André Efira

Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment.

To evaluate the survival of patients with sickle cell disease (SCD) recorded in the Belgian SCD Registry and to assess the impact of disease‐modifying treatments (DMT).

Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients with lower risk myelodysplastic syndromes

BACKGROUND Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of iron overload and associated organ damage, and death. Emerging evidence indicates that iron chelation therapy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especially those classified as International Prognostic Scoring System (IPSS) Low or Intermediate-1 (Low/Int-1). METHODS Follow-up of a retrospective study. Sample included 127 Low/Int-1 MDS patients from 28 centers in Belgium. Statistical analysis stratified by duration (≥6 versus <6 months) and quality of chelation (adequate versus weak). RESULTS Crude chelation rate was 63% but 88% among patients with serum ferritin ≥1000 μg/L. Of the 80 chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox following deferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patients chelated ≥6 m, and 30% among patients chelated adequately; with a trend toward reduced cardiac mortality in chelated patients. Overall, median overall survival (OS) was 10.2 years for chelated and 3.1 years for non-chelated patients (p<0.001). For patients chelated ≥6 m or patients classified as adequately chelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusion intensity (HR=1.08, p=0.04) but was lower in patients receiving adequate chelation or chelation ≥6 m (HR=0.24, p<0.001). CONCLUSION Six or more months of adequate ICT is associated with markedly better overall survival. This suggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS.

Transfusion support of autoimmune hemolytic anemia: how could the blood group genotyping help?

Conventional pretransfusion testing based on hemagglutination assays can be challenging for patients with autoimmune hemolytic anemia (AIHA) because of the presence of auto-antibodies. It has been suggested that deoxyribonucleic acid-based methods could be more efficient in the selection of antigen-matched red blood cell units in those settings. Because of the high risk of alloimmunization of these patients and the labor-intensive nature of adsorption techniques, we decided to evaluate the feasibility of selecting antigen-matched units on the basis of RBC genotyping. We included in our routine RBC genotyping program samples from 7 patients with AIHA presenting a strongly positive direct antiglobulin test. This made the routine compatibility tests difficult. Most patients had previously received transfusions because of warm AIHA. Matched donor units were selected according to the genotype. For all but 1 patient, blood group genotyping could be done on time to allow antigen-matched transfusion. Four patients received antigen-matched red blood cell units based on RBC genotyping and for 1 patient the fact that no matched units were available led us to postpone the transfusion. After each transfusion, the recovery was recorded and considered satisfactory for all transfused patients.

Effect of N-acetylcysteine on pain in daily life in patients with sickle cell disease: a randomised clinical trial

N.J.S. collected and analysed the data and wrote the manuscript; H.K. designed the study and treated patients; E.J., J.E.C, D.A.T, M.E.R., N.D., Y.A., M.K., P.K., W.G.W. and C.D.D. treated patients; C.B., D.M. and M.A.R. collected and analysed the data; F.R. designed the study, collected and analysed the data, treated patients and wrote the manuscript. All authors approved the final version of the manuscript.

The light chain IgLV3-21 defines a new poor prognostic subgroup in Chronic Lymphocytic Leukemia: results of a multicenter study

Purpose: Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL) patients. Interestingly, IgHV3-21 is often co-expressed with light chain IgLV3-21, which is potentially able to trigger cell-autonomous BCR-mediated signaling. However, this light chain has never been characterized independently of the heavy chain IgHV3-21. Experimental Design: We performed total RNA sequencing in 32 patients and investigated IgLV3-21 prognostic impact in terms of treatment-free survival (TFS) and overall survival (OS) in 3 other independent cohorts for a total of 813 patients. IgLV3-21 presence was tested by real-time PCR and confirmed by Sanger sequencing. Results: Using total RNA sequencing to characterize 32 patients with high-risk CLL, we found a high frequency (28%) of IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these patients express higher levels of genes responsible for ribosome biogenesis and translation initiation (P < 0.0001) as well as MYC target genes (P = 0.0003). Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and OS (P < 0.05), particularly those with IgHV mutation. In each of the three independent validation cohorts, we showed that IgLV3-21 rearrangements—similar to UM IgHV status—conferred poor prognosis compared with mutated IgHV (P < 0.0001). Importantly, we confirmed by multivariate analysis that this was independent of IgHV mutational status or subset #2 stereotyped receptor (P < 0.0001). Conclusions: We have demonstrated for the first time that a light chain can affect CLL prognosis and that IgLV3-21 light chain usage defines a new subgroup of CLL patients with poor prognosis. Clin Cancer Res; 24(20); 5048–57. ©2018 AACR.

Added value of speckle tracking in the evaluation of cardiac function in patients with sickle cell disease

Speckle tracking echocardiography is a new means of evaluating cardiac function. The principle of speckle tracking is to measure myocardial strain, based on local shortening, lengthening and thickening of the muscles. It has been proposed that the left ventricle global longitudinal strain (LV-GLS) could be a useful tool for the detection of early systolic dysfunction in patients under cardiotoxic chemotherapy (Thavendiranathan et al, 2014). Moreover, the high reproducibility of the LV-GLS represents an advantage over the left ventricle ejection fraction (LVEF) (King et al, 2016; Medvedofsky et al, 2017). Compared to the LVEF, the LV-GLS is less affected by changes in loading conditions, which makes it a potentially useful tool in patients with sickle cell disease (SCD), due to the chronic overload associated with SCD. However, in this population, studies are rare and results are conflicting (Ahmad et al, 2012; Sengupta et al, 2012; Barbosa et al, 2014; Hammoudi et al, 2014). The primary aim of our study was to determine whether the LV-GLS was abnormal in a monocentric population of adults with SCD, compared to a matched population of healthy individuals. The secondary aim was to investigate correlations between the echocardiographic parameters and the biological and clinical evaluations of patients with SCD. The institutional Ethics Committee approved the protocol. All patients provided informed consent. We prospectively included 37 patients with SCD and 34 healthy, ageand sex-matched controls. The patient and control groups were similar in age (31 10 years vs. 32 10 years, respectively). The LVEF was significantly lower in the SCD group than in the control group (Teicholz: 61 8% vs. 67 6%; P = 0 05; Simpson: 61 9% vs. 69 3%; P < 0 05; Table I). However, only one patient had a Simpson LVEF < 50%. The left ventricular (LV) mass and LV end diastolic diameter (LVEDD) were higher in the patient group (LV mass: 107 g/m vs. 70 g/m, P < 0 05 and LVEDD: 53 mm vs. 46 mm; P < 0 05). The myocardial performance index was higher (higher values indicate impaired LV function) in the patient group compared to the control group (0 38 vs. 0 27; P < 0 05). The LV-GLS was significantly lower in the SCD group than in the control group ( 19 4% vs. 22 4%; P < 0 05), and it was abnormal (strain > 18%) in 8 (21%) patients of the SCD group. Diastolic function was abnormal in three SCD patients (8%), but normal in the entire control group. The tricuspid regurgitation velocity was higher in the SCD group than in the control group (2 24 m/s vs. 1 96 m/s, P < 0 05). However, no patient had pulmonary hypertension. The multivariate analysis results (Table II) showed that only the LV-GLS and LVEDD remained significantly different between groups. Among patients with SCD, the mean Hb was 94 g/l (range: 61–122 g/l) and the mean HbF was 12 7% (range: 1– 28 6%). The mean ferritin level was 644 lg/l (range: 13– 7267 lg/l). Iron overload, defined as a ferritin level greater than 1000 lg/l, was observed in five patients. The mean Nterminal pro b-type natriuretic peptide (NTproBNP) level was 154 pg/ml (range 12–1685 pg/ml). The mean patient walking distance was 66% of the predicted value (range: 33–88%).

Randomized phase II study of combined infusional leucovorin sodium (LVNa) and 5-FU versus the sequential administration of leucovorin calcium (LVCa) followed by 5-FU with irinotecan or oxaliplatin in patients (pts) with metastatic colorectal cancer (mCRC).

e14019 Background: 5-FU modulated by leucovorin calcium (LVCa) remains the mainstay of therapy for CRC. It is expected that LV Sodium (LVNa), which is stable when given with continuous infusion (ci) of 5-FU, could further enhance its activity. Methods: Eligibility criteria include confirmed mCRC, unresectable metastases, no previous chemotherapy, age ≥ 18 years, WHO-PS: ≤2. Pts received irinotecan 180 mg/m2 IV/30-90 min or oxaliplatin 100 mg/m2 IV/120 min and were randomized for LVCa 400 mg/m2/2 hours, followed by 5-FU bolus 400 mg/m2, and by 5-FU 3,000 mg/m2 IV ci/46 hours or, LVNa 400 mg/m2 plus 5-FU 3,000 mg/m2, IV ci/46 hours. Primary endpoint was objective response rate (ORR) by investigators and independent panel and assessed on pts who had a baseline and at least one post-baseline evaluations. Main secondary endpoints included safety, and overall/progression-free survival (OS, PFS) based on all pts treated. Experimental treatment was defined as warranting further evaluation in phase III if true ORR...

[Comparative study of 2 common tests for lupus anticoagulant determination: critical analysis of the results observed in 21 patients].

The Schleider and/or the Exner test have been found positive in twenty-one patients; five of these patients suffered of systemic lupus erythematosus (SLE). The Quick time and the activated partial thromboplastin time are normal in 52% of the cases. 40% have a minor haemorrhagic diathesis, without other significant clotting defect and 30% have thrombo-embolic complications. The Schleider index is more often strongly positive (greater than 2) in these two groups. 58% have an anemia, 25% a mild thrombocytopenia not deep enough to explain an haemorrhagic tendency (from 90.000 to 140.000/mm3). Several auto-immune tests are frequently positive even without SLE. The Schleider test is positive in 86% of the cases and appears a little more useful for the diagnosis than the Exner test, which has a 71% positivity.