Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) ؉ cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R ؉ highdose cytarabine. Responders received highdose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progressionfree survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.

Our results confirm the associations between certain autoimmune disorders and risk of NHL and suggest that the associations may not be general but rather mediated through specific NHL subtypes. These NHL subtypes develop during postantigen exposure stages of lymphocyte differentiation, consistent with a role of antigenic drive in autoimmunity-related lymphomagenesis.

This retrospective study confirms that most so-called MFH can be subclassified by defined criteria; it provides evidence that such classification is clinically important. Specifically, pleomorphic STS showing myogenic differentiation are significantly more aggressive, a finding that allows planning future therapeutic trials.

Background: Numerous studies have reported on the association between coeliac disease and the otherwise uncommon enteropathy-type T cell lymphoma (ETTL). A systematic risk assessment of more prevalent lymphoma entities, such as B cell and non-intestinal lymphomas, in coeliac disease has not been performed. Aims: In light of the increasing number of patients diagnosed with coeliac disease and the unknown aetiology of malignant lymphomas, we aimed to estimate the distribution and risk of lymphoma subtypes in coeliac disease. Methods: We reviewed and reclassified 56 cases of incident malignant lymphomas occurring in a Swedish population based cohort of 11 650 patients hospitalised with coeliac disease. The observed numbers of lymphoma subtypes were compared with those expected in the Swedish population. Results: The majority (n = 32, 57%) of lymphomas in the cohort were not intestinal T cell lymphomas. Significantly increased risks were observed for B cell non-Hodgkin lymphoma (NHL) (standardised incidence ratio (SIR) 2.2 (95% confidence interval (CI) 1.2-3.6); 11 non-intestinal and five intestinal) and for lymphomas of non-intestinal origin (SIR 3.6 (95% CI 2.3-5.2), 11 B and 14 T cell). Furthermore, 44% of patients with B cell NHL had a history of other autoimmune/inflammatory diseases. The relative risks for T cell NHL (SIR 51 (95% CI 35-68); n = 37) and for primary gastrointestinal lymphomas ; five B and 25 T cell) were markedly increased, as anticipated. Conclusion: Most lymphomas complicating coeliac disease are indeed related to the disease and are not of the ETTL-type. There was a remarkable aggregation of autoimmune/inflammatory disorders, female sex, coeliac disease, and B cell lymphoma.

Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (<11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an osteosarcoma cell line exposed to irradiation. A linear correlation was found between the frequency of abnormalities in nuclear shape, on one hand, and cells with unstable chromosomes (r = 0.87) and anaphase bridge configurations (r = 0.98), on the other hand. The relation between nuclear shape and karyotypic pattern was investigated further in cultures from 58 tumors of bone, soft tissue, and epithelium. Blebs, strings, and micronuclei were significantly more frequent in tumors that contained rings, dicentrics, or telomeric associations than in those exhibiting only stable aberrations (P: < 0.001) and a positive correlation (r = 0.78) was found between the frequency of such nuclear abnormalities and the intratumor heterogeneity of structural chromosome aberrations. These results indicate that the formation of nuclear blebs, chromatin strings, and micronuclei in malignant tissues is closely related to the breakage-fusion-bridge type of mitotic disturbances. Abnormalities in nuclear shape may thus primarily be regarded as an indicator of genetic instability and intratumor heterogeneity, independent of cytogenetic complexity and the grade of malignancy.

Patients with anaplastic thyroid carcinoma can rarely be cured, but every effort should be made to prevent death due to suffocation. Between 1984 and 1999, 55 consecutive patients with anaplastic thyroid carcinoma were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin, and when feasible surgery. Radiotherapy was carried out for 5 days a week. The daily fraction until 1988 was 1.0 Gy×2 (A) and 1989–92 1.3 Gy×2 (B) . Thereafter 1.6 Gy×2 (C) was administered. Radiotherapy was administered to a total target dose of 46 Gy; of which 30 Gy was administered preoperatively in the first two protocols (A and B), while the whole dose was given preoperatively in the third protocol (C). The therapy was otherwise identical. Twenty mg doxorubicin was administered intravenously weekly. Surgery was possible in 40 patients. No patient failed to complete the protocol due to toxicity. In only 13 cases (24%) was death attributed to local failure. Five patients (9%) ‘had a survival’ exceeding 2 years. No signs of local recurrence were seen in 33 patients (60%); 5 out of 16 patients in Protocol A, 11 out of 17 patients in Protocol B, 17 out of 22 patients in Protocol C ( P =0.017). In the 40 patients undergoing additional surgery, no signs of local recurrence were seen in 5 out of 9 patients, 11 out of 14 patients and 17 out of 17 patients, respectively ( P =0.005). British Journal of Cancer (2002) 86 , 1848–1853. doi: 10.1038/sj.bjc.6600361 www.bjcancer.com © 2002 Cancer Research UK

Background: Soft tissue sarcoma (STS) diagnosis is challenging because of a multitude of histopathological subtypes, different genetic characteristics, and frequent intratumoral pleomorphism. One-third of STS metastasize and current risk-stratification is suboptimal, therefore, novel diagnostic and prognostic markers would be clinically valuable. We assessed the diagnostic and prognostic value of array-based gene expression profiles using 27 k cDNA microarrays in 177, mainly high-grade, STS of 13 histopathological subtypes.

We report a population based case-control study of exposure to pesticides as risk factor for non-Hodgkin lymphoma (NHL). Male and female subjects aged 18-74 years living in Sweden were included during December 1, 1999, to April 30, 2002. Controls were selected from the national population registry. Exposure to different agents was assessed by questionnaire. In total 910 (91%) cases and 1016 (92%) controls participated. Exposure to herbicides gave odds ratio (OR) 1.72, 95% confidence interval (CI) 1.18-2.51. Regarding phenoxyacetic acids highest risk was calculated for MCPA; OR 2.81, 95% CI 1.27-6.22, all these cases had a latency period >10 years. Exposure to glyphosate gave OR 2.02, 95% CI 1.10-3.71 and with >10 years latency period OR 2.26, 95% CI 1.16-4.40. Insecticides overall gave OR 1.28, 95% CI 0.96-1.72 and impregnating agents OR 1.57, 95% CI 1.07-2.30. Results are also presented for different entities of NHL. In conclusion our study confirmed an association between exposure to phenoxyacetic acids and NHL and the association with glyphosate was considerably strengthened.