| 1. |
- Amini, Rose-Marie, et al.
(author)
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A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma
- 2002
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 68:4, s. 225-232
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Journal article (peer-reviewed)abstract
- Background: Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkin's lymphoma (HL). Patients and methods: In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995. Results: Fifty-eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved-field RT, and four after a short course of CT followed by extended-field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5-yr Hodgkin-specific survival (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis. Conclusions: Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.
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| 2. |
- Glimelius, Ingrid, 1975-, et al.
(author)
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Bulky disease is the most important prognostic factor in Hodgkin lymphoma stage IIB
- 2003
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 71:5, s. 327-33
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate treatment results for Hodgkin lymphoma (HL) patients younger than 60 yr in stage IIB, treated according to the Swedish National Care Programme. The intention was also to identify specific subgroups depending on the number of negative prognostic factors the patients have, in order to optimise and differentiate future treatment. In total, 99 patients with HL stage IIB, diagnosed between 1985 and 1994, have been analysed. There were 47 men and 52 women and the median age was 33 yr (range 17-59). Eighty-six patients presented with supradiaphragmatic disease and 13 with infradiaphragmatic. The HL specific and overall 10-yr survival was 73 and 65%, respectively. The HL-specific survival for patients in pathological stage IIB tended to be better, although not statistically significant than for clinical stage IIB, despite less chemotherapy (P = 0.1). The patients in stage IIB who were selected for laparotomy were, however, younger and with fewer negative prognostic factors. The only significant negative prognostic factor was bulky disease (P = 0.001). The following factors also tended to have a negative influence on the prognosis although not statistically significant: the International Prognostic Score, the number of involved lymph node stations, extranodal involvement and leucocyte count > 15 x 10(9)/L. In conclusion, we suggest that bulky disease should be taken into account when treating patients with stage IIB HL.
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| 3. |
- Amini, Rose-Marie, et al.
(author)
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Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience
- 2000
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 65:6, s. 379-389
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Journal article (peer-reviewed)abstract
- BACKGROUND: Despite improved treatment results achieved in Hodgkin's disease (HD), only about 70% of patients with advanced stages are cured. The primary aim of this study was to evaluate the outcome of advanced stages (IIB-IVB) of HD in younger patients in an unselected population-based group of patients. The patients were recommended individualized treatment with respect to number of chemotherapy (CT) courses and post-CT radiotherapy (RT) based on pretreatment characteristics and tumour response. Secondly, we investigated if variables of prognostic importance could be detected.PATIENTS AND METHODS: Between 1985-92, 307 patients between 17-59 yr of age (median 36) were diagnosed with HD in stages IIB-IVB in 5/6 health care regions in Sweden. Median follow-up time was 7.8 yr (1.3-13). Retrospectively, laboratory parameters were collected.RESULTS: In total, 267 (87%) patients had a complete response (CR). The overall and disease-free 10-yr survivals in the whole cohort were 76% and 67%, respectively. There was no difference in survival between the groups of patients who received 6 or 8 cycles of CT. Survival was not higher for patients in CR after CT when RT was added. For those in PR after CT, additional RT raised the frequencies of CR. A selected group of pathologically staged patients was successfully treated with a short course (2 cycles) of CT + RT. In univariate analyses survival was affected by age, stage IVB, bone-marrow involvement, B-symptoms, S-LDH, S-Alb and reaching CR or not after 2, 4 and 6 cycles of CT. In a multivariate analysis, age and reaching CR after 6 cycles of CT remained statistically significant.CONCLUSIONS: The lack of difference in survival between the groups of patients who received 6 versus 8 cycles of CT indicates a successful selection of patients for the shorter treatment. Reaching a rapid CR significantly affected outcome. Whether some patients need less CT than the generally recommended 8 courses can properly only be evaluated in a randomised study. Additional RT may play a role in successful outcome, particularly if residual tumours are present, but its precise role can also only be defined in prospectively randomised studies. Reaching CR after CT was the most important variable affecting survival besides age.
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| 4. |
- Glimelius, Ingrid, et al.
(author)
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IL-9 expression contributes to the cellular composition in Hodgkin lymphoma
- 2006
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 76:4, s. 278-283
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Journal article (peer-reviewed)abstract
- OBJECTIVES:The presence of numerous mast cells or eosinophils in Hodgkin lymphoma (HL) tumours have both been described as negative prognostic factors. One cytokine related to HL is interleukin-9 (IL-9) and it is known to affect both mast cells and eosinophils. The aim of this study was to explore if the expression of IL-9 correlates to the presence of these inflammatory cells in HL tumours.METHODS:In 131 HL biopsies, immunostainings for IL-9 and IL-9 receptor (IL-9R) were performed. The same material was previously stained for mast cells and eosinophils. These data were correlated to clinical and survival data from all patients.RESULTS:Fifty-three percent of cases were positive for IL-9 and 19% were positive for IL-9R in the cytoplasm of the tumour cells. The IL-9 positive patients had more eosinophils (P = 0.002) and mast cells (P = 0.02) in their tumours, more often a nodular sclerosis histology (P < 0.0001), a higher white-blood-cell count (P = 0.006) and a higher erythrocyte sedimentation rate (P = 0.003) at the time of diagnosis.CONCLUSIONS:IL-9 expression is related to the histology, clinical picture and the presence of eosinophils and mast cells in HL. These results indicate that IL-9 is an important part of the cytokine network and inflammatory infiltrate in HL.
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| 5. |
- Glimelius, Ingrid, 1975-, et al.
(author)
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Predictors of histology, tissue eosinophilia and mast cell infiltration in Hodgkin's Lymphoma : a population-based study
- 2011
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 87:3, s. 208-216
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Journal article (peer-reviewed)abstract
- Objective: Classical Hodgkin’s lymphoma (HL) lesions comprise few tumour cells, surrounded by numerous inflammatory cells. Like in other malignancies, the microenvironment is presumed to be clinically important in HL; however, microenvironment predictors remain poorly characterised. The aim of this study was to investigate how selected patient characteristics and genetic factors affect HL phenotype, in particular tissue eosinophilia, mast cell counts and HL histological subtype.Methods: In a population-based study, patients with HL were interviewed about potential HL risk factors. Available tumours, n = 448, were classified histologically; the number of eosinophils and mast cells were estimated, and eosinophil cationic protein (ECP) and eosinophil protein-x (EPX) gene polymorphisms were determined. Associations were assessed in regression models.Results: Self-reported history of asthma was predictive of having tumour eosinophilia [≥200 eosinophils/10 high power fields, univariate odds ratio (OR) = 2.22, 95% CI 1.06–4.64, P = 0.03]. High numbers of eosinophils were predominantly seen in patients carrying the genotype ECP434GG [multivariate relative levels (RLs) = 1.84, 95% CI 1.02–3.30, P = 0.04]. Lower number of eosinophils was seen in Epstein–Barr virus (EBV)-positive tumours (univariate RL = 0.52, 95% CI 0.3–0.9, P = 0.02) and in older patients (univariate RL = 0.85, 95% CI 0.73–0.99, P = 0.03). Well-known factors such as young age, female sex and EBV-negative status predicted nodular sclerosis histology.Conclusion: The number of eosinophils in HL tumours is influenced by patient traits such as asthma, ECP genotype and EBV status. EBV status was predictive of histology.
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| 6. |
- Delforoush, Maryam, 1980-, et al.
(author)
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Expression of possible targets for new proteasome inhibitors in diffuse large B-cell lymphoma
- 2017
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 98:1, s. 52-56
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Journal article (peer-reviewed)abstract
- Objectives: Investigating expression of possible targets for proteasome inhibitors in patients with diffuse large B-cell lymphoma (DLBCL) and correlating the findings to clinical parameters and outcome.Methods: Tumour material from 92 patients with DLBCL treated with either R-CHOP like (n = 69) or CHOP like (n = 23) regimens were stained for possible targets of proteasome inhibitors.Results: The primary target molecule of bortezomib, proteasome subunit beta, type 5 (PSMB5), was not detected in the tumour cells in any of the cases but showed an abundant expression in cells in the microenvironment. However, the deubiquitinases (DUBs) of the proteasome, the ubiquitin carboxyl-terminal hydrolase L5 (UCHL5) and the ubiquitin specific peptidase 14 (USP14), were detected in the cytoplasm of the tumour cells in 77% and 74% of the cases, respectively. The adhesion regulating molecule 1 (ADRM1) was detected in 98% of the cases. There was no correlation between the expression of any of the studied markers and clinical outcome or GC/non-GC phenotype.Conclusions: We suggest that UCHL5 and/or USP14 should be further evaluated as new targets for proteasome inhibitors in DLBCL. The lack of expression of PSMB5 on the tumour cells might provide an explanation of the relatively poor results of bortezomib in DLBCL.
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| 7. |
- Eloranta, Sandra, et al.
(author)
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Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000-2013
- 2018
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In: European Journal of Haematology. - : WILEY. - 0902-4441 .- 1600-0609. ; 100:1, s. 61-68
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Journal article (peer-reviewed)abstract
- Objectives: This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000-2013 in Sweden.Methods: Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100000 person-years and 95% confidence intervals (CI) were calculated, and PCNSL-specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison.Results: With 359 identified PCNSL cases (median age 66years), overall incidence was 0.26 (95% CI: 0.24-0.29) and the average annual increase 4% (P=.002). The increasing trend was primarily observed among elderly individuals (70+years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6years after diagnosis.Conclusion: The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population-based setting, although the presence of long-term survivors among fit patients is encouraging.
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| 8. |
- Englund, Annika, et al.
(author)
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The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children
- 2016
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 97:5, s. 430-438
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To study Hodgkin lymphoma (HL) microenvironment in a Swedish paediatric population and its relation to clinical parameters.METHODS: Tumour tissue from classical HL (cHL) (n=87) and nodular lymphocyte predominant HL (NLPHL) (n=11) was investigated for Epstein-Barr Virus (EBV) and analysed for eosinophils, mast cells and macrophages.RESULTS: In cHL, EBV positivity was more common in low age (p<0.001) and in mixed cellularity (MC) (p<0.001). Higher mast cell infiltration was seen in stage III-IV (p<0.001), and with presence of B-symptoms (p=0.01). Cases with high mast cell counts displayed higher erythrocyte sedimentation rate (ESR), lower haemoglobin and albumin levels. Higher macrophage infiltration was seen in stage III-IV (p=0.02) and there was elevated ESR and neutrophil count. All NLPHL cases were EBV negative, had lower rates of inflammatory cells and lower degree of inflammatory reaction in laboratory parameters. There was no difference in survival estimates with regard to infiltration of inflammatory cells.CONCLUSIONS: Higher levels of mast cells and macrophages in cHL tumours reflected the clinical presentation in laboratory parameters, B-symptoms and more advanced stages. NLPHL differs from cHL in numbers of inflammatory cells in the tumour, and in laboratory parameters. This article is protected by copyright. All rights reserved.
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| 9. |
- Hollander, Peter, et al.
(author)
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An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome
- 2018
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 100:1, s. 88-97
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Journal article (peer-reviewed)abstract
- Objective: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows anongoing inflammatory response consisting of varying degrees of infiltrating eosinophils,mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.Methods: Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.Results: The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05-3-15). Epstein-Barrvirus (EBV)-positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.Conclusions: Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.
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