Catherine Heijmans

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).

Haematopoietic stem cell transplantation for severe sickle cell disease in childhood: a single centre experience of 50 patients

Despite improvements in medical management, sickle cell disease (SCD) remains associated with severe morbidity and decreased survival. Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only curative approach. We report the outcome of 50 consecutive children with severe SCD that received HSCT in our unit between November 1988 and April 2013. The stem cell source was bone marrow (n = 39), cord blood (n = 3), bone marrow and cord blood (n = 7) and peripheral blood stem cells (n = 1). All patients had ≥1 severe manifestation: 37 presented with recurrent vaso‐occlusive crises/acute chest syndrome, 27 cerebral vasculopathy and 1 nephropathy. The conditioning regimen consisted of busulfan + cyclophosphamide (BuCy) before November 1991 and BuCy + rabbit antithymocyte globulin after that date. Since 1995, all patients have been treated with hydroxycarbamide (HC) prior to transplantation for a median duration of 2·7 years. Median age at transplantation and median follow‐up was 8·3 and 7·7 years, respectively. Acute graft‐versus‐host disease (GVHD) and chronic GVHD were observed in 11 and 10 patients, respectively. An excellent outcome was achieved, with 8‐year overall survival and event‐free survival (EFS) rates of 94·1% and 85·6%, respectively. Since HC introduction, no graft failure occurred and EFS reached 97·4%. Prior treatment with HC may have contributed to successful engraftment.

Use of hydroxyurea in prevention of stroke in children with sickle cell disease

To the editor: We carefully read the paper by Zimmerman and colleagues[1][1] about the possible effect of hydroxyurea on the transcranial doppler flow velocities in children with sickle cell disease. We reviewed the transcranial dopplers (TCD) performed on the children with sickle cell disease in

First Documented Transmission of Trypanosoma cruzi Infection through Blood Transfusion in a Child with Sickle-Cell Disease in Belgium.

The affiliation for the fifth author is incorrect. Hanane El Kenz is affiliated with Brugmann University Hospital Center and Queen Fabiola University Children Hospital Blood Bank Department, Brussels, Belgium.

Reduction of the Six-Minute Walk Distance in Children with Sickle Cell Disease Is Correlated with Silent Infarct: Results from a Cross-Sectional Evaluation in a Single Center in Belgium

Background The 6-minute walk test (6MWT) is used in adults and children affected by a wide range of chronic diseases to evaluate their sub-maximal exercise capacity. It reflects the global response of various physiological systems in a situation simulating a daily life activity. Methods We analyzed factors affecting the 6MWT in 46 Sickle Cell Disease children. Forty-two were treated with hydroxyurea (HU). Patients with normal test (>80% of the age-standardized predicted value) were compared to patients with abnormal test (≤80%). Baseline hematological values, clinical events, cerebrovascular disease, cardio-pulmonary parameters and disease-modifying treatment were compared according to the performance of the test. Results Among the 46 patients, 14 had an abnormal 6MWT. In univariate analysis, both groups were similar for biological and clinical data. Six of the 14 patients with an abnormal 6MWT had silent infarct (SI) compared to 6/32 with a normal test (P = 0.09). When excluding chronically transfused patients, 4 of the 11 patients with an abnormal 6MWT had SI compared to 1/26 (P = 0.02). Baseline pulse oximetry was normal in both groups but slightly lower in patients with abnormal 6MWT (P = 0.02). No patient presented exercise-induced desaturation. In multivariate analysis, the only factor associated with abnormal 6MWT was the presence of SI (P = 0.045). Conclusions In our cohort of 46 patients characterized by high exposure rate to HU and by the absence of severe cardiopulmonary disease, the sole factor independently associated with 6MWT was the presence of SI. The lower exercise capacity of children with SI may reflect some subclinical neurological impairment as they do not differ by hemoglobin level or cardiopulmonary parameters.

Neonatal screening improves sickle cell disease clinical outcome in Belgium.

Objectives To compare the outcomes of sickle cell disease patients diagnosed through neonatal screening with those who were not. Methods In an observational multicenter study in Belgium, 167 screened and 93 unscreened sickle cell disease patients were analyzed for a total of 1116 and 958 patient-years of follow-up, respectively. Both groups were compared with propensity score analysis, with patients matched on three covariates (gender, genotype, and central Africa origin). Bonferroni correction was applied for all comparisons. Results Kaplan–Meier estimates of survival without bacteremia were significantly higher in the screened group than the unscreened group (94.47%; [95% CI, 88.64–97.36%] versus 83.78% [95% CI, 72.27–90.42%]), p = 0.032. Non-significant differences between both groups were reported for survival without acute chest syndrome, acute anemia, cerebral complication, severe infection, and vaso-occlusive crisis. Significantly lower hospitalization rate and days per 100 patient-years were observed in the screened compared with the unscreened group (0.27 vs. 0.63 and 1.25 vs. 2.82, p = 0.0006 and <0.0001). Conclusion These data confirm the benefit of a neonatal screening programme in reducing bacteremia and hospitalization.

A pilot study of manual chronic partial exchange transfusion in children with sickle disease

Abstract Objective Red cell exchange transfusion is frequently used in the management of patients with sickle cell disease (SCD) either electively or chronically to maintain hemoglobin S (HbS) <30%. The purpose of this retrospective study was to evaluate the results of manual chronic partial exchange transfusion (MCPET) on level of Hb and HbS, on iron load and on the need for chelation, on risk of immunization, monitoring transfusion-transmitted viral infection, and clinical outcome. Methods We reviewed the long-term effect of MCPET in 10 children (six men and four women) with SCD and evaluated the iron balance during a median follow-up of 20 months (range: 6–36) in which 248 exchanges were performed. Results The pre-exchange median Hb value was 9.5 g/dl (range: 7.7–10.9 g/dl) and the median post-exchange value was 9.4 g/dl (range: 8.4–11.1 g/dl).The majority of patients reached an HbS of <50% with a median HbS value of 40.04% (range: 30–54). At start of the MCPET program, the median ferritin was 439 ng/ml (range: 80–1704 ng/ml). In the final evaluation, the median value of ferritin was 531 ng/ml (range: 84–3840 ng/ml). The annual calculated iron balance was 0. 28 ± 0.08 mg/kg/day. MCPET was well tolerated, and adverse effects were limited. Discussion MCPET in children with SCD is safe to prevent iron overload, and is effective and easy to use in our cohort. Conclusion Indication for chronic exchange blood transfusion is essential for patients with SCD with recurrent and frequent crises who do not respond to hydroxyurea. However, there is no consensual study for the period at which chronic transfusion can safely be stopped and further research in large population of patients with SCD will need to clarify this question.

Is Pica under-reported in children with sickle cell disease? A pilot study in a Belgian cohort

Abstract Background For centuries, writers have recorded their observations on pica. Nevertheless the association of pica with sickle cell disease (SCD) was poorly documented. Methods Cross-sectional evaluation performed on SCD children and caregivers attending the outpatient clinic who were invited to complete questionnaires assessing behavior of pica. Results Out of 55 sickle cell children, 31(56.4%) reported practicing pica regularly. Substances ingested by patients covered a broad spectrum. Compared with the non-pica group, subjects who reported pica were younger and had lower hemoglobin (8.3 g/dl (7.6–9.7) vs. 9.1 g/dl (7.9–10.5): P < 0.01). The level of ferritin, zinc, copper, and lead was similar between the pica and non-pica groups (P > 0.05). Discussion In this series, there are many substances consumed by SCD children and adolescents, and we did not find an occurrence of similar substances among this select group. Pica children were younger and more anemic than non-pica patients. Conclusion This study suggests that pica remains an unknown and under-reported clinical problem in children with SCD and seems to be related to the severity of anemia. The next step of this project aims to clarify causal mechanisms for pica and its association with SCD in a larger population.

Automated RBC exchange compared to manual exchange transfusion for children with sickle cell disease is cost-effective and reduces iron overload: THERAPEUTIC APHERESIS FOR SCD

Chronic transfusion in sickle cell disease (SCD) remains the gold standard therapy for stroke prevention and for patients with severe disease despite adequate hydroxyurea treatment. The aim of our study was to assess the safety and efficacy of automated red blood cell exchange (aRBX) in patients with SCD previously treated with manual exchange transfusion (MET). Costs related to transfusion and chelation overtime were evaluated.

1613 Management of Vaso-Occlusive Crisis with Patient Controlled Analgesia

Pain resulting from sickle-cell vaso-occlusive crisis (VOC) is often severe, prolonged and difficult to alleviate. Guidelines based on scientific evidence are lacking. In order to evaluate the effectiveness of our treatment protocol, we performed a population-based retrospective observational study on HbSS sickle-cell patients (n=22) admitted for severe VOC (n=48) during a 30-months period and managed with patient controlled analgesia (PCA). Median (10th-90th percentiles) visual analogical pain scale (VAS) at admission was 9.5(7–10). Patient received 0.3mg/kg (0.1–0.4) intravenous morphine at admission, then PCA was started with the following settings: continuous rate: 20 µg/kg/h (10–25), bolus: 25µg/kg (21–32), and 1.8 bolus allowed/hour (1.7–2.8). Six hours after admission, VAS was less than 7 in only 41% of cases. The median VAS declined steadily during hospitalization. Pain intensity was not correlated with morphine dosage. Success 6 hours after admission (VAS< 7) and during hospitalization (VAS£4) was associated with significantly lower VAS score at admission and lower number of VOC during the study period. Patients who experienced >2 CVO/year have the following characteristics: higher VAS at admission, higher morphine dosages, lower success rate and lower CRP, bilirubin, LDH and reticulocyte count. The difficulties encountered in the management of patients who experienced >2 VOC/year may be related to their genotypic particularities. For such patients, an increase of morphine dosage is required. We have developed a computer routine in order to reduce time and increase accuracy of PCA prescription, and to build a prospective database that enables continuous assessment of our treatment protocol.