| 1. |
- Cederleuf, Henrik, et al.
(författare)
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Outcome of peripheral T-cell lymphoma in first complete remission : a Danish-Swedish population-based study
- 2017
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 58:12, s. 2815-2823
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigate the outcome of 109 Danish and 123 Swedish patients with nodal PTCL in first complete remission (CR), and examine the impact of imaging-based follow-up (FU) strategies. The patients were selected by the following criteria: (a) newly diagnosed nodal PTCL from 2007 to 2012, (b) age ≥18 years, and (c) CR after CHOP or CHOEP therapy. FU guidelines in Sweden included symptom assessment, clinical examinations and blood tests at 3–4-month intervals for 2 years. FU strategies in Denmark was similar but included routine imaging, usually every 6 months for 2 years. Patients had fully comparable characteristics. Overall survival (OS) estimates for patients in CR were similar for all patients (p =.6) and in PTCL subtypes. In multivariate analysis, country of follow-up had no impact on OS. However, despite continuous CR for ≥2 years, the OS of PTCL remained inferior to a matched general population.
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| 2. |
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| 3. |
- Holst, Anders, et al.
(författare)
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Identifying causal relationships of cancer treatment and long-term health effects among 5-year survivors of childhood cancer in Southern Sweden
- 2022
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Ingår i: Communications medicine. - : Springer Science and Business Media LLC. - 2730-664X. ; 2, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Survivors of childhood cancer can develop adverse health events later in life. Infrequent occurrences and scarcity of structured information result in analytical and statistical challenges. Alternative statistical approaches are required to investigate the basis of late effects in smaller data sets.Methods: Here we describe sex-specific health care use, mortality and causal associations between primary diagnosis, treatment and outcomes in a small cohort ( n = 2315) of 5-year survivors of childhood cancer ( n = 2129) in southern Sweden and a control group ( n = 11,882; age-, sex- and region-matched from the general population). We developed a constraint-based method for causal inference based on Bayesian estimation of distributions, and used it to investigate health care use and causal associations between diagnoses, treatments and outcomes. Mortality was analyzed by the Kaplan-Meier method. Results: Our results confirm a significantly higher health care usage and premature mortality among childhood cancer survivors as compared to controls. The developed method for causal inference identifies 98 significant associations ( p < 0.0001) where most are well known ( n = 73; 74.5%). Hitherto undescribed associations are identified ( n = 5; 5.1%). These were between use of alkylating agents and eye conditions, topoisomerase inhibitors and viral infections; pituitary surgery and intestinal infections; and cervical cancer and endometritis. We discuss study-related biases ( n = 20; 20.4%) and limitations. Conclusions: The findings contribute to a broader understanding of the consequences of cancer treatment. The study shows relevance for small data sets and causal inference, and presents the method as a complement to traditional statistical approaches.
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| 4. |
- Petersson-Ahrholt, Magnus, et al.
(författare)
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Development and Implementation of Survivorship Tools to Enable Medical Follow-Up After Childhood Cancer Treatment in Southern Sweden
- 2019
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Ingår i: JCO clinical cancer informatics. - 2473-4276. ; 3, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Survival rates after childhood cancer have increased from 20% to 80% since the 1970s. The increased number of survivors emphasizes the importance of late effects and their monitoring. Late effects may have a strong impact on quality of life in survivors. The purpose of this study was to make key data in a quality registry available for direct clinical use, enabling health care professionals to perform efficient and appropriate long-term medical follow-up after childhood cancer treatment.METHODS: The population-based quality registry upon which this study is centered contains data on all individuals diagnosed with childhood cancer (diagnosed at 18 years of age or younger) in southern Sweden since January 1, 1970, and treatment data on 5-year survivors. Web tools, which were developed and implemented in a health care setting, generate a personalized treatment summary for each patient and enable risk group stratification of survivors.RESULTS: Generation of a personalized treatment summary and risk group stratification of survivors led to identification of women at risk for developing breast cancer as a consequence of childhood cancer treatment. Three novel cases of previously undiagnosed breast cancer were identified.CONCLUSION: The registry, together with the developed tools, enabled health care professionals to perform medical follow-up in this at-risk patient population.
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| 5. |
- Romerius, Patrik, et al.
(författare)
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Estrogen receptor alpha single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors
- 2011
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872. ; 21:5, s. 263-269
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. METHODS: Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127 adult childhood cancer survivors. RESULTS: In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients. CONCLUSION: Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered.
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| 6. |
- Romerius, Patrik, et al.
(författare)
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Estrogen receptor α single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors
- 2011
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 21:5, s. 263-269
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. METHODS: Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127 adult childhood cancer survivors. RESULTS: In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients. CONCLUSION: Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered.
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| 7. |
- Romerius, Patrik, et al.
(författare)
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High risk of azoospermia in men treated for childhood cancer.
- 2011
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Ingår i: International Journal of Andrology. - : Wiley. - 1365-2605 .- 0105-6263. ; 34, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- Summary Childhood cancer survivors (CCS) have an increased risk of impaired spermatogenesis, but data regarding the disease- and treatment-related risk factors of azoospermia are scarce. Such information is crucial both for counselling CCS and for selecting patients for testicular tissue cryopreservation. The proportion of azoospermic men in CCS was 18% [95% confidence interval (CI): 12-26], specifically for leukaemias (19%; 95% CI: 5.5-42), Hodgkin's disease (53%; 95% CI: 29-76), non-Hodgkin's lymphoma (11%; 95% CI: 0.28-48) and testicular cancer (11%; 95% CI: 0.28-48). In CCS treated with high doses of alkylating agents, the proportion of azoospermic men was 80% (95% CI: 28-99) and if radiotherapy was used additionally, the proportion was 64% (95% CI: 35-87). In CCS with subnormal Inhibin B levels, the proportion of azoospermic men was 66% (95% CI: 47-81) and for those with elevated follicle-stimulating hormone (FSH) levels, the proportion was 50% (95% CI: 35-67). Among CCS with subnormal testicular volume (
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| 8. |
- Romerius, Patrik, et al.
(författare)
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Hypogonadism Risk in Men Treated for Childhood Cancer.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 4180-4186
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Tidskriftsartikel (refereegranskat)abstract
- Context: Pediatric cancer treatment may imply an increased risk of hypogonadism, leading to metabolic disorders and osteoporosis. Such complications are potentially preventable. Objective: The aim of this study was to assess diagnosis- and treatment-dependent risk of hypogonadism in male childhood cancer survivors (CCS). Design: Male CCS who were treated during the period 1970-2002 and who in 2004 were 18-45 yr of age were eligible. Setting: The study was conducted in a university hospital clinic. Patients: A consecutive group of CCS treated at Lund University Hospital was selected for the study, of whom 151 (38%) agreed to participate. Furthermore, 141 healthy fertile men served as controls. Interventions: We measured serum levels of free and total testosterone, SHBG, and LH. Main Outcome Measures: Odds ratios (OR) for biochemical hypogonadism, defined as total testosterone less than 10 nmol/liter and/or LH above 10 IU/liter, were calculated and related to type of cancer, treatment received, as well as testicular volume. Results: Hypogonadism was more commonly detected in CCS than in controls (OR, 6.7; 95% CI, 2.7, 17). The increased presence of hypogonadism was noted in the following treatment groups: brain surgery, chemotherapy (with and without radiotherapy), and testicular irradiation. Low total testicular volume (
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| 9. |
- Romerius, Patrik, et al.
(författare)
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Sperm DNA Integrity in Men Treated for Childhood Cancer.
- 2010
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Ingår i: Clinical Cancer Research. - 1078-0432. ; Jul 1, s. 3843-3850
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: It is unknown whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study was to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), treatment regimen taken into account.EXPERIMENTAL DESIGN: In 99 CCS and 193 age-matched healthy controls, the DFI was assessed by the use of Sperm Chromatin Structure Assay.RESULTS: In the whole group of CCS DFI was increased as compared to the controls with borderline statistical significance (mean difference=0.94%; 95%CI: -0.0088; 3.7%). Those treated with radiotherapy only (mean difference=6.0%; 95%CI: 1.6; 10%) or surgery only (mean difference=2.9%; 95%CI: 0.083; 3.7%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS as compared to the control group (OR=2.2, 95%CI: 1.1; 4.4). For the radiotherapy only group the OR was even higher (OR=4.9, 95%CI 1.3; 18). The DFI was not associated to the dose of scattered testicular irradiation or the type of chemotherapy given.CONCLUSIONS: The DFI is increased in CCS, those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment and may have negative consequences in terms of fertility and risk of transmission to the offspring.
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| 10. |
- Ageberg, Malin, et al.
(författare)
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The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death.
- 2013
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Ingår i: American Journal of Translational Research. - 1943-8141. ; 5:2, s. 170-183
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematological malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60% of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC inhibitor valproic acid (VPA) on DLBCL cell lines. To elucidate the effects of VPA on chemo-sensitivity, we used a cell-line based model of CHOP-refractory DLBCL. All five DLBCL cell lines treated with VPA alone or in combination with CHOP showed decreased viability and proliferation. The VPA-induced sensitization of DLBCL cells to cytotoxic treatment resulted in increased number of apoptotic cell as judged by annexin V-positivity and the presence of cleaved caspase-3. In addition, pretreatment with VPA resulted in a significantly increased DNA-damage as compared to CHOP alone. In summary, HDAC inhibitors such as VPA, are promising therapeutic agents in combination with R-CHOP for patients with DLBCL.
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| 11. |
- Belfrage, Emma, et al.
(författare)
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Hudlymfom – ovanlig sjukdom ofta med lång tid till diagnos
- 2021
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Ingår i: Lakartidningen. - 0023-7205. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Primary cutaneous lymphoma is a heterogeneous group of diseases where the malignant lymphocytes are primarily present in the skin at the time of diagnosis. The most common type of primary cutaneous lymphoma is mycosis fungoides. Early stages of mycosis fungoides present with flat or slightly elevated red skin lesions and can resemble eczema or psoriasis. In advanced stages erythrodermia or skin tumors can develop. For many patients with mycosis fungoides effective albeit not curative treatment is available. Large randomized treatment studies for mycosis fungoides are largely lacking, which makes decisions on treatment strategy difficult. The new national clinical guidelines will hopefully enable more equal care for patients with mycosis fungoides and other types of primary cutaneous lymphoma in Sweden.
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| 12. |
- Cederleuf, Henrik, et al.
(författare)
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The addition of etoposide to CHOP is associated with improved outcome in ALK+ adult anaplastic large cell lymphoma : A Nordic Lymphoma Group study
- 2017
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 178:5, s. 739-746
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Tidskriftsartikel (refereegranskat)abstract
- Anaplastic large cell lymphomas (ALCLs) are rare CD30+ peripheral T-cell lymphomas (PTCLs) classified according to the expression of the anaplastic lymphoma kinase (ALK+) protein or not (ALK-). We have analysed the outcome and risk factors for survival in a population-based bi-national cohort of patients with systemic ALK+ ALCL. A total of 122 adult (≥18 years) patients diagnosed with ALK+ ALCL between 2000 and 2010 were identified from the Danish and Swedish lymphoma registries, representing 0·4% of all lymphomas. The median age of the cohort was 40 years (range 18-85). The 5-year overall survival and progression-free survival (PFS) was 78% and 64%, respectively. Age was strongly associated with outcome, and only bone marrow (BM) involvement was independently associated with poorer PFS in multivariate analysis (Hazard Ratio [HR] = 8·57, P < 0·001). Age stratification of the patients demonstrated an association between treatment with CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone) and improved overall survival for patients aged 41-65 years, even when adjusted for risk factors (HR = 0·38, P = 0·047). Our results suggest that the addition of etoposide to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) in the treatment for ALK+ ALCL seems reasonable in this age group.
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| 13. |
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| 14. |
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| 15. |
- d'Amore, Francesco, et al.
(författare)
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Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma
- 2010
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:5, s. 565-573
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty-one adult patients with relapsed or refractory CD4+ PTCL of non-cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL-not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single-arm multi-centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL-NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.
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| 16. |
- d'Amore, Francesco, et al.
(författare)
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Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma : NLG-T-01
- 2012
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:25, s. 3093-3099
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study. Patients and Methods Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT. Results Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL. Conclusion Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL. J Clin Oncol 30: 3093-3099. (C) 2012 by American Society of Clinical Oncology
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| 17. |
- Drott, Kristina, et al.
(författare)
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Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID)
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:12, s. 1386-1392
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the present study were to establish the maximally tolerated dose (MTD) of the histone deacetylase inhibitor valproate together with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with diffuse large B-cell lymphoma (DLBCL). A phase 1 dose escalation study of valproate together with R-CHOP followed by a dose expansion study using the established MTD of valproate was performed. MTD of valproate together with R-CHOP was established at 60 mg/kg per day, as higher doses resulted in auditory adverse events (AEs). In the study population, 2-year progression-free survival was 84.7% (95% confidence interval [CI], 73.2%-98%). The 2-year overall survival (OS) was 96.8% (n = 31; 95% CI, 90.8%-100%). These data were compared with 2 risk-factor matched populations of R-CHOP-treated patients from the Swedish Lymphoma Registry (cohort A, n = 330 and B, n = 165). As compared with the matched cohorts, we observed a statistically significant (P = .034 and 0.028, respectively) beneficial effect of the addition of valproate to R-CHOP on the OS in the studied population. In conclusion, addition of valproate to R-CHOP is a feasible strategy in first-line treatment of DLBCL. The proposed phase 2 dose is 60 mg/kg per day together with prednisone. Auditory AEs were unexpected and warrant close monitoring. Our findings suggest that drugs that target histone deacetylation may add benefit and are tolerable when combined with standard R-CHOP in DLBCL. The phase 1 trial was registered at www.clinicaltrials.gov as #NCT01622439.
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| 18. |
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| 19. |
- Eklund, Yvonne, et al.
(författare)
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Mycosis Fungoides: A Retrospective Study of 44 Swedish Cases.
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 96:5, s. 669-673
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Tidskriftsartikel (refereegranskat)abstract
- Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma with slow disease progression. There is a lack of descriptive data from Sweden concerning patients with this diagnosis. This study extracted data on patients admitted to the dermatology department at Lund University Hospital, Sweden from 1996 to 2010. Forty-four patients with clinically and histopathologically verified MF were identified during the period, with a mean follow-up time of 5.6 years. Median age at initial diagnosis was 64 years. In several cases other skin diseases preceded MF onset, such as non-specific dermatitis (32%) and parapsoriasis (30%). The majority of patients (86%, n = 38) had limited-stage (IA-IB) disease at the time of diagnosis. Overall response rate to psoralen plus ultraviolet A (PUVA) treatment was 81%. In adnexal MF, a trend to higher rate of progression to an advanced stage was observed when compared with non-adnexal disease (40% and 21%, respectively). Increased levels of soluble interleukin-2 (IL-2) receptor correlated with disease stage, being elevated in advanced stages or adnexal disease, but almost never in early non-adnexal limited-stage disease. Overall mortality was 25%, but only 11% could be verified as caused by MF.
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| 20. |
- Ellin, Fredrik, et al.
(författare)
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Central nervous system relapse in peripheral T-cell lymphomas: A Swedish lymphoma registry study.
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 126:1, s. 36-41
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Tidskriftsartikel (refereegranskat)abstract
- Central Nervous System (CNS) relapse in non-Hodgkin lymphomas (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, and the outcome of these patients, in a large population-based cohort of PTCL patients. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis disease characteristics at diagnosis independently associated with an increased risk of later CNS involvement were involvement of >1 extranodal site (Hazard Ratio [HR] 2.60, 95% Confidence Interval [95% CI] 1.07-6.29, p=0.035), skin (HR 3.51, 95% CI 1.26-9.74, p=0.016) and gastrointestinal involvement (HR 3.06, 95% CI 1.30-7.18, p=0.010). The outcome of relapsed/refractory patients was very poor and CNS involvement was not associated with a significantly worse outcome compared to relapsed/refractory patients without CNS involvement in multivariable analysis (HR 1.6, 95% CI 0.96-2.6, p=0.074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease.
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| 21. |
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| 22. |
- Ellin, Fredrik, et al.
(författare)
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Impact of comorbidity on survival in peripheral T-cell lymphomas : A Swedish Lymphoma Registry study
- 2018
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232. ; 36:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Comorbidity impacts survival in B-cell lymphoma patients, but the influence in peripheral T-cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P < .001) and progression-free survival (HR 1.54, P < .001) in multivariate analysis. In patients undergoing front-line autologous stem cell transplantation (auto SCT), CCI >0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low-intensity treatments. Among patients aged ≥75 years (n = 214), low-intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front-line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline-based chemotherapy in elderly PTCL patients might be of limited benefit.
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| 23. |
- Ellin, Fredrik, et al.
(författare)
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Real world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry.
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:10, s. 1570-1577
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral T-cell Lymphomas (PTCLs) are rare lymphomas with mostly poor outcome with current treatment. Addition of etoposide to CHOP and up-front consolidation with autologous stem cell transplantation (autoSCT) have shown promising results, but have never been tested in randomized trials. As a complement to retrospective analyses of clinical trials, we aimed at analyzing prognostic factors and outcome in an unselected, population-based cohort. Through the Swedish Lymphoma Registry we identified 755 PTCL patients diagnosed during a 10-year period. In addition to International Prognostic Index (IPI) factors, male gender was associated with an adverse overall survival (OS) (HR 1.28, p=0.011) and progression-free survival (PFS) (HR 1.26, p=0.014). In an intention-to-treat analysis in 252 nodal PTCL and EATL patients (excluding ALK-positive ALCL), up-front autoSCT was associated with a superior OS (HR 0.58, p=0.004) and PFS (HR 0.56, p=0.002) compared to patients treated without autoSCT. Addition of etoposide to CHOP resulted in superior PFS in patients up to 60 years (HR 0.49, p=0.008). This study is the largest population-based PTCL cohort reported so far and provides important information on outcome in PTCL outside the setting of clinical trials.
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| 24. |
- Ellin, Fredrik, et al.
(författare)
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Treatment outcome in T-cell lymphoblastic lymphoma in adults : a population-based study from the Swedish Lymphoma Registry
- 2014
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:7, s. 927-934
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Tidskriftsartikel (refereegranskat)abstract
- Background. T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor lymphoblast origin, for which there is no standard treatment for adults. Results of current treatment strategies in selected populations do exist but are largely unreported for unselected series. Here, we aimed to investigate treatment outcome in a population-based cohort. Material and methods. Patients were identified through the Swedish Lymphoma Registry and data was retrospectively collected for all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009. Results. A total of 39 patients with median age 40 years (range 18-78) were identified with females being significantly older than males (median age 66 vs. 37, p = 0.027). The five-year overall survival for all patients was 42%. Female gender was associated with shorter survival also when adjusted for treatment strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received intensive chemotherapy, otherwise used for treatment of acute lymphoblastic leukemia (ALL), which resulted in an overall response rate of 97% and a five-year progression-free survival (PFS) of 49%. In this group only CNS involvement at diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to progression compared to patients receiving only chemotherapy (p = 0.047). The major reason for treatment failure was relapse and in this series 18-fluoro-deoxyglucose positron emission tomography (PET) did not predict this risk. Conclusion. This population-based study indicates that all fit T-LBL patients should be considered for intensive treatment. Our results also suggest a beneficial effect of mediastinal irradiation in combination with hyper-CVAD treatment. Relapsing patients have a dismal outcome irrespective of salvage treatment.
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| 25. |
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| 26. |
- Kasteng, Frida, et al.
(författare)
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Cost-effectiveness of maintenance rituximab treatment after second line therapy in patients with follicular lymphoma in Sweden
- 2008
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:6, s. 1029-36
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Rituximab has significantly improved the prognosis for patients with both indolent and aggressive non-Hodgkin's lymphoma. An economic evaluation was carried out to assess the cost-effectiveness in Sweden of rituximab as maintenance therapy for patients with follicular lymphoma in remission after second line therapy. MATERIALS AND METHODS: The incremental cost and effectiveness of rituximab maintenance therapy versus observation were evaluated in a health-state transition model. Primary effect measures were quality-adjusted life-years (QALY) and life-years gained (LYG). Model state transitions were calculated based on progression-free and overall survival data from the EORTC20981 trial. The analysis was made from the perspective of the healthcare provider, including direct medical costs presented in euro, 2007 value. Effects and costs were discounted at a 3% annual rate. The stability of the base case results were tested in one-way and probabilistic sensitivity analyses. RESULTS: The evaluation assessed rituximab maintenance therapy to be associated with an incremental cost per QALY gained of euro 12,600 and an incremental cost per LYG of euro 11,200. The average discounted life expectancy for patients on rituximab maintenance was 1.0 year longer than for patients on observation (5.96 vs. 4.94 years). Rituximab maintenance was associated with an additional 0.9 QALY, and total costs per patient were euro 11,500 higher in the treatment arm, compared to observation. DISCUSSION: The results indicate that rituximab maintenance treatment after successful induction therapy for patients with relapsed/refractory follicular lymphoma in Sweden is cost-effective compared to observation.
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| 27. |
- Maurer, Matthew J., et al.
(författare)
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International Assessment of Event-Free Survival at 24 Months and Subsequent Survival in Peripheral T-Cell Lymphoma
- 2017
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 35:36, s. 4019-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort). EFS was defined as time from date of diagnosis to progression after primary treatment, retreatment, or death. Subsequent OS was measured after achieving EFS24 or from the time of progression if it occurred within 24 months. OS rates were compared with the age-, sex-, and country-matched general population. Results Seven hundred seventy-five patients were included in the study (the median age at diagnosis was 64 years; 63% were men). Results were similar in the initial and replication cohorts, and a combined analysis was undertaken. Sixty-four percent of patients progressed within the first 24 months and had a median OS of only 4.9 months (5-year OS, 11%). In contrast, median OS after achieving EFS24 was not reached (5-year OS, 78%), although relapses within 5 years of achieving EFS24 occurred in 23% of patients. Superior outcomes after achieving EFS24 were observed in younger patients (≤ 60 years of age: 5-year OS, 91%). Conclusion EFS24 stratifies subsequent outcome in PTCL. Patients with PTCL with primary refractory disease or early relapse have extremely poor survival. However, more than one third of patients with PTCL remain in remission 2 years after diagnosis with encouraging subsequent OS, especially in younger patients. These marked differences in outcome suggest that EFS24 has utility for patient counseling, study design, and risk stratification in PTCL.
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| 28. |
- Mead, Monica, et al.
(författare)
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Impact of comorbidity in older patients with peripheral T-cell lymphoma : an international retrospective analysis of 891 patients
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:7, s. 2120-2128
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive neoplasms with poor outcomes, commonly affecting older patients with comorbidities. This study aims to describe outcomes of older patients with PTCL in a large international cohort. Patients aged $70 years with PTCL diagnosed from 1 January 2010 to 31 December 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. Data on comorbidity were retrospectively collected according to the Charlson Comorbidity Index (CCI), and clinical outcomes were extracted. A total of 891 patients were included (SLR, n 5 173; CCR, n 5 718). Median age was 77 (SLR) and 78 (CCR) years. Included subtypes were as follows: angioimmunoblastic T-cell lymphoma, n 5 226; anaplastic large-cell lymphoma, n 5 122; enteropathy-associated T-cell lymphoma (EATL), n 5 31; hepatosplenic TCL, n 5 7; natural killer–/T-cell lymphoma, n 5 62; PTCL not otherwise specified, n 5 443. CCI data were available in 775 patients (87%), and CCI scores were divided into the groups CCI 5 0 (39%), CCI 5 1 (22%), and CCI . 1 (39%). Median age did not differ among the CCI groups (P 5 .72). Patients with a CCI . 1 had a worse median overall survival (4.4 months) compared with patients with CCI 5 0 (11.9 months) and CCI 5 1 (8.4 months; P, .001). Comorbidity and advancing age in as little as 5-year increments are important adverse factors in this group. Most patients died of lymphoma within a year from diagnosis, underscoring the importance of developing new treatments.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Relander, Thomas, et al.
(författare)
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Low level of gene transfer to and engraftment of murine bone marrow cells from long-term bone marrow cultures
- 2000
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Ingår i: Experimental Hematology. - 1873-2399. ; 28:4, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We wanted to determine whether the long-term bone marrow culture (LTBMC) transduction system would lead to efficient gene transfer and engraftment of murine repopulating hematopoietic stem cells (HSC), particularly in nonablated recipients. MATERIALS AND METHODS: Congenic mouse strains expressing Ly 5.1 or Ly 5.2 and the GP+E86 cell line producing the MGirL22Y vector carrying the gene for enhanced GFP were used. Murine LTBMCs were established and demi-depopulated on days 7 and 14 with addition of vector supernatant on days 8 and 15. RESULTS: Cell recovery on day 21 was 21.3%+/-3.8% of input cells and CFU-C recovery was 9.7+/-3.4% as compared with CFU-C of input cells. In vitro transduction efficiency determined by CFU-C expressing GFP was 22.2%+/-1.6%. In irradiated (950 cGy) mice transplanted with 2x10(6) LTBMC cells, 94% of nucleated cells in the blood at week 16 were of donor origin. However, GFP was only detected at low level in a few animals at week 4 and not later. Analysis of bone marrow from these mice at week 20 did not show any GFP expression and semiquantitative PCR revealed a transgene level of <1%. When 3.5-20.8x10(6) LTBMC cells (corresponding to 20-100x10(6) fresh cells) were transplanted to nonablated recipients, no engraftment or GFP expression were detected. Competitive repopulation experiments showed that the long-term repopulation ability (LTRA) of the LTMC cells was only 7% of fresh cells. CONCLUSION: These results indicate that LTBMC transduction of murine cells leads to low-level transduction of progenitors, no gene transfer to repopulating stem cells, and reduction in LTRA in ablated and nonablated recipients.
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| 34. |
- Relander, Thomas, et al.
(författare)
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Oncoretroviral gene transfer to NOD/SCID repopulating cells using three different viral envelopes
- 2002
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Ingår i: Journal of Gene Medicine. - : Wiley. - 1521-2254 .- 1099-498X. ; 4:2, s. 122-132
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study was to investigate gene transfer to human umbilical cord blood (CB) CD34(+)/CD38(low) and NOD/SCID repopulating cells using oncoretroviral vectors and to compare the transduction efficiency using three different viral envelopes. Methods CB cells were transduced on Retronectin using an MSCV-based vector with the gene for GFP (MGIN), which was packaged into three different cell lines giving different envelopes: PG13-MGIN (GALV) 293GPG-MGIN (VSV-G) or AM12-MGIN (amphotropic). Results Sorted CD34(+)/CD38(low) cells were efficiently transduced after 3 days of cytokine stimulation and the percentage of GFP-positive cells was 61.8+/-6.6% (PG13-MGIN), 26.9+/-3.5% (293GPG-MGIN), and 39.3+/-4.8% (AM12-MGIN). For transplantation experiments, CD34(+) cells were prestimulated for 2 days before transduction on Retronectin preloaded with vector and with the addition of 1/10th volume of viral supernatant on day 3. On day 4, the expanded equivalent of 2.5 x 10(5) cells was injected into irradiated NOD/SCID mice. All three pseudotypes transduced NOD/SCID repopulating cells (SRCs) equally well in the presence of serum, but engraftment was reduced when compared with freshly thawed cells. Simultaneous transduction with all three vector pseudotypes increased the gene transfer efficiency to SRCs but engraftment was significantly impaired. There were difficulties in producing amphotropic vectors at high titers in serum-free medium and transduction of CD34(+) cells using VSV-G-pseudotyped vectors under serum-free conditions was very inefficient. In contrast, transduction with PG13-MGIN under serum-free conditions resulted in the maintenance of SRCs during transduction, high levels of engraftment (29.3+/-6.6%), and efficient gene transfer to SRCs (46.2+/-4.8%). Conclusions The best conditions for transduction and engraftment of CB SRCs were obtained with GALV-pseudo typed vectors using serum-free conditions. Copyright (C) 2002 John Wiley Sons, Ltd.
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| 35. |
- Relander, Thomas, et al.
(författare)
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Overexpression of Gibbon Ape Leukemia Virus (GALV) Receptor (GLVR1) on Human CD34(+) Cells Increases Gene Transfer Mediated by GALV Pseudotyped Vectors.
- 2002
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; 6:3, s. 400-406
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Tidskriftsartikel (refereegranskat)abstract
- Retroviral transduction of CD34(+) cells on Retronectin using gibbon ape leukemia virus (GALV) pseudotyped vectors is inhibited by high concentrations of vector containing medium (VCM). Furthermore, this inhibitory activity is stable for at least 48 hours at 37 degrees C and partially blocks a second hit with a GALV pseudotyped vector. We hypothesized that this inhibition was due to interference at the receptor level between infectious and noninfectious vector particles and that it might be possible to overcome it by increasing receptor expression on target cells. Activation of protein kinase C in CD34(+) cells with the phorbol ester PMA (phorbol 12-myristate 13-acetate) increased the mRNA level of the GALV receptor (GLVR1) and the transduction efficiency (TE), and fully reversed the inhibition of transduction seen with high-titer GALV VCM. A murine stem cell virus (MSCV) vector with the GLVR1 receptor and green fluorescent protein cDNAs (MGLIG) was used to transduce fibroblasts, and clones expressing different levels of GLVR1 were isolated. The TE of these cells using a GALV vector correlated with the level of GLVR1 expression. When CD34(+) cells or K562 cells were first transduced with MGLIG and then with high-titer GALV VCM, no inhibition of transduction was seen. The low level of GLVR1 expression limits gene transfer to K562 and CD34(+) cells using GALV pseudotyped vectors, especially in the presence of high-titer VCMs.
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| 36. |
- Relander, Thomas
(författare)
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Retroviral gene transfer to repopulating hematopoietic cells
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hematopoietic stem cells (HSCs) have the capacity to maintain hematopoiesis throughout life. HSCs are ideal targets for permanent gene transfer, as the transgene will be expressed in all the progeny of the gene-modified stem cells. The aim of this thesis was to optimize conditions for retroviral gene transfer to human candidate HSCs and to study mechanisms interfering with efficient gene transfer. First, long-term bone marrow culture transduction of murine hematopoietic cells was investigated, showing inefficient gene transfer and loss of repopulating ability of the transduced cells. Thereafter, transduction of human CD34+ cells was studied using the MGIN vector with the GALV, amphotropic and VSV-G envelopes. Amphotropic, and, particularly, GALV vector containing medium (VCM) inhibited transduction on fibronectin preloaded with vector. GALV VCM inhibited transduction of NOD/SCID repopulating cells (SRCs) as well. Optimal transduction was seen with vector preloaded to fibronectin and cells added in medium without vector. To study the mechanisms underlying GALV vector mediated inhibition, the GLVR1 receptor was overexpressed using phorbol ester or a retroviral vector, showing complete abolishment the inhibitory effect from GALV VCM. Together our results show that low levels of GLVR1, in combination with non-infectious vector particles in VCM, limit transduction of hematopoietic progenitors. Finally, vectors with GALV, amphotropic and VSV-G envelopes were compared regarding their ability to transfer genes to SRCs. The different pseudotypes were equally efficient in the presence of serum with an average transduction efficiency of 25-33 % of SRCs, but the engraftment levels were reduced compared to fresh cells. Only the GALV vectors could be used under serum-free conditions showing high level transduction of SRCs (46 %) without loss of SRC frequency as analyzed by transplantation at limiting cell numbers. In conclusion, under optimal conditions, highly efficient gene transfer human hematopoietic cells with NOD/SCID repopulating ability could be accomplished. However, for clinical applications, safety issues, particularly regarding the risk of mutagenesis from retroviral vector insertion into the genome of repopulating cells, need to be adressed carefully.
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| 37. |
- Relander, Thomas, et al.
(författare)
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Retroviral transduction of human CD34+ cells on fibronectin fragment CH-296 is inhibited by high concentrations of vector containing medium
- 2001
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Ingår i: Journal of Gene Medicine. - 1521-2254. ; 3:3, s. 207-218
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of the present study was to optimize conditions for retroviral transduction of human cord blood (CB) CD34+ cells and to reveal mechanisms which interfere with efficient gene transfer. METHODS: An MSCV based retroviral vector with the gene for enhanced green fluorescent protein (MGIN) produced by GP+envAM12 (amphotropic envelope), PG13 (gibbon ape leukemia virus envelope) or 293GPG (vesicular stomatitis virus envelope) cell lines was used to transduce cord blood CD34+ cells on Retronectin (fibronectin fragment CH-296) in three different ways: either in vector containing medium (VCM), in fresh medium on Retronectin pre-loaded with vector or in VCM on Retronectin pre-loaded with vector. RESULTS: Paradoxically, the transduction efficiency obtained with pre-load of vector onto Retronectin alone was higher than pre-load plus VCM for PG13-MGIN (67.9 +/- 6.0% vs 24.9 +/- 8.0%) and AM12-MGIN (47.5 +/- 5.8% vs 38.7 +/- 2.2%). Further experiments showed that transduction on Retronectin pre-loaded with PG13-MGIN or AM12-MGIN was inhibited by the presence of the same VCM at high concentrations, but not by the presence of a VCM with a different receptor specificity. If no pre-load of vector was performed, the highest transduction efficiencies were seen when VCMs were diluted 1:10 (MOIs of 3). The inhibitory effect of high titer PG13-MGIN VCM was confirmed in more primitive CD34+CD38low cells and in NOD/SCID repopulating cells, and was also seen in experiments with bone marrow CD34+ cells. CONCLUSIONS: Retroviral transduction of CB CD34+ cells on Retronectin is inhibited by high titer PG13 and GP+envAM12 vector containing medium. Efficient gene transfer to human hematopoietic cells can be obtained by preload alone of the vector onto Retronectin. These findings are of importance for the design of transduction protocols for repopulating hematopoietic cells.
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| 38. |
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| 39. |
- Strang, BL, et al.
(författare)
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Human immunodeficiency virus type 1 vectors with alphavirus envelope glycoproteins produced from stable packaging cells
- 2005
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Ingår i: Journal of Virology. - 1098-5514. ; 79:3, s. 1765-1771
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Tidskriftsartikel (refereegranskat)abstract
- Alphavirus glycoproteins have broad host ranges. Human immunodeficiency virus type 1 (HIV-1) vectors pseudotyped with their glycoproteins could extend the range of tissues that can be transduced in both humans and animal models. Here, we established stable producer cell lines for HIV vectors pseudotyped with alphavirus Ross River virus (RRV) and Semliki Forest virus (SFV) glycoproteins E2E1. RRV E2E1-stable clones could routinely produce high-titer pseudotyped vectors for at least 5 months. SFV E2E1-stable clones, however, produced relatively low titers. We examined the properties of RRV E2E1-pseudotyped vectors [HIV-1(RRV)] and compared them with amphotropic murine leukemia virus Env- and vesicular stomatitis virus glycoprotein G-pseudotyped vectors. HrV-1 (RRV) displayed a number of characteristics which would be advantageous in ex vivo and in vivo experiments, including resistance to inactivation by heat-labile components in fresh human sera and thermostability at 37degreesC. Upon single-step concentration by ultracentrifugation of HIV-1(RRV), we could achieve vector stocks with titers up to 6 x 10(7) IU/ml. HIV-1(RRV) efficiently transduced cells from several different species, including murine primary dendritic cells, but failed to transduce human and murine T cells as well as human hematopoietic stem cells (HSC). These results indicate that HIV-1(RRV) could be used in a number of applications including animal model experiments and suggest that expression of RRV cellular receptors is limited or absent in certain cell types such as T cells and human HSC.
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| 40. |
- Villumsen, Marie, et al.
(författare)
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Risk of lymphoma and leukaemia after bacille Calmette-Guerin and smallpox vaccination: A Danish case-cohort study
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 27:49, s. 6950-6958
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Tidskriftsartikel (refereegranskat)abstract
- Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines. In a background cohort (N=47,622) from the Copenhagen School Health Records Register, cases of leukaemia (N=20) and lymphoma (N=51) were identified through the Danish Cancer Registry. The vaccination status of the cases was compared with the vaccination status of a 5% random sample (N = 2073) of the background cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81(0.31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas. (C) 2009 Elsevier Ltd. All rights reserved.
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