Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Immune thrombocytopenia is characterised by immune-mediated destruction and suboptimum production of platelets. Despite the absence of supporting evidence, rituximab is frequently used off-label in patients with immune thrombocytopenia. We aimed to assess the efficacy of rituximab as compared with placebo as a splenectomy-sparing treatment in patients who were previously treated with corticosteroids. METHODS: In this multicentre, randomised, double-masked, placebo-controlled trial, we enrolled corticosteroid unresponsive adult patients (aged ≥18 years) with primary immune thrombocytopenia and a platelet count of less than 30 × 10(9) platelets per L. Patients were randomly assigned (1:1) to four weekly infusions of 375 mg/m(2) rituximab or placebo. Concurrent treatment with corticosteroids only was allowed during the study. The primary endpoint was rate of treatment failure within 78 weeks--a composite of splenectomy or meeting criteria for splenectomy after week 12 if splenectomy was not done, assessed in all patients who received at least one dose of study treatment. Secondary endpoints were response rates, relapse rates, and duration of response. Efficacy endpoints were assessed with the Kaplan-Meier method. Safety endpoints were assessed in all patients who received at least one dose. This trial is registered with ClinicalTrials.gov, number NCT00344149. FINDINGS: Between Aug 17, 2006, and June 30, 2011, we enrolled 112 patients. 32 (58%) of 55 patients in the rituximab group and 37 (69%) of 54 patients in the placebo group had treatment failure within 78 weeks (Kaplan-Meier cumulative incidence 46% for rituximab vs 52% for placebo (hazard ratio [HR] 0·89, 95% CI 0·55-1·45; p=0·65). The cumulative incidence of overall response was 81% in the rituximab group versus 73% in the placebo group (p=0·15) and complete response was 58% in the rituximab group versus 50% in the placebo group (p=0·12). Of those achieving an overall response, 68% relapsed in the rituximab group and 78% relapsed in the placebo group, and of those achieving complete response, 50% relapsed in the rituximab group and 62% relapsed in the placebo group. Time to relapse in the rituximab group was longer in patients who achieved overall response (36 vs 7 weeks; p=0·01) but not complete response (76 vs 49 weeks; p=0·19). Rates of bleeding were similar in the two groups (21 [38%] in the rituximab group vs 27 [50%] in the placebo group; p=0·08) as were rates of infection (22 [40%] vs 13 [24%]; p=0·09). INTERPRETATION: Despite no reduction in the rate of long-term treatment failure with rituximab, a small benefit cannot be ruled out, as suggested by an apparently longer duration of response and numerically higher response rates with rituximab. FUNDING: South-East Regional Health Authority and Østfold Hospital, Norway; Roche, France; and Roche, Norway.

Pain and bleeding associated with trephine biopsy.

The study objectives were to determine the intensity and duration of pain, factors that may influence pain experience during and after trephine biopsy, and to assess bleeding and infectious complications related to the procedure. Patients scheduled for trephine biopsy were recruited to the study. Local anesthesia was applied in all patients. Pain intensity was recorded twice daily by the patients using the numeric rating scale (NRS). Bleeding was graded into four grades. Median age of 184 patients was 63 yr. Maximum NRS level was measured at time of biopsy (T0); 167 (91%) patients experienced pain at T0. Median (Q1:Q3) NRS was 3 (1; 5). Median duration of pain was 36 h. Fourteen patients reported pain for more than 7 d. Significant inverse correlation was found between NRS at T0 and age. Pain duration at rest correlated with NRS at T0 and age, while pain duration in activity correlated with NRS at T0, age, and with body mass index (BMI). Mild and moderate bleeding at T0 occurred in 97 (54%) and 18 (10%) patients, respectively; no severe bleeding or infectious complications were registered. Secondary bleeding occurred in two patients; both required hospitalization. In conclusion, the study shows that despite the application of local anesthetic, more than 50% of the patients experienced pain of ≥ 3 points. Procedure-related bleeding is mild to moderate and managed by local pressure only.

Sustained cytogenetic response after discontinuation of imatinib mesylate in a patient with chronic myeloid leukaemia.

A 58-yr-old woman was diagnosed with Ph(+) chronic myeloid leukaemia in May 2001. She was initially treated with hydroxyurea and subsequently with interferon-alpha (IFN-alpha). Imatinib mesylate was started in April 2002 after failure of IFN-alpha to induce a cytogenetic response. The patient remained on treatment with imatinib mesylate for 3 months during which she suffered daily fever resulting in discontinuation of the treatment. Response evaluation performed shortly after discontinuing imatinib mesylate revealed a complete cytogenetic remission and a substantial molecular response. Fifteen months later, she was still enjoying a major cytogenetic response. This case illustrates that a short course of imatinib mesylate may result in a sustained haematological and cytogenetic response.