| 1. |
- Lönnerholm, Gudmar, et al.
(författare)
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In vitro cellular drug sensitivity at diagnosis is correlated to minimal residual disease at end of induction therapy in childhood acute lymphoblastic leukemia.
- 2009
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Ingår i: Leukemia research. - Oxford : Elsevier BV. - 0145-2126 .- 1873-5835. ; 33:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic cells from 85 children with newly diagnosed precursor B-lineage ALL were tested for in vitro drug sensitivity to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. There was a significant correlation between MRD day 29 and in vitro sensitivity to prednisolone (p<0.001) and doxorubicin (p=0.017), drugs administered during induction therapy. In patients with t(12;21) (n=20), in vitro sensitivity to doxorubicin was an independent factor for MRD <0.1% (p=0.031; R(2)=0.66). Thus, data show that in vitro drug sensitivity at diagnosis is correlated to cell kill during induction therapy as measured by MRD day 29.
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| 2. |
- Thörnerup, Ingrid, et al.
(författare)
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Minimal residual disease assessment in childhood acute lymphoblastic leukaemia: a Swedish multi-centre study comparing real-time polymerase chain reaction and multicolour flow cytometry.
- 2011
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 152:6, s. 743-753
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) assessment is a powerful prognostic factor for determining the risk of relapse in childhood acute lymphoblastic leukaemia (ALL). In this Swedish multi-centre study of childhood ALL diagnosed between 2002 and 2006, the MRD levels were analysed in 726 follow-up samples in 228 children using real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes and multicolour flow cytometry (FCM). Using an MRD threshold of 0·1%, which was the sensitivity level reached in all analyses, the concordance between RQ-PCR and FCM MRD values at day 29 was 84%. In B-cell precursor ALL, an MRD level of ≥0·1% at day 29 predicted a higher risk of bone marrow relapse (BMR) with both methods, although FCM was a better discriminator. However, considering the higher median MRD values achieved with RQ-PCR, a higher MRD cut-off (≥0·2%) improved the predictive capacity of RQ-PCR. In T-ALL, RQ-PCR was notably superior to FCM in predicting risk of BMR. That notwithstanding, MRD levels of ≥0·1%, detected by either method at day 29, could not predict isolated extramedullary relapse. In conclusion, the concordance between RQ-PCR and FCM was high and hence both methods are valuable clinical tools for identifying childhood ALL cases with increased risk of BMR.
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| 3. |
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| 4. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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A transforming growth factor-beta1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura.
- 2000
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Ingår i: Annals of hematology. - 0939-5555. ; 79:9, s. 507-13
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Tidskriftsartikel (refereegranskat)abstract
- Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-beta1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) < 50 x 10(9)/l, (2) 50-150 x 10(9)/l and (3) > 150 x 10(9)/l. We found significantly elevated plasma levels of the Th3 cytokine TGF-beta1 in patients with pltc >150x10(9)/l (23.5+/-2.8ng/ml), compared with patients with pltc <50x10(9)/l (2.3+/-0.6 ng/ml; P<0.0001), patients with pltc 50-150x 10(9)/l (7.2+/-1.7 ng/ml; P<0.0001) and healthy volunteers (9.8+/-1.3 ng/ml; P<0.01). The serum levels of the Thl cytokines interleukin (IL)-2 and interferon (IFN)-y were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc <50 x 10(9)/l had significantly lower levels (0.6+/-0.1 pg/ml) than both patients with pltc 50-150 x 10(9)/l (1.8 +/- 0.1 pg/ml; P<0.005) and healthy volunteers (1.4+/-0.1 pg/ml; P<0.005). Furthermore, patients with pltc <50 x 10(9)/l and splenectomised patients had significantly higher levels of CD4 + CD25 + activated T cells [26.2 +/- 14.8% (P<0.05) and 26.7+/-11.9% (P<0.005), respectively] than healthy controls (16.5+/-4.0%). Also, the number of natural killer (NK) cells among patients with pltc >150 x 10(9)/l were significantly elevated (26.6+/-16.0%; P<0.05) compared with controls (17.4+/-7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-beta1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-beta1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease.
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| 5. |
- Andreasson, Björn, et al.
(författare)
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The measurement of venous haematocrit in patients with polycythaemia vera.
- 1999
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 246:3, s. 293-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In clinical practice, patients with polycythaemia vera (PV) are monitored by measurement of venous packed cell volume (PCV). However, whereas treatment recommendations are still based upon studies in which the results were obtained with the centrifuged microhaematocrit, currently in most instances automated blood cell counters are used to calculate PCV. In a group of patients with polycythaemia we therefore compared the results obtained by the microhaematocrit method with PCV calculated by haematology analysers. DESIGN: The study was carried out on a prospective basis. Duplicate venous blood samples were collected. The centrifuged microhaemotocrit was obtained by using an IEC Micro-MB Centrifuge. Depending on different routine methods used in the participating hospitals, the blood cell counter PCV was calculated using Coulter STKS, Bayer Technicon H2 or H3. SETTING: Patients were included from four Swedish university hospitals: Akademiska (Uppsala), Huddinge and Karolinska (Stockholm) and Sahlgrenska (Göteborg). SUBJECTS: Seventy-four patients with PV and 10 patients with secondary polycythaemia were included and a total of 150 duplicate blood samples were analysed from these subjects. RESULTS: In the 150 measurements the mean blood cell counter calculated PCV was 0.448 +/- 0.037; the mean for centrifuged microhaematocrit was 0.467 +/- 0. 037 and the difference between means was highly significant (P = 6.8 x 10-25). The means for centrifuged haematocrit and calculated PCV differed significantly in the groups of PV patients treated with phlebotomy only, hydroxyurea or radiophosphorous (P < 0.0001, respectively). In PV patients treated with alpha-interferon and in patients with secondary polycythaemia the difference in means did not reach statistical significance (P = 0.07 and P = 0.13, respectively). The groups of patients with MCV <80 fL and >/=80 fL both presented significant differences between means for calculated PCV and centrifuged haematocrit. CONCLUSIONS: If PV patients are monitored with blood cell counter calculated PCV it appears that the therapeutic goal should be to maintain the calculated PCV below 0.43, provided the local differences in calculated PCV and centrifuged haematocrit are of the same magnitude as in this study.
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| 6. |
- Björklund, Elisabet, et al.
(författare)
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Quality control of flow cytometry data analysis for evaluation of minimal residual disease in bone marrow from acute leukemia patients during treatment.
- 2009
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Ingår i: Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. - : Lippincott Williams & Wilkins. - 1536-3678 .- 1077-4114. ; 31:6, s. 406-15
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Tidskriftsartikel (refereegranskat)abstract
- Low levels of leukemia cells in the bone marrow, minimal residual disease (MRD), are considered to be a powerful indicator of treatment response in acute lymphatic leukemia (ALL). A Nordic quality assurance program, aimed on standardization of the flow cytometry MRD analysis, has been established before implementation of MRD at cutoff level 10 as one of stratifying parameters in next Nordic Society of Pediatric Hematology and Oncology (NOPHO) treatment program for ALL. In 4 quality control (QC) rounds 15 laboratories determined the MRD levels in 48 follow-up samples from 12 ALL patients treated according to NOPHO 2000. Analysis procedures were standardized. For each QC round a compact disc containing data in list-mode files was sent out and results were submitted to a central laboratory. At cutoff level 10, which will be applied for clinical decisions, laboratories obtained a high concordance (91.6%). If cutoff level 10 was applied, the concordance would be lower (85.3%). The continuing standardization resulted in better concordance in QC3 and QC4 compared with QC1 and QC2. The concordance was higher in precursor B as compared with T-cell ALL. We conclude that after standardization, flow cytometry MRD detection can be reliably applied in international, multicenter treatment protocols.
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| 7. |
- Boman, Hans, 1955, et al.
(författare)
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Newly diagnosed bladder cancer: the relationship of initial symptoms, degree of microhematuria and tumor marker status.
- 2002
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Ingår i: The Journal of urology. - 0022-5347. ; 168:5, s. 1955-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We recorded initial symptoms and evaluated the frequency and intensity of hematuria in patients with newly diagnosed bladder cancer. We also evaluated and compared the sensitivity of bladder wash cytology, NMP22 (Matritech, Newton, Massachusetts), BTA Stat (Bion Diagnostic Sciences, Redmond, Washington) and UBC antigen (IDL Biotech, Sollentona, Sweden) with hematuria dipsticks and flow cytometry for determining the size of erythrocytes in urine. MATERIALS AND METHODS: Urine samples were collected from 92 patients with newly diagnosed bladder cancer, 64 with idiopathic microhematuria and 42 with nephritis. Urine was analyzed for NMP22, BTA Stat, UBC and erythrocytes size using flow cytometry. Bladder wash cytology was done at cystoscopy. Urine was analyzed for microhematuria with hematuria dipsticks at home for 7 consecutive days immediately before the operation and in the hospital on the day of surgery. RESULTS: Sensitivity was 75% for NMP22, 78% for BTA Stat, 64% for UBC and 61% for flow cytometry at 73% specificity. Cytology had 42% sensitivity at 97% specificity. Tumor size, grade and stage had a statistically significant influence on NMP22, BTA Stat, UBC and cytology. Of the patients 75% had microhematuria on the day of the operation and 75% had hematuria at least 1 of 7 days when tested at home the last week before transurethral bladder resection. The 70% of all patients with macroscopic hematuria as the initial symptom did not seem to differ from those without the condition in tumor size, grade, stage or tumor marker levels. CONCLUSIONS: Flow cytometry was not well enough able to distinguish patients with bladder cancer from controls. The sensitivity of all tested markers, including hematuria dipsticks, was high for large and high grade, high stage tumors. Further studies are needed to evaluate whether a marker could be used to determine priority among patients referred due to microhematuria.
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| 8. |
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| 9. |
- Forsberg, B, et al.
(författare)
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The platelet-specific alloantigen PlA1 (HPA-1a): a comparison of flow cytometric immunophenotyping and genotyping using polymerase chain reaction and restriction fragment length polymorphism in a Swedish blood donor population.
- 1995
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Ingår i: Transfusion. - 0041-1132. ; 35:3, s. 241-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is an increasing interest in the development of rapid and reliable techniques for platelet alloantigen typing. STUDY DESIGN AND METHODS: By use of standardized flow cytometry and a specific human alloantiserum, 236 Swedish blood donors were immunophenotyped for the platelet-specific alloantigen, PlA1 (HPA-1a). RESULTS: Ten individuals (4.2%) had low fluorescence intensities and were considered PlA1-negative (HPA-1a-negative); all of them also demonstrated a PlA2/PlA2 (HPA-1b/1b) genotype in a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay of the underlying DNA polymorphism. The remaining population had clear positive fluorescence and was regarded as PlA1-positive (HPA-1a-positive). The fluorescence distribution histogram among PlA1-positive (HPA-1a-positive) individuals was dome-shaped, and those individuals who were homozygous for PlA1 (HPA-1a) could not be distinguished from those who were heterozygous. This finding was further substantiated by PCR-RFLP analysis of the PlA1/PlA2 (HPA-1a/1b) genotype; a heterozygous genotype was found among those having a medium fluorescence intensity as well as among those having a strong fluorescence intensity. CONCLUSION: Flow cytometry is a valuable tool for large-scale detection of PlA1 (HPA-1a). However, flow cytometry based on only one antiserum cannot distinguish between homozygous and heterozygous carriers of PlA1 (HPA-1a). For zygosity testing and when platelets are difficult to obtain, the PCR-RFLP technique is the assay of choice.
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| 10. |
- Grund, Sofia, et al.
(författare)
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CD69 is a good surrogate marker for IgVH gene mutation status in Swedish chronic lymphocytic leukemia (CLL) patients.
- 2010
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Ingår i: Acta Haematologica Polonica. - 0001-5814. ; 41:1, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) patients with unmutated IgVH genes have poorer survival than patients with mutated IgVH genes. However, mutation analysis is not always available in the routine laboratory and therefore surrogate markers are needed. CD69 has in two previous studies been shown to be a marker for mutation status. Our aim was therefore to investigate if CD69 expression was a better marker for mutation status than ZAP-70 and CD38 in a sample of patients from the west of Sweden. We analyzed the expression of CD69 in CD19+ B cells from CLL patients and controls using flow cytometry. CD69 was higher expressed in B cells from CLL patients compared with controls (35±31% and 2.6±1.8% CD19+/CD69+ cells respectively, P=0.0010). Patients with unmutated IgVH genes had a higher percentage of CD19+/CD69+ cells compared with patients with mutated IgVH genes (70±24% vs. 18±12%, P=0.00076). Furthermore, there was a strong concordance, even better than for CD38 and ZAP-70, between expression of CD69 and IgVH mutation status (96%, P<0.0001). Thus, our data in combination with those from others indicate that CD69 may be an excellent surrogate marker for IgVH mutation status and ultimately survival. Furthermore, this analysis is well suited for routine analysis.
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