| 1. |
- Geisler, Christian H., et al.
(författare)
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Nordic MCL2 trial update : six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC plus autologous stem-cell support: still very long survival but late relapses do occur
- 2012
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 158:3, s. 355-362
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early based on the median observation time of 4 years results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6.5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7.4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL.
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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. |
- Baecklund, Eva, et al.
(författare)
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Expression of the human germinal-centre-associated lymphoma protein in diffuse large B-cell lymphomas in patients with rheumatoid arthritis
- 2008
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 141:1, s. 69-72
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B-cell lymphomas (DLBCL) can be subdivided into germinal centre (GC)-like and non-GC-like subtypes by CD10, BCL6 and MUM1/IRF4 status. We previously reported that patients with severe rheumatoid arthritis (RA) are at increased risk of non-GC DLBCL. This study examined a new GC-marker, human germinal-centre-associated lymphoma (HGAL) protein, in RA-DLBCL. Of 111, 38 (34%) DLBCL were HGAL-positive and showed less disseminated disease and a tendency toward improved overall survival compared to HGAL-negative cases. This supports that a majority of RA-DLBCL are of non-GC origin, indicating a specific role for activated peripheral B cells in the pathogenesis of RA-DLBCL.
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| 4. |
- Christiansen, Ilse, et al.
(författare)
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Elevated serum levels of soluble vascular cell adhesion molecule-1(sVCAM-1) closely reflect tumour burden in chronic B-lymphocytic leukaemia
- 1998
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 103:4, s. 1129-1137
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Tidskriftsartikel (refereegranskat)abstract
- The present study is the first to report elevated serum levels of soluble (s)VCAM-1 in B-cell chronic lymphocytic leukaemia (B-CLL). A large cohort of 106 untreated patients was studied. sVCAM-1 was compared to known prognostic serum markers (soluble (s)ICAM-1; lactate dehydrogenase, LDH; sCD23; thymidine kinase, TK; beta2microglobulin, beta2m). The serum levels of sVCAM-1 reflected tumour burden as expressed by Binet/Rai stages more closely than any other marker. sVCAM-1 also reflected the kinetics of the disease as revealed by lymphocyte doubling time. sVCAM-1 was the only one of the studied markers which showed elevated levels in smouldering disease compared to controls. sVCAM-1, sICAM-1 and sCD23 (but not LDH, TK, beta2m) separated smouldering from non-smouldering B-CLL. Only sICAM-1, sCD23 and TK added independent prognostic information for survival to that of stage and lymphocyte doubling time. The expression of both adhesion molecules was examined in lymph node and splenic specimens. VCAM-1 and ICAM-1 were overexpressed by vascular endothelium and stroma, but the intensity of expression correlated poorly with serum levels of the soluble molecules. In conclusion, serum levels of sVCAM-1 correlated with tumour burden and other prognostic markers in B-CLL. VCAM-1 was overexpressed in tumour tissue as was ICAM-1. sVCAM-1 could prove a valuable marker in younger early-stage patients eligible for therapeutic trials.
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| 5. |
- Hedström, Gustaf, et al.
(författare)
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Mast cell infiltration is a favourable prognostic factor in diffuse large B-cell lymphoma
- 2007
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 138:1, s. 68-71
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies indicate that the inflammatory response in diffuse large B-cell lymphomas (DLBCL) is important for the clinical outcome. Mast cells are key regulators in this response; we investigated whether the number of tryptase-positive mast cells is correlated with clinical outcome. Patients with many mast cells had a significantly better event-free survival (EFS) compared to those with few mast cells (P < 0.03 in both germinal centre (GC) and non-GC DLBCL. This supports the idea that the infiltration of mast cells is a reflection of the host inflammatory response and is related to a favourable outcome.
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| 6. |
- Molin, Daniel, et al.
(författare)
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Mast cell infiltration correlates with poor prognosis in Hodgkin's lymphoma
- 2002
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 119:1, s. 122-124
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Tidskriftsartikel (refereegranskat)abstract
- Hodgkin's lymphoma (HL) is characterized by a few Hodgkin, Reed-Sternberg cells (HRS) surrounded by benign cells. We recently reported that mast cells were the predominant CD30L-positive cells in HL tumours, and that they activate HRS in vitro through CD30L-CD30 interaction. Here, we investigated the clinical importance of mast cell infiltration in the tumours of 123 patients. Tumour specimens were stained with a mast-cell-specific antibody that detects tryptase. Mast cells were detected in virtually every case and increasing numbers of mast cells correlated to nodular sclerosis histology (P = 0.008). Patients with higher mast cell infiltration had a worse relapse-free survival (P = 0.01).
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| 7. |
- Molin, Daniel, et al.
(författare)
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Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease
- 2001
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 114:3, s. 616-623
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Tidskriftsartikel (refereegranskat)abstract
- Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.
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| 8. |
- Norén-Nyström, Ulrika, et al.
(författare)
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Vascular density in childhood acute lymphoblastic leukaemia correlates to biological factors and outcome
- 2009
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 146:5, s. 521-530
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Tidskriftsartikel (refereegranskat)abstract
- The issue of angiogenesis and its clinical relevance in childhood acute lymphoblastic leukaemia (ALL) is controversial. In the present study, microvessel density (MVD), analysed in 185 diagnostic bone marrow biopsies, was higher in T-cell ALL compared to B-cell precursor (BCP)-ALL (P = 0.013). In the BCP group, cases with t(12;21) were characterized by a low MVD while patients with high-hyperdiploid leukaemia (HeH, 51-61 chromosomes) showed a high MVD compared to other BCP patients (P = 0.001 and 0.002 respectively). There was a correlation between MVD and white blood cell (WBC) count in high-risk BCP patients (P = 0.021). In addition, BCP patients with a high marrow reticulin fibre density and high MVD had an unfavourable outcome compared to the other BCP patients (P = 0.002). The fraction of vessels in which lumina were filled with blasts (blast congested vessel fraction) correlated strongly with WBC count (P < 0.001). These findings indicate that the angiogenic process interacts with other stroma-factors, such as reticulin fibre density, in its effect on outcome, and is coupled to both the ALL genotype and phenotype. One possible implication is that different subtypes of childhood ALL may respond differently to anti-angiogenic drugs as a supplement in first-line treatment.
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| 9. |
- Wahlin, Bjorn E., et al.
(författare)
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Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times
- 2012
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 156:2, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population-based cohort of 505 patients with a median follow-up time of 10.0 years (range, 4.616.0). After excluding 43 patients with concomitant diffuse large B-cell lymphoma, 345 remained with grade 12, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 12 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 13A and independently of clinical factors, grade 3B correlated with higher mortality (P = 0.008), but outcome was improved after upfront anthracycline-containing therapy (P = 0.015). In contrast to grade 13A patients, grade 3B patients experienced no relapses or deaths beyond 5 years of follow-up. Furthermore, patients with grade 3B were predominantly male and seldom presented with bone-marrow involvement. We conclude that follicular lymphoma grade 13A is indolent and incurable with conventional therapy. Grade 3B appears to be an aggressive but curable disease.
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| 10. |
- Christiansen, Ilse, et al.
(författare)
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Soluble vascular cell adhesion molecule-1 (sVCAM-1) is an independent prognostic marker in Hodgkin's disease
- 1998
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 102:3, s. 701-9
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Tidskriftsartikel (refereegranskat)abstract
- Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1. sCD106) were significantly elevated in patients with Hodgkin's disease (HD) (n = 101) compared to controls (n= 31) (P<0.0001). sVCAM-1 correlated with histology, stage, B-symptoms, and prognostic markers (sICAM-1, sCD30, sIL-2R, LDH). sVCAM-1, sICAM-1 and sCD30 added independent prognostic information for both disease-free and overall survival. 14 biopsies from 13 patients with HD were immunostained for VCAM-1 and ICAM-1. The vascular endothelium stained positive for VCAM-1 in 10/12 evaluable biopsies and for ICAM-1 in all evaluable biopsies. A stromal expression of both adhesion molecules precluded a precise evaluation of HRS-cells. This led us to investigate VCAM-1 (and ICAM-1) expression in six Hodgkin cell lines (HDLM-2, L428, L540, L591, DEV, KM-H2). Two cell lines stained positive for VCAM-1 (HDLM-2, L591). All cell lines stained positive for ICAM-1. sVCAM-1 is a new prognostic marker in HD; its predictive power equals or surpasses that of sCD30 and sICAM-1. Furthermore, two Hodgkin cell lines stained positive for VCAM-1. This indicates that VCAM-1 may be expressed by some HD tumour cells in vivo.
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