Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia.

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding symptoms. A total of 133 patients were randomly assigned to either dexamethasone 40 mg/day for 4 days (n = 71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n = 62). Patients were allowed supplemental dexamethasone every 1 to 4 weeks for up to 6 cycles. Our primary end point, sustained response (ie, platelets ≥50×10(9)/L) at 6 months follow-up, was reached in 58% of patients in the rituximab + dexamethasone group vs 37% in the dexamethasone group (P = .02). The median follow-up time was 922 days. We found longer time to relapse (P = .03) and longer time to rescue treatment (P = .007) in the rituximab + dexamethasone group. There was an increased incidence of grade 3 to 4 adverse events in the rituximab + dexamethasone group (P = .04). In conclusion, rituximab + dexamethasone induced higher response rates and longer time to relapse than dexamethasone alone. This study is registered at http://clinicaltrials.gov as NCT00909077.

Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients.

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.

Phase II study of palliative low-dose local radiotherapy in disseminated indolent non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

PURPOSE: Indolent non-Hodgkin's lymphoma (INHL) and chronic lymphocytic leukemia (CLL) are highly sensitive to radiotherapy (RT). Previous retrospective studies have shown high response rates after local palliative RT of 4 Gy in 2 fractions, which prompted this prospective Phase II trial of the palliative effect of this regimen in patients with disseminated INHL or CLL. METHODS AND MATERIALS: Twenty-two patients (11 men, 11 women, median age 62 years, range 30-89) with disseminated INHL (n = 15) or CLL (n = 7) were treated with local low-dose RT, 2 Gy x 2 within 3 days, with the aim of achieving palliation from localized lymphoma masses. The patients were treated to a total of 31 different sites. Seventeen patients had previously been treated with chemotherapy. The median observation time after the start of RT was 8 months (range 3-26). RESULTS: All patients and all irradiated sites were assessable for response. Of the 22 patients, 18 responded to the treatment, corresponding to an overall response rate (RR) of 82%; 12 patients (55%) achieved a complete response (CR), 5 patients (22%) a partial response (PR), and 1 patient had a CR at three sites and a PR at one site. Of the 31 irradiated sites, 27 responded to treatment, corresponding to an overall RR of 87%; in 20 sites (65%) a CR was achieved and in 7 sites (22%) a PR. Patients with disseminated INHL had an overall RR of 87% (74% CR, 13% PR); patients with CLL had an overall RR of 71% (29% CR, 42% PR). The median duration of response was estimated at 22 months. None of the patients had significant side effects from the treatment. CONCLUSION: Low-dose RT (4 Gy in 2 fractions) is a highly effective palliative treatment of localized lymphoma masses in patients with disseminated INHL and CLL. The treatment has minimal side effects.

Ultraviolet radiation exposure and risk of malignant lymphomas.

BACKGROUND: The incidence of malignant lymphomas has been increasing rapidly, but the causes of these malignancies remain poorly understood. One hypothesis holds that exposure to ultraviolet (UV) radiation increases lymphoma risk. We tested this hypothesis in a population-based case-control study in Denmark and Sweden. METHODS: A total of 3740 patients diagnosed between October 1, 1999, and August 30, 2002, with incident malignant lymphomas, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Hodgkin lymphoma, and 3187 population controls provided detailed information on history of UV exposure and skin cancer and information on other possible risk factors for lymphomas. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. Statistical tests were two-sided. RESULTS: Multivariable-adjusted analyses revealed consistent, statistically significant negative associations between various measures of UV light exposure and risk of non-Hodgkin lymphoma. A high frequency of sun bathing and sunburns at age 20 years and 5-10 years before the interview and sun vacations abroad were associated with 30%-40% reduced risks of non-Hodgkin lymphoma (e.g., for sunbathing four times a week or more at age 20 versus never sunbathing, OR = 0.7, 95% CI = 0.6 to 0.9; for two or more sunburns a year at age 20 versus no sunburns, OR = 0.6, 95% CI = 0.5 to 0.8). These inverse associations increased in strength with increasing levels of exposure (all P(trend)< or =.01). Similar, albeit weaker, associations were observed for Hodgkin lymphoma. There were no clear differences among non-Hodgkin lymphoma subtypes, although associations were stronger for B-cell than for T-cell lymphomas. A history of skin cancer was associated with a doubling in risks of both non-Hodgkin and Hodgkin lymphoma. CONCLUSIONS: A history of high UV exposure was associated with reduced risk of non-Hodgkin lymphoma. The positive association between skin cancer and malignant lymphomas is, therefore, unlikely to be mediated by UV exposure.

Successful treatment of anemia in idiopathic myelofibrosis with recombinant human erythropoietin.

Thirteen patients with idiopathic myelofibrosis (5 osteomyelosclerosis) were treated with recombinant human erythropoietin (rHuEpo) for transfusion-dependent anemia. All but 7 patients were concomitantly treated with alpha interferon, and 5 patients also received a interferon before the start of erythropoietin (EPO) treatment. All but two patients became transfusion independent. The highly positive results of the present study of transfusion-dependent patients with idiopathic myelofibrosis calls for further studies to delineate more precisely in larger series those patients who are likely to respond to rHuEpo.

Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis.

Imatinib mesylate targets the adenosine triphosphate (ATP)-binding sites of the protein tyrosine kinase domains associated with Bcr-abl, the platelet-derived growth factor (PDGF) and c-kit. In idiopathic myelofibrosis (IMF) PDGF is considered to be one of the growth factors responsible for the development of bone marrow fibrosis. Recently, it has been shown that imatinib has antifibrogenic effect on bone marrow fibrosis in chronic myelogenous leukemia. Treatment with imatinib alone in IMF has been associated with significant side effects. In this study, the safety and efficacy of imatinib therapy in IMF, either administered as a single agent or in combination with hydroxyurea (HU) and/or alpha-interferon (IFN-alpha) are evaluated. Eleven patients (median age, 63 years; range, 33-82 years) with IMF (n = 8) or postpolycythemic myelofibrosis (PPMF) (n = 3) were studied All patients had been treated with HU (n = 9) and/or IFN (n = 7) before study entry. In all but one patient, treatment with these agents was discontinued when imatinib therapy was instituted. One patient continued IFN when treatment with imatinib was started. Imatinib was given at a dose of 400 mg/day. Nine patients were in an advanced disease phase. The patients have been followed for a median period of 2 months (range, 0.5-12 months). Treatment with imatinib has been stopped in six patients (55%), because of overt side effects (n = 4), recurrence of transitory dizziness and visual defects owing to a rising platelet count (n = 1), or the occurrence of an acute subdural hemorrhage that was evacuated without neurological deficits (n = 1). In nine patients imatinib treatment was followed by a rise in leukocyte and platelet counts that required combination with HU or IFN. The combined treatment modalities were followed by a rapid decrease in cell counts and were well tolerated apart from IFN side effects. A beneficial effect of imatinib was documented in three patients. It is concluded that leukocytosis and thrombocytosis are seen in most patients with myelofibrosis during treatment with imatinib. Combination therapy with HU or IFN seems safe and well tolerated and followed by a decrease in disease activity. A subgroup of patients in an early disease phase might benefit from imatinib therapy alone.