| 11. |
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| 12. |
- Goldin, Lynn R., et al.
(författare)
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Highly increased familial risks for specific lymphoma subtypes
- 2009
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 146:1, s. 91-94
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Tidskriftsartikel (refereegranskat)abstract
- P>Studies have shown that familial risk contributes to aetiology of lymphomas. Using large population registries from Sweden, we evaluated risk of lymphoma subtypes among first-degree relatives of 2668 follicular lymphoma (FL) patients, 2517 diffuse large B-cell lymphoma (DLBCL) patients, and 6963 Hodgkin lymphoma (HL) patients compared to first-degree relatives of controls. Relatives were at the highest risk for developing the same lymphoma subtype as the case. DLBCL was increased 10-fold among relatives of DLBCL patients, FL was increased fourfold among relatives of FL patients and HL was increased fourfold among relatives of HL patients. These results imply that germline susceptibility genes are specific to lymphoma subtype.
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| 13. |
- Grövdal, Michael, et al.
(författare)
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Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy
- 2010
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:3, s. 293-302
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Tidskriftsartikel (refereegranskat)abstract
- This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.
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| 14. |
- Hellstrom-Lindberg, E., et al.
(författare)
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A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor : Significant effects on quality of life
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 120, s. 1037-
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Tidskriftsartikel (refereegranskat)abstract
- We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S-Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony-stimulating factor (G-CSF) + Epo. S-Epo = 500 U/l and a transfusion need of < 2 units/month predicted a high probability of response to treatment, S-Epo > 500 U/l and =2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G-CSF + Epo. The overall response rate was 42% with 28.3% achieving a complete and 13.2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0.001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0.01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48-74%) to treatment with G-CSF + Epo. The majority of these patients have shown complete and durable responses.
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| 15. |
- Irshaid, N M, et al.
(författare)
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Genomic typing of the Kidd blood group locus by a single-tube allele-specific primer PCR technique
- 1998
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 102:4, s. 1010-1014
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Tidskriftsartikel (refereegranskat)abstract
- The Kidd (JK) blood group system is clinically important in transfusion medicine. Alloantibodies to antigens in this system may be produced following blood transfusion or during pregnancy and can result in serious haemolytic transfusion reactions and haemolytic disease of the newborn (HDN). JK antigens on erythrocytes are carried by glycoproteins with the capacity to transport urea through cell membranes. cDNA complementary to mRNA transcribed at the JK locus was cloned in 1994. The molecular basis of the Jk(a)/Jk(b) blood group polymorphism was recently shown to be a single nucleotide substitution predicting an amino acid change (Asp280Asn) in an extracellular loop of the JK glycoprotein. After confirmation of the JK gene polymorphism we developed a rapid and robust technique for JK genotyping with allele-specific primers in a single-tube PCR. In addition, a 217 bp intron located at nucleotides 811-812 in the JK gene was found and sequenced. The genotyping test was validated with samples from 106 Caucasian Swedish and 13 Black South African random blood donors. Complete phenotype-genotype correlations were obtained. However, four Jk(a-b-) samples of Polynesian and Finnish origin typed as Jk(b)Jk(b). Potential use of the presented method can be predicted in clinical transfusion medicine including prenatal determination of the JK genotype in a fetus at risk for HDN caused by JK antibodies.
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| 16. |
- Juliusson, Gunnar, et al.
(författare)
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Increased remissions from one course for intermediate-dose cytosine arabinoside and idarubicin in elderly acute myeloid leukaemia when combined with cladribine. A randomized population-based phase II study
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 123:5, s. 810-818
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Tidskriftsartikel (refereegranskat)abstract
- Cladribine has single-drug activity in acute myeloid leukaemia (AML), and may enhance the formation of the active metabolite (ara-CTP) of cytosine arabinoside (ara-C). To evaluate the feasibility of adding intermittent cladribine to intermediate-dose ara-C (1 g/m(2)/2 h) b.i.d. for 4 d with idarubicin (CCI), we performed a 2:1 randomized phase II trial in AML patients aged over 60 years. Primary endpoints were time to recovery from cytopenia and need for supportive care following the first course. Sixty-three patients (median 71 years, range 60-84 years) were included, constituting 72% of all eligible patients. Toxicity was limited, with no differences between the treatment arms. The early toxic death rate was 11%. The median time to recovery from neutropenia and thrombocytopenia was 22 and 17 d from the start of course no. 1, respectively, and the requirement for platelet and red cell transfusions was four and eight units respectively. Patients had a median of 8 d with fever over 38degreesC, and 17 d with intravenous antibiotic treatment. The overall complete remission (CR) rate was 62%, with 51% CR from one course of CCI in comparison with 35% for the two-drug therapy (P = 0.014). The median survival with a 2-year follow-up was 14 months, and the 2-year survival was over 30%, with no differences between the treatment arms. Considering the median age and our population-based approach, the overall results are encouraging.
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| 17. |
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| 18. |
- Karrman, Kristina, et al.
(författare)
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The t(X;7)(q22;q34) in paediatric T-cell acute lymphoblastic leukaemia results in overexpression of the insulin receptor substrate 4 gene through illegitimate recombination with the T-cell receptor beta locus.
- 2009
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 144, s. 546-551
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Tidskriftsartikel (refereegranskat)abstract
- Summary The t(X;7)(q22;q34), a translocation not previously reported in a neoplastic disorder, was identified and molecularly characterised in a paediatric T-cell acute lymphoblastic leukaemia (T-ALL), subsequently shown also to harbour a deletion of 6q, a STIL/TAL1 fusion and an activating NOTCH1 mutation. The t(X;7) was further investigated using fluorescence in situ hybridisation (FISH), real-time quantitative polymerase chain reaction (RQ-PCR) and Western blot analyses. FISH revealed a breakpoint at the T-cell receptor beta locus at 7q34 and mapped the corresponding breakpoint to Xq22.3. The latter region contains only two known genes, namely insulin receptor substrate 4 (IRS4) and collagen, type IV, alpha 5 (COL4A5), the expressions of which were analysed by the use of RQ-PCR. COL4A5 was not differentially expressed in the t(X;7)-positive sample compared to five T-ALL controls. However, a marked, 1000-fold overexpression of IRS4 was identified. Western blot analysis with a monoclonal antibody against IRS4 showed overexpression also at the protein level. Considering that forced expression of several members of the IRS family has been shown to result in increased cell proliferation, for example in haematopoietic cells, we hypothesise that the IRS4 up-regulation in T-ALL is pathogenetically important as a mitogenic stimulus.
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| 19. |
- Kuchinskaya, Ekaterina, et al.
(författare)
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Array-CGH reveals hidden gene dose changes in children with acute lymphoblastic leukaemia and a normal or failed karyotype by G-banding
- 2008
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 140:5, s. 572-577
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Tidskriftsartikel (refereegranskat)abstract
- A tiling path 33K BAC array was used to study 28 children with acute lymphoblastic leukaemia (ALL) who had normal or failed G-banded karyotypes. Twenty-two patients (79%) had a total of 135 copy number alterations (CNA) (69 gains and 66 losses); most of these patients showed CNA that were below the resolution of G-banding. Molecular cytogenetic and array comparative genomic hybridization results enabled the division of B-precursor ALL patients into five groups: high hyperdiploidy, intrachromosomal amplification of 21q, ETV6/RUNX1 rearrangement, others and no CNA. Apart from a shared deletion of 9p21.3, T-ALL patients had additional small CNA, with no region in common.
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| 20. |
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