Chronic cold agglutinin disease (CAD) is an acquired autoimmune hemolytic anemia. Previous therapeutic modalities, including alkylating cytostatics, interferon and prednisolone, have been disappointing. However, several case reports and small-scaled studies have demonstrated promising results after treatment with rituximab. We performed a phase II multicentre trial to investigate the effect of rituximab in CAD, including 20 patients studied from October 2002 until April 2003. Thirteen patients had idiopathic CAD and seven patients had CAD associated with a malignant B-cell lymphoproliferative disease. Rituximab was given in doses of 375 mg/m(2) at days 1, 8, 15 and 22. Sixteen patients were followed up for at least 48 weeks. Four patients were excluded after 8, 16, 23 and 28 weeks for reasons unrelated to CAD. Nine patients (45%) responded to the treatment, one with complete response (CR), and eight with partial response. Eight patients relapsed, one patient was still in remission at the end of follow-up. There were no serious rituximab-related side-effects. Our study confirms previous findings of a favourable effect of rituximab in patients with CAD. However, few patients will obtain CR and, in most patients, the effect will be transient.

SummaryThe impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and rituximab combined (N = 32) or prednisolone monotherapy (N = 32). After 12 months, a satisfactory response was observed in 75% of the patients treated with rituximab and prednisolone but in a significantly smaller proportion (36%) of those given prednisolone alone (P = 0Á003). Furthermore, relapse-free survival was significantly better after the combined therapy than after prednisolone monotherapy (P = 0Á02). After 36 months, about 70% of the patients were still in remission in the rituximab-prednisolone group, whereas only about 45% were still in complete or partial remission in the prednisolone group. There was no significant difference between the two groups regarding adverse reactions to the studied medications. Likewise, serious adverse events were equally distributed, and no allergic reactions to rituximab were recorded. In conclusion, our data show that using rituximab and prednisolone combined rather than prednisolone alone as first-line treatment in WAIHA increases both the rate and the duration of the response.

Allergy may not be causally associated with the risk of non-Hodgkin lymphoma. The inverse association observed in some case-control studies may arise because non-Hodgkin lymphoma suppresses the immunologic response to allergens.

Smoking is not considered a risk factor for chronic lymphocytic leukemia (CLL) yet increased lung cancer risk has been reported for these patients. Little data exist on the temporal variation in lung cancer risk after CLL, or its histological composition. We investigated the occurrence of second cancers in a large cohort of CLL patients with particular emphasis on lung cancer and its major subtypes. We followed all patients diagnosed with CLL in Denmark in the period 1943-2003 (n 5 12,373) for the occurrence of second cancers. The relative risk was expressed as the standardized incidence ratio (SIR), i.e. the ratio of observed to expected number of cancers, based on incidence rates for the Danish population. During follow-up 1,105 cancers occurred among the CLL patients (SIR 5 1.59 (95% CI 1.50-1.69)). SIR for all cancers combined remained elevated more than 10 years after CLL (SIR 5 1.80 (1.56-2.08)). Lung cancer occurred in 141 patients (SIR 5 1.61 (1.37-1.90)). The relative risk of lung cancer did not vary by gender, or time of follow-up, but was higher in younger (SIR <60 years 5 2.22 (1.62-3.06)) than in older (SIR 70-79 years 5 1.21 (0.88-1.68)) age-groups. Elevated risks were observed for adenocarcinoma (SIR 5 2.20 (1.57-3.08)) and squamous cell carcinoma (SIR 5 1.52 (1.06-2.17)) of the lung. We speculate that shared genetic risk factors may explain the accumulation of lung and other cancers in CLL patients. ' 2007 Wiley-Liss, Inc.Key words: CLL; second cancer; cohort study; epidemiology In Western countries chronic lymphocytic leukemia (CLL) accounts for 25-30% of all leukemias.1 Clinically the disease varies substantially: while in many patients it remains indolent with no need for treatment, in others it displays an aggressive clinical course. Consequently the 7-years median survival time for CLL ranges from a few months to several decades. 2The causes of CLL largely have remained unestablished, 3-5 but there is increasing evidence that its development involves both constitutional and environmental factors. 6,7 Little is known about the nature of these factors, but important clues could emanate from studies of comorbidity in CLL patients, e.g. the occurrence of second cancers.Previous studies have indicated that patients with CLL have an increased risk of subsequent cancer, in particular cancers of the skin and lung. [8][9][10][11][12] Several mechanisms have been discussed for the association between these cancers. The increased risk of lung cancer is particularly noteworthy, because smoking has so far not been linked with CLL risk. 13,14 In previous Danish 11 and American 10 studies, the increased risk of lung cancer was found to be independent of time since CLL diagnosis, leading to the conclusion that it could not be attributed to CLL treatment offered no explanation for the observed increased lung cancer risk. However, concomitant with the introduction of new treatment strategies including the nucleoside analog Fludarabine, other studies have reported both increased risk of lung cancer, 15-17 an...

The association between hepatitis C virus (HCV) infection and risk of malignant lymphoma remains controversial, perhaps due to small-sized studies and low prevalence of HCV in the general population. On the basis of a large Danish-Swedish populationbased case-control study, 2,819 lymphoma patients and 1,856 controls of second-generation Danish-Swedish origin were screened for HCV infection using an enzyme-linked immunosorbent assay and a confirming recombinant immunoblot assay (RIBA) test. Positive samples were tested with real-time PCR for the presence of HCV RNA. The association between HCV infection and risk of malignant lymphoma was assessed by logistic regression. When intermediate RIBA test results were interpreted as positive, anti-HCV antibody positivity was associated with a nonsignificant increased risk of non-Hodgkin lymphoma (NHL) overall (odds ratio (

Reports of the presence of

No abstract

BackgroundThe calreticulin (CALR) exon 9 mutations that are identified in 20% of patients with Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPN) generate immunogenic antigens. Thus, therapeutic cancer vaccination against mutant CALR could be a new treatment modality in CALR-mutant MPN.MethodsThe safety and efficacy of vaccination with the peptide CALRLong36 derived from the CALR exon 9 mutations was tested in a phase I clinical vaccination trial with montanide as adjuvant. Ten patients with CALRmut MPN were included in the trial and received 15 vaccines over the course of one year. The primary end point was evaluation of safety and toxicity of the vaccine. Secondary endpoint was assessment of the immune response to the vaccination epitope (www.clinicaltrials.gov identifier NCT03566446).ResultsPatients had a median age of 59.5 years and a median disease duration of 6.5 years. All patients received the intended 15 vaccines, and the vaccines were deemed safe and tolerable as only two grade three AE were detected, and none of these were considered to be related to the vaccine. A decline in platelet counts relative to the platelets counts at baseline was detected during the first 100 days, however this did not translate into neither a clinical nor a molecular response in any of the patients. Immunomonitoring revealed that four of 10 patients had an in vitro interferon (IFN)-γ ELISPOT response to the CALRLong36 peptide at baseline, and four additional patients displayed a response in ELISPOT upon receiving three or more vaccines. The amplitude of the immune response increased during the entire vaccination schedule for patients with essential thrombocythemia. In contrast, the immune response in patients with primary myelofibrosis did not increase after three vaccines.ConclusionTherapeutic cancer vaccination with peptide vaccines derived from mutant CALR with montanide as an adjuvant, is safe and tolerable. The vaccines did not induce any clinical responses. However, the majority of patients displayed a marked T-cell response to the vaccine upon completion of the trial. This suggests that vaccines directed against mutant CALR may be used with other cancer therapeutic modalities to enhance the anti-tumor immune response.