)− cases. Histopathological and cytological review of cases with t(11;14) showed an infiltrate with a mixture of cells, some resembling prolymphocytes and others with mantle cell lymphoma (MCL) morphology. Blood films of cases with t(11;14) showed features suggestive of B-PLL in three, and in others, a mixture of cells resembling MCL and nucleolated ones; none corresponded to the blastoid form of MCL. We suggest that ‘B-PLL’ with t(11;14) may represent a splenomegalic form of MCL evolving with leukaemia. These cases illustrate the importance of tissue diagnosis with cyclin D1 staining and fluorescence in situ hybridization analysis in B-cell leukaemia with prolymphocytic features. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
34. research paper Aspergillus fumigatus antigens activate innate immune cells via toll-like receptors 2 and 4.
- Author
-
Braedel, Sibylla, Radsak, Markus, Einsele, Hermann, Latgé, Jean-Paul, Michan, Andreas, Loeffler, Juergen, Haddad, Ziad, Grigoleit, Ulrich, Schild, Hansjoerg, and Hebart, Holger
- Subjects
- *
ASPERGILLOSIS , *ASPERGILLUS fumigatus , *NATURAL immunity , *DENDRITIC cells , *IMMUNE system , *GRANULOCYTES , *MONOCYTES , *HISTOCOMPATIBILITY - Abstract
Invasive aspergillosis (IA) is a leading cause of mortality in haematological patients. Appropriate activation of the innate immune system is crucial for the successful clearance of IA. Therefore, we studied the Aspergillus fumigatus-mediated activation of human granulocytes and monocyte-derived immature dendritic cells (DCs), as well as murine bone marrow-derived DCs (BMDCs) from wild type, toll-like receptor (TLR)4-deficient, TLR2 knockout, and TLR2/TLR4 double deficient mice. Aspergillus fumigatus antigens induced the activation and maturation of immature DCs as characterized by CD83 expression, upregulation of major histocompatibility complex and co-stimulatory molecules. Moreover, fungal antigens enhanced the phagocytosis and production of interleukin (IL)-8 in granulocytes. The release of IL-12 by BMDCs in response to A. fumigatus antigens was dependent on the expression of TLR2, whereas the release of IL-6 was dependent on the expression of functional TLR4 molecules. The protein precipitate of A. fumigatus supernatant provided strong stimulation of DCs and granulocytes, indicating that a factor secreted by A. fumigatus might activate innate immune cells. In conclusion, A. fumigatus antigens induced the activation of DCs and granulocytes. Our results indicated that this activation was mediated via TLR2 and TLR4. Future studies are needed to assess the clinical impact of these findings in patients at high risk for IA. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
35. research paper Clinical and molecular cytogenetic studies in seven patients with myeloid diseases characterized by i(20q−).
- Author
-
Li, Tianyu, Xue, Yongquan, Wu, Yafang, and Pan, Jinlan
- Subjects
- *
MYELODYSPLASTIC syndromes , *MYELOID leukemia , *FLUORESCENCE in situ hybridization , *PROGNOSIS , *CHROMOSOMES , *KARYOTYPES , *BONE marrow cells - Abstract
We report on seven patients with myeloid diseases characterized by i(20q−) anomaly. Four patients were male and three were female, their median age was 57 years. The diagnosis at presentation was myelodysplastic syndrome in six patients, acute myeloid leukaemia in one patient. Four died but three survived and remain anaemic. The survivals were 6 months for patient 1, 7 months for patient 2, 17 d for patient 4 and 28 d for patient 5. Chromosome specimens were prepared by direct and/or short-term culture of bone marrow cells. Karyotype analysis was performed by R- and G-banding technique, which showed that one of the normal chromosomes 20 was substituted by one or two small metacentric chromosomes in all seven patients. The karyotype was ider(20)(q10)del(20)(q11q13), i.e. i(20q−) in six patients by dual-colour fluorescence in situ hybridization assay using two probes (a subtelomeric probe for 20q and an unique probe for 20q12). As far as we know, this anomaly has not been reported previously. Thus, we consider that i(20q−) is a novel and rare recurrent chromosomal abnormality that is specifically associated with myeloid diseases and may indicate a poor prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
36. research paper Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma.
- Author
-
Raje, Noopur, Hideshima, Teru, Davies, Faith E., Chauhan, Dharminder, Treon, Steven P., Young, Gloria, Tai, Yu-Tzu, Avigan, David, Gong, Jianlin, Schlossman, Robert L., Richardson, Paul, Kufe, Donald W., and Anderson, Kenneth C.
- Subjects
- *
IMMUNOTHERAPY , *CANCER cells , *DENDRITIC cells , *VACCINES , *MULTIPLE myeloma , *LYMPHOCYTES , *T cells - Abstract
Multiple myeloma (MM) cells express certain tumour-associated antigens (TAAs) that could serve as targets for active-specific immunotherapy. The aim of the present study was to test the MM/dendritic cell (DC) fusion as a vaccination strategy. We fused MM cells with DC to generate fusion cells (FCs) and tested their antigen presenting cell (APC) function in mixed lymphocyte reactions and cytotoxicity assays. First, the HS Sultan and SK0-007 HAT sensitive human MM cell lines and DCs generated from peripheral blood of normal donors were fused in the presence of 50% polyethylene glycol to form FCs. Next, tumour cells freshly isolated from patients were similarly fused with autologous DCs to generate FCs. The FCs demonstrated a biphenotypic profile, confirmed both by flow-cytometry and dual immunofluorescence microscopy. These FCs induced MM-specific cytotoxicity. FCs, but not MM cells or DCs alone, were potent stimulators of autologous patient T cells. More importantly, FC-primed autologous peripheral blood mononuclear cells demonstrated major histocompatibility complex-restricted MM-specific cytolysis. These studies therefore demonstrated that MM/DC FC can trigger an autologous immune response to MM cells and formed the framework for a clinical trial currently underway. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
37. research paper Early response predicts thalidomide efficiency in patients with advanced multiple myeloma.
- Author
-
Waage, Anders, Gimsing, Peter, Juliusson, Gunnar, Turesson, Ingemar, Gulbrandsen, Nina, Eriksson, Tommy, Hjorth, Martin, Nielsen, Johan Lanng, Lenhoff, Stig, Westin, Jan, and Wislöff, Finn
- Subjects
- *
THALIDOMIDE , *MULTIPLE myeloma , *PREDNISONE , *DRUG therapy , *STEM cells , *HEMOGLOBINS - Abstract
Sixty-five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0·200/h, 0·140/h, 0·886 l/kg, 0·126 l/h/kg and 4·98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
38. research paper The role of matrix metalloproteinase 9 in the pathogenesis of chronic lymphocytic leukaemia.
- Author
-
Kamiguti, Aura S., Lee, Edwin S., Till, Kathleen J., Harris, Robert J., Glenn, Mark A., Ke Lin, Mark A., Hai Juan Chen, Mark A., Zuzel, Mirko, and Cawley, John C.
- Subjects
- *
LYMPHOCYTIC leukemia , *METALLOPROTEINASES , *CARCINOGENESIS , *LYMPHOCYTES , *SECRETION , *ENZYMES - Abstract
Matrix metalloproteinases (MMPs) are important for the pathogenesis and progression of different tumours. MMPs-2 and -9 are the principal MMPs produced by lymphocytes; these enzymes can degrade a number of matrix proteins but are the two main MMPs that digest type IV collagen, the major component of basement membranes. Therefore, these enzymes are potentially important for tissue invasion and remodelling by malignant lymphocytes. This study showed that chronic lymphocytic leukaemia (CLL) cells produce and secrete variable amounts of pro-MMP-9, but no MMP-2 or tissue inhibitor of metalloproteinase 1 (TIMP-1). The pro-enzyme was found in monomeric and dimeric forms and also complexed with lipocalin. Moreover, a small fraction of secreted monomer became associated with the cell surface and activated upon cell adhesion to insolubilized type IV collagen. High levels of intracellular MMP-9 were associated with advanced (stage C) disease and with poor patient survival. Immunohistochemical studies demonstrated that MMP-9 was associated with areas of tissue invasion and remodelling. The relatively specific MMP-9 inhibitors, Ro31-9790 (3 μmol/l) and TIMP-1, reduced CLL-cell migration through type IV collagen and through endothelial monolayers suggesting that the enzyme may also be important in malignant cell entry and egress to and from involved tissue. Our data raise the possibility that MMP-9 modulation may have therapeutic potential in advanced CLL. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
39. research paper The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura.
- Author
-
Cooper, Nichola, Stasi, Roberto, Cunningham-Rundles, Susanna, Feuerstein, Michael A., Leonard, John P., Amadori, Sergio, and Bussel, James B.
- Subjects
- *
THROMBOPENIC purpura , *BLOOD cells , *MONOCLONAL antibody probes , *BLOOD diseases , *IMMUNOGLOBULINS , *CLINICAL trials , *SPLENECTOMY - Abstract
Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts <30 × 109/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m2 weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count >50 × 109/l: 18 achieved a complete response (CR: platelet count >150 × 109/l) and 13 a partial response (PR: platelet count 50–150 × 109/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72·5 weeks; 15 of 16 are >1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1–2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to <0·03 × 109/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
40. research paper CD90/Thy-1 is preferentially expressed on blast cells of high risk acute myeloid leukaemias.
- Author
-
Buccisano, Francesco, Rossi, Francesca Maria, Venditti, Adriano, Del Poeta, Giovanni, Cox, Maria Christina, Abbruzzese, Elisabetta, Rupolo, Maurizio, Berretta, Massimiliano, Degan, Massimo, Russo, Stefania, Tamburini, Anna, Maurillo, Luca, Del Principe, Maria Ilaria, Postorino, Massimiliano, Amadori, Sergio, and Gattei, Valter
- Subjects
- *
MYELOID leukemia , *BACTERIAL transformation , *CD antigens , *CANCER patients , *THY-1 antigen , *GENE expression - Abstract
Different transformation mechanisms have been proposed for elderly acute myeloid leukaemia (AML) and secondary AML (sAML) when compared with de novo AML or AML of younger patients. However, little is known regarding differences in the immunophenotypic profile of blast cells in these diseases. We systematically analysed, by flow cytometry, 148 patients affected by de novo (100 cases) or sAML (48 cases). By defining a cut-off level of 20% of CD34+ cells co-expressing CD90, the frequency of CD90+ cases was higher in sAML (40%) versus de novo AML (6%, P < 0·001), elderly AML (>60 years) (24%) versus AML of younger patients (10%, P = 0·010) and poor- versus good-risk karyotypes (according to the Medical Research Council classification, P < 0·001). The correlation between CD90 expression, sAML and unfavourable karyotypes was confirmed by analysing the subset of CD34+ AML cases alone (91/148). Consistently, univariate analysis showed that expression of CD90 was statistically relevant in predicting a shorter survival in CD90+ AML patients ( P = 0·042). Our results, demonstrating CD90 expression in AML with unfavourable clinical and biological features, suggest an origin of these diseases from a CD90-expressing haemopoietic progenitor and indicate the use of CD90 as an additional marker of prognostic value in AML. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
41. research paper Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma.
- Author
-
Khan, S. B., Maududi, T., Barton, K., Ayers, J., and Alkan, S.
- Subjects
- *
MULTIPLE myeloma , *HISTONE deacetylase , *ENZYME inhibitors , *PEPTIDES , *INTERLEUKINS , *CANCER cells - Abstract
Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)-6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL-2 family proteins (BCL-2, BCL-XL, BAX and MCL-1) were also investigated. In addition, the RPMI 8226 cell line (IL-6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time- and dose-dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL-2, BCL-XL and MCL-1 showed decreased expression in depsipeptide-treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
42. research paper Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation.
- Author
-
Dong Hwan Kim, Jong Gwang Kim, Georg H., Sang Kyun Sohn, Georg H., Woo Jin Sung, Georg H., Jang Soo Suh, Georg H., Kun Soo Lee, Georg H., and Kyu Bo Lee, Georg H.
- Subjects
- *
LYMPHOCYTES , *BLOOD cell count , *STEM cell transplantation , *CANCER cells , *COMPLICATIONS from organ transplantation , *DISEASE relapse , *CD4 antigen - Abstract
The role of repopulating lymphocytes after allogeneic stem cell transplantation (SCT) includes the prevention of serious infections and attacking residual tumour cells in the early post-transplant phase. Therefore, the current study analysed the role of the absolute lymphocyte count (ALC) on day 21 after SCT in predicting transplant outcomes of 82 patients in terms of the risk of opportunistic infections and recurrence of original disease. The median dose of CD34+, CD3+ and mononuclear cells (MNC) infused was 6·41 × 106/kg, 1·96 × 108/kg and 6·81 × 108/kg respectively. The high ALC group (high ALC on day 21; ≥0·35 × 109/l) was associated with the use of peripheral blood stem cells, matched sibling donors and higher cell doses of MNC, CD3+ and CD4+ cells. The high ALC group also exhibited a better overall survival (56·3% vs. 17·7%) and disease-free survival (50·1% vs. 15·9%) after 3 years and lower incidences of relapse (33·6% vs. 67·1%) and fungal infections (3·0% vs. 19·5%) after 1 year. The incidence of cytomegalovirus antigenaemia was lower in the high ALC group (47·7% vs. 73·7%). Accordingly, identifying the ALC on day 21 would appear to be a useful and simple measurement to predict those patients with a high risk of opportunistic infections and relapse after allogeneic SCT. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
43. research paper Early response to therapy and survival in multiple myeloma.
- Author
-
Schaar, C. G., Kluin-Nelemans, J. C., le Cessie, S., Franck, P. F. H., te Marvelde, M. C., and Wijermans, P. W.
- Subjects
- *
MULTIPLE myeloma , *CANCER treatment , *DRUG therapy , *MONOCLONAL antibodies , *IMMUNOGLOBULIN M , *PREDNISONE - Abstract
Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan–prednisone therapy (MP: melphalan 0·25 mg/kg, prednisone 1·0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease ( n = 18), immunoglobulin M (IgM)-MM ( n = 1) and no immunotyping ( n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
44. research paper Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity.
- Author
-
Orfali, Karen A., Ohene-Abuakwa, Yaw, and Ball, Sarah E.
- Subjects
- *
ANEMIA , *GENETIC polymorphisms , *GENETIC mutation , *BLOOD diseases , *BONE marrow transplantation , *PATIENTS - Abstract
A detailed family study was undertaken of patients notified to the UK Diamond Blackfan Anaemia (DBA) Registry. RPS19 mutations were detected in 16 of 104 families, including two patients with deletions detected by intragenic loss of heterozygosity of tightly linked polymorphisms. In two further cases, polymorphisms were used to determine the parental allele of origin of RPS19 point mutations. A review of clinical details of patients with mutations and patients in the literature having identical or equivalent mutations revealed evidence for a genotype:phenotype correlation with respect to the prevalence of physical anomalies, and the occurrence of mild or variable haematological severity. Nine of 60 patients had a known family history of DBA. Haematological abnormalities, including raised red cell adenosine deaminase activity, were found in first-degree relatives of 16 of 51 (31%) of patients not previously considered to have familial DBA. Results of both parents and any siblings were normal in only 35 of 60 (58%) of cases, who were therefore assumed to have sporadic de novo DBA. The classical inheritance pattern for DBA is autosomal dominant; however, 12 of 60 families (20%) had more than one affected child despite normal results in both parents. These results have important implications for genetic counselling, and for the selection of potential sibling bone marrow donors. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
45. research paper A recombinant bispecific single-chain Fv antibody against HLA class II and FcγRIII (CD16) triggers effective lysis of lymphoma cells.
- Author
-
Bruenke, Joerg, Fischer, Barbara, Barbin, Karin, Schreiter, Katja, Wachter, Yvonne, Mahr, Kerstin, Titgemeyer, Fritz, Niederweis, Michael, Peipp, Matthias, Zunino, Susan J., Repp, Roland, Valerius, Thomas, and Fey, Georg H.
- Subjects
- *
RECOMBINANT antibodies , *HLA histocompatibility antigens , *LYMPHOMAS , *CANCER cells , *GENE expression , *CHROMATOGRAPHIC analysis - Abstract
Bispecific antibodies offer the possibility of improving effector-cell recruitment for antibody therapy. For this purpose, a recombinant bispecific single-chain Fv antibody (bsscFv), directed against Fc γRIII (CD16) and human leucocyte antigen (HLA) class II, was constructed and tested in functional assays. RNA from the hybridomas 3G8 and F3.3, reacting with CD16 and HLA class II, respectively, was used to generate phage display libraries. From these libraries, reactive phages were isolated and the bsscFv was constructed by connecting both single-chain Fv components through a 20 amino acid flexible linker. After expression in SF21 insect cells and chromatographic purification, the bsscFv bound specifically and simultaneously to both antigens. The affinities of the anti-CD16 and the anti-HLA class II scFv components of the bsscFv were 8·6 × 10−8 mol/l and 13·7 × 10−8 mol/l, respectively, which was approximately sevenfold lower than the F(ab) fragments of the parental antibodies. In antibody-dependent cellular cytotoxicity experiments with human mononuclear cells as effectors, the bsscFv-mediated specific lysis of both HLA class II-positive, malignant human B-lymphoid cell lines and primary cells from patients with chronic B-cell lymphocytic leukaemia. Optimal lysis was obtained at bsscFv concentrations of approximately 400 ng/ml, similar to the concentration required for maximum lysis by the corresponding chemically linked bispecific antibody. Thus, this recombinant bsscFv-antibody is an efficient molecule for effector-cell mediated lysis of malignant human B-lymphoid cells. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
46. research paper Ex vivo analysis of aberrant splicing induced by two donor site mutations in PKLR of a patient with severe pyruvate kinase deficiency.
- Author
-
van Wijk, Richard, van Wesel, Annet C. W., Thomas, Adri A. M., Rijksen, Gert, and van Solinge, Wouter W.
- Subjects
- *
PYRUVATE kinase , *NUCLEOTIDES , *GENETIC mutation , *ANEMIA , *INTRONS , *EXONS (Genetics) , *MESSENGER RNA - Abstract
Two single-nucleotide substitutions in PKLR constituted the molecular basis underlying pyruvate kinase (PK) deficiency in a patient with severe haemolytic anaemia. One novel mutation, IVS5+1G>A, abolished the intron 5 donor splice site. The other mutation, c.1436G>A, altered the intron 10 donor splice site consensus sequence and, moreover, encoded an R479H substitution. We studied the effects on PKLR pre-mRNA processing, using ex vivo-produced nucleated erythroid cells from the patient. Abolition of the intron 5 splice site initiated two events in the majority of transcripts: skipping of exon 5 or, surprisingly, simultaneous skipping of exon 5 and 6 (Δ5,6). Subcellular localization of transcripts suggested that no functional protein was produced by the IVS5+1A allele. The unusual Δ5,6 transcript suggests that efficient inclusion of exon 6 in wild-type PKLR mRNA depends on the presence of splice-enhancing elements in exon 5. The c.1436G>A mutation caused skipping of exon 10 but was mainly associated with a severe reduction in transcripts although these were, in general, normally processed. Accordingly, low amounts of PK were detected in nucleated erythroid cells of the patient, thus correlating with the patient's PK-deficient phenotype. Finally, several low-abundant transcripts were detected that represent the first examples of ‘leaky-splicing’ in PKLR. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
47. research paper Haematopoietic stem cell transplantation with non-myeloablative conditioning in the outpatient setting: results, complications and admission requirements in a single institution.
- Author
-
Petersen, Søren L., Madsen, Hans O., Ryder, Lars P., Svejgaard, Arne, Jakobsen, Bodil K., Sengeløv, Henrik, Heilmann, Carsten, Dickmeiss, Ebbe, and Vindeløv, Lars L.
- Subjects
- *
BLOOD diseases , *STEM cells , *GRAFT versus host disease , *TRANSPLANTATION of organs, tissues, etc. , *LEUCOCYTES , *FLUDARABINE , *ANTIGENS - Abstract
Thirty patients with haematological malignancies received peripheral blood stem cells from human leucocyte antigen (HLA)-identical sibling donors after non-myeloablative conditioning with fludarabine and total body irradiation. Twenty-seven patients received the transplant as an outpatient procedure. All patients engrafted. The probability of acute graft- versus-host disease (GVHD) grades II–IV and extensive chronic GVHD was 57% and 80%, respectively. Patients alive on day +365 experienced a median of 44 d (range 4–151) of hospitalization during the first year. In the entire cohort, GVHD accounted for 22%, infections for 18%, thrombotic thrombocytopenic purpura (TTP) for 16% and engraftment syndrome for 14% of the time in hospital. The 1-year risk of TTP was 26%. Acute GVHD was a risk factor for the development of TTP ( P = 0·008). With a median follow-up of 602 d, the 2-year estimates for overall survival, progression-free survival, non-relapse mortality and relapse related mortality were 68%, 43%, 22% and 13%, respectively. This transplantation regimen is feasible and induces long-term remissions in heavily pretreated patients. The procedure can be performed in the outpatient setting, but complications could result in a substantial number of admissions during the first year. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
48. research paper Results of imatinib mesylate therapy in chronic myelogenous leukaemia with variant Philadelphia chromosome.
- Author
-
El-Zimaity, Maha M. T., Kantarjian, Hagop, Talpaz, Moshe, O'Brien, Susan, Giles, Francis, Garcia-Manero, Guillermo, Verstovsek, Srdan, Thomas, Deborah, Ferrajoli, Alessandra, Hayes, Kimberly, Bekele, B. Nebiyou, Zhou, Xian, Rios, Mary B., Glassman, Armand B., and Cortes, Jorge E.
- Subjects
- *
MYELOID leukemia , *LEUKEMIA treatment , *IMATINIB , *METHANESULFONATES , *CHROMOSOMES , *CHROMOSOMAL translocation , *CANCER patients - Abstract
Five to 10 per cent of patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukaemia (CML) have variant translocations involving chromosomes other than 9 and 22. We investigated the characteristics and outcome of patients with variant translocations treated with imatinib. Among 721 patients, 44 (6%) had variant translocations, involving one ( n = 39) or two ( n = 4) additional chromosomes. Nineteen patients (44%) were in chronic (12 previously untreated), 24 (55%) in accelerated and one (2%) in blastic phase. A major cytogenetic response was achieved in 14 (74%) patients treated in chronic phase and in 14 (58%) treated in accelerated phase. Six of 13 (46%) evaluable patients had deletion of derivative chromosome 9, and there was a trend for a lower response rate in these patients. We compared the 43 patients in chronic or accelerated phase to 678 patients with classic Ph treated with imatinib. The only significant difference in clinical characteristics was a higher frequency of accelerated phase among those with variant translocations (56%) compared with those with classic translocations (38%). No differences in outcome were evident. In a multivariate analysis, variant Ph translocations had no impact in response rate, overall survival or duration of response. We conclude that patients with variant Ph translocations have a similar prognosis to those with classic Ph translocations when treated with imatinib. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
49. research paper CD21S antigen expression in tumour cells of diffuse large B-cell lymphomas is an independent prognostic factor indicating better overall survival.
- Author
-
Ogawa, Shoko, Yamaguchi, Motoko, Oka, Kouji, Taniguchi, Masanori, Ito, Motohiro, Nishii, Kazuhiro, Nakase, Kazunori, Ohno, Toshiyuki, Kita, Kenkichi, Kobayashi, Tohru, and Shiku, Hiroshi
- Subjects
- *
CD antigens , *B cell lymphoma , *CANCER cells , *IMMUNOPHENOTYPING , *IMMUNOHISTOCHEMISTRY techniques , *ONCOLOGY - Abstract
To evaluate the clinical significance of CD21S expression of diffuse large B-cell lymphoma (DLBCL) tumour cells, we compared their clinical features, immunophenotype, response to therapy and outcome in relation to CD21S expression. Between 1987 and 1999, frozen sections from 240 DLBCL cases were examined for CD21S expression by immunohistochemical methods. CD21S expression was detected on the tumour cells of 87 (36%) cases. The median age of the CD21S+ DLBCL cases was 65 years (range: 17–84 years), the male–female ratio was 42:45, and they showed the following clinical features: Eastern Cooperative Oncology Group score >1 in 14%, lactate dehydrogenase greater than normal levels in 38%, extranodal sites >1 in 14%, stages III/IV disease at diagnosis in 29%, B symptoms in 17%, and a high/high–intermediate International Prognostic Index (IPI) in 23%. They also showed a better overall survival ( P = 0·00001, log-rank test) and a better complete remission rate ( P = 0·00004, chi-square test) than CD21S− DLBCL. Moreover, CD21S+ DLBCL showed a better survival than CD21S− DLBCL for both low/low–intermediate and high/high–intermediate risk categories of IPI ( P = 0·045 and P = 0·0016 respectively). Multivariate analysis identified CD21S expression as an independent factor for survival when compared with the five IPI factors. These findings indicate that CD21S expression of DLBCL tumour cells is a useful prognostic factor for survival. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
50. research paper Expression of cyclin E in resting and activated B-chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target.
- Author
-
Decker, Thomas, Hipp, Susanne, Hahntow, Ines, Schneller, Folker, and Peschel, Christian
- Subjects
- *
LYMPHOCYTIC leukemia , *CYCLIN-dependent kinases , *B cells , *LEUKEMIA , *CELL proliferation , *CELL death - Abstract
Disease progression in B-cell chronic lymphocytic leukaemia (B-CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B-CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B-CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin-dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B-CLL cells. Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B-CLL. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.