Emmanuelle Bourgeois

Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura - results of a prospective multicenter phase 2 study

Whether rituximab could effectively and safely avoid splenectomy for adults with chronic immune thrombocytopenic purpura (ITP) remains unresolved. A multicenter, prospective, open-label, single-arm, phase 2 trial was conducted to assess rituximab safety and efficacy in adult splenectomy candidates with chronic ITP. Sixty patients with chronic (>or= 6 months) ITP and platelet counts less than 30 x 10(9)/L received a weekly intravenous infusion of rituximab (375 mg/m(2)) for 4 weeks. All other ITP treatments were stopped. A good response was defined as a platelet count 50 x 10(9)/L or more, with at least a doubling of the initial value at 1 and 2 years after the first rituximab infusion. Patients who required another treatment during follow up were considered nonresponders. Sixteen patients experienced transient side effects that necessitated treatment discontinuation for only 1. Good 1-year responses were obtained in 40% of the patients (24/60 [95% confidence interval: 28%-52%]). At 2 years, 33.3% (20/60 patients) had good responses and 6.7% (4/60) had sustained platelet counts of 30 x 10(9)/L or more without treatment. Thirty-six (60%) patients failed to respond; 25 underwent splenectomy. Based on these results, rituximab was an apparently safe and effective splenectomy-avoiding option in some adults with chronic ITP. This trial is registered at http://clinicaltrials.gov as NCT00225875.

Long‐term follow‐up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis

Summary. Splenectomy remains the most effective treatment of chronic autoimmune idiopathic thrombocytopenia (ITP) (i.e. of > 6 months duration). Treatment of patients refractory to splenectomy (with absence of response or relapse after initial response) is difficult, and their long‐term outcome is not well known. Over a 10‐year period, 183 patients with chronic ITP were splenectomized including 158 adults and 25 children (≤ 15 years). Forty‐seven of them, who were refractory to this treatment, were prospectively followed up for 5‐‐15 years (median 7·5 years). Twelve of them, with moderate thrombocytopenia, remained untreated, and 35 were treated by a median of two regimens (range 1‐‐6), to which 27 responded. Thirty‐six (77%) of the refractory cases reached platelet counts durably > 100 × 109/l, nine of them without treatment and 27 of them with low‐dose steroids or azathioprine; six (13%) remained moderately thrombocytopenic (35 × 109/l to 100 × 109/l platelets); the last five patients, without response to any treatment (up to six regimens), remained severely thrombocytopenic (platelets < 20 × 109/l), and three of them died from bleeding. Twenty‐seven (57%) of the 47 refractory cases required at least one hospitalization, in the majority of cases for intravenous immunoglobulin (IVIg) infusions. Seven of the refractory cases occurred in children. Six of them subsequently reached platelet counts > 100 × 109/l, but one died from bleeding. Our findings confirm the overall favourable long‐term prognosis of chronic ITP refractory to splenectomy.

Liver iron content assessment by routine and simple magnetic resonance imaging procedure in highly transfused patients.

Abstract:  Background: Liver iron content (LIC) assessment by magnetic resonance imaging (MRI) is validated but not standardized. In a single center, we tried to assess the accuracy of a specific, simple MRI procedure adapted to high LIC from a well‐established simple and routine procedure known to quantify LIC. Methods: In 27 cases of monthly transfused patients, we compared biochemical values of LIC assessed on liver biopsy specimens and results obtained by two signal intensity ratio of gradient echo imaging (R2*) MRI protocols. The first was Gandons routine procedure previously validated in liver disease and the second, our own method, was an addition of a gradient echo sequence specifically adapted to high LIC encountered in hematology practice. Results: Twenty‐seven liver biopsies were performed in 18 adult patients (myelodysplastic syndrome = 5, β‐thalassemia = 13). LIC by biopsy ranged from 1.4 to 54 mg/g liver dry weight (mg/g dw) (median 9.4 mg/g dw). Correlation between LIC by biopsy and by MRI with Gandons procedure was good (R = 0.80) in patients with LIC falling within the range reported by Gandon. By contrast, a weak correlation was demonstrated (R = 0.52) in patients with high LIC (above 11.2 mg/g dw). With our sequences, the correlation was good both in the entire group of patients (R = 0.83) and in patients with LIC above 11.2 mg/g dw (R = 0.85). Conclusion: Our results suggest that the addition of a specific shorter‐gradient echo sequence to a very simple, fast technique produces an accurate estimation of LIC in post‐transfusional iron overload.

Identification of a New Mutation on the β-Globin Gene: Codons 8/9 (+AGAA); GAG.AAG.TCT(Glu-Lys-Ser)>GAG. AAAGAAG, in a Patient From the North of France with a Phenotype of β-Thalassemia Minor

A 37-year-old man presented a slight debility. The hemogram showed a phenotype of β-thalassemia minor: Hb (13.1 g/dL), mean corpuscular volume (MCV) (62 fL) with low mean corpuscular hemoglobin (MCH) (20.8 pg), associated with a high level of Hb A2 of 5.3%. The serum ferritin level was 1,072 ng/mL. The sequencing of the mutated fragment revealed a duplication of four bases of codons 7/8 involving a shift in the open reading frame starting from codon 9 with a TGA stop codon at codon 23: codons 7/8/9 (+AGAA); GAG.AAG.TCT(Gly-Lys-Ser)>GAG.AAAGAAG. The human hemoglobin (Hb) instability tests were negative. The patient did not present the high iron Fe (HFE) mutation (C282Y, H63D). The same mutation was found in five other unrelated families (representing a total of 23 patients). All of their ancestors came from the north of France. This mutation has not been described before and could have its origins in the native populations of Northern France.