HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) inclu... more HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) including acute chest syndromes in adults, adolescents and children older than 2 years with sickle-cell disease (SCD). However, based on US and European expert panel recommendations (Yawn 2014, Habibi 2015) and results from placebo-controlled clinical trials, HU could be useful in SCD patients with severe anemia without VOC since it has been demonstrated to increase total Hb level (Wang 2011) and to decrease the need for blood transfusion. We hereby present preliminary results on effectiveness and safety data related to the prescription of HU for anemia from ESCORT-HU (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study designed to collect long-term safety data on HU in SCD population. Between January 2009 and June 2017, 1841 patients were enrolled from 63 centers in France, Germany, Greece and Italy, amongst which 126 patients (6...
BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 fo... more BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and approved since 2007 in the European Union (EU) and 2017 in the Unites States of America (USA) for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle cell disease (SCD). One risk raised for using a cytotoxic drug such as HU in children would be a potential negative impact on growth. Hence, a continuous follow-up of the growth of children treated with HU is recommended. We hypothesized that as HU increased hemoglobin concentration and enhances quality of life it may have a positive impact on growth and even more significantly improve growth and nutritional status in SCD children, who are exposed by their disease to impaired growth due to higher metabolic rate, chronic anemia, and hypoxemia. Here, we present preliminary results on growth development of sickle cell (SC) children enrolled in the ESCORT-HU study (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study whose objective is to evaluate the safety of HU in real life. METHOD Between January 2009 and June 2017, 1920 patients were enrolled from 63 centers in France, Germany, Greece and Italy. Of these 1920 patients, 849 (408 girls and 441 boys) were < 18 years of age. Patients' follow-up in ESCORT-HU is strictly observational and follows usual recommendations and local clinical practices. Patients are seen by their physician approximately every 3 to 6 months. Weights, heights and Body Mass Index (BMI) were thus collected all along the study. Patients previously treated with HU and HU-naïve before inclusion have been included in ESCORT-HU study which allowed comparison of these two groups of patients at inclusion in the study. The French population reference measurement scale (growth curve AFPA -CRESS/INSERM) was used for comparison of growth in children enrolled in ESCORT-HU as approximately 83% of children were included in France. RESULTS 547 children with reported height and/or weight were HU-naive at inclusion and 292 children were non-HU naive. Non-HU naïve patients had been treated for a median of 4.56 ± 3.29 years before inclusion in the ESCORT-HU cohort. Median duration of observation in the ESCORT-HU study was 2.60 ± 1.67 years Data on HU treatment and SC genotypes (90% SS) are displayed in table 1. Both heights and weights between HU-naive and non-HU naive girls and boys at enrolment were significantly different (p<0.001) (table 2 and 3). Non-HU naive girls and boys were taller and heavier compared to HU-naive patients, suggesting a positive impact of HU on growth. Mean heights and weights per age for girls were within the normal range all along the study with a mild decrease between 12 and 14 years old (Figure 1 and 2). For boys, weights and heights were within the normal range until the age of 11 and below the median normal range after 11 years (Figure 3 and 4). Mean BMIs stayed within the normal range for all age groups (Figure 5 and 6) during the course of treatment with HU. 12% of HU naive patients had a low BMI at enrolment but this percentage decreased constantly all along HU treatment (7.2% at year 2 and 3% at year 5). On the contrary, 6% of the patient were overweight (BMI above the normal range) and this percentage increased all along HU treatment (9.9% at year 2 and 15.8% at year 5). Among overweight patients, only seven were reported to have obesity and the percentage remained stable. CONCLUSION In the ESCORT-HU study children who were non HU-naive at enrolment were heavier and taller than HU-naive patients, but these differences faded during the course of HU treatment which confirmed the absence of negative impact of HU on growth. Heights and weights were within the normal range for girls whereas boys seemed to have a slower growth from 12 years of age. This difference may be due to pubertal delay in boys, but pubertal status was not collected in ESCORT-HU so this data could not be analysed. A minority of pediatric patients experienced overweight, suggesting to screen this possible complication. Disclosures Oevermann: Addmedica: Membership on an entity's Board of Directors or advisory committees. De Montalembert:Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. Brousse:Addmedica: Membership on an entity's Board of Directors or advisory committees. Pondarré:Blue Bird Bio: Honoraria; Novartis: Honoraria; Addmedica: Membership on an entity's Board of Directors or advisory committees.
INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and effi... more INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and efficacy of varicella post-exposure prophylaxis (PEP) recommendations. It was an observational, prospective, multicenter study set in Ile-de-France, France. METHODS All children under 18 with a cancer diagnosis, currently or within 3months of receiving cancer treatment, regardless of varicella zoster virus (VZV) serostatus or previous personal history of varicella, were eligible. Study participants with significant exposure were reviewed prospectively for PEP indications. Main outcome measures were the percentage of exposure situations for which HCP were guideline-compliant, the proportion of available VZV serostatuses and the incidence of breakthrough varicella after different PEP approaches. RESULTS A total of 51 patients from 15 centers were enrolled after 52 exposure episodes. Median age at exposure was 5 years (range, 1-15). Exposure within the household led to 38% of episodes. Prophylactic treatment consisted in specific anti-VZV immunoglobulins (V-ZIG) (n=19) or in oral aciclovir (n=15). No prophylactic treatment was given for 18 patients (in compliance, n=16). In compliance with guidelines, 17 patients received V-ZIG, 11 did not develop varicella (65%, [95% CI, 39-90%]); 15 received aciclovir, 13 did not develop varicella (87%, [95% CI, 67-100%]). Breakthrough varicella occurred in 11 patients, with simple clinical course in all cases; in 8/47 (17%) episodes when PEP was guideline-compliant versus 3/5 (60%) when not. DISCUSSION Recommendations have been respected and are efficient. PEP needs to be standardized and a study carried out to define the optimal approach. Anti-VZV immunization of seronegative family members should be encouraged.
HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) inclu... more HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) including acute chest syndromes in adults, adolescents and children older than 2 years with sickle-cell disease (SCD). However, based on US and European expert panel recommendations (Yawn 2014, Habibi 2015) and results from placebo-controlled clinical trials, HU could be useful in SCD patients with severe anemia without VOC since it has been demonstrated to increase total Hb level (Wang 2011) and to decrease the need for blood transfusion. We hereby present preliminary results on effectiveness and safety data related to the prescription of HU for anemia from ESCORT-HU (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study designed to collect long-term safety data on HU in SCD population. Between January 2009 and June 2017, 1841 patients were enrolled from 63 centers in France, Germany, Greece and Italy, amongst which 126 patients (6.8%) were started on HU for anemia from 34 centers. Of these 126, 96 were HU-naive. These HU-naive patients treated for anemia ('anemic' subpopulation) were selected for analysis to evaluate effectiveness and safety of HU in this indication and compared with data in HU-naive patients treated for other SCD indications. Demographic data and Hb genotypes are displayed in Table 1. The mean age, distribution of gender, Hb genotype and the mean HU dose at initiation were comparable in the 'anemic' subpopulation and the 'non-anemic' HU-naive cohort. Not surprisingly, mean Hb level at initiation was markedly lower in the 'anemic' subpopulation (7.07 ± 0.88 g/dl) than in the 'non-anemic' HU-naive cohort (8.71 ± 1.51 g/dl), with a lower proportion of patients with history of VOC and SCD-related hospitalization prior to HU initiation. The mean HU dose after 6 months was comparable in both groups (15.6 ± 3.83 mg/kg/day and 15.4 ± 4.11 mg/kg/day, respectively). Variation of blood parameters are displayed in Table 2. Similarly to what has been observed previously, a dramatic rise in Hb concentration (> 2 g/dl) was observed. This increase was comparable in absolute value to the increase observed in non-anemic patients. An increase in HbF was observed in the "anemic" subpopulation, with a near 2-fold increase in %HbF, markedly in children. Changes in reticulocyte counts were inconclusive due to small number of patients in the dataset. Safety of HU in the population of patients treated for anemia was evaluated by comparing incidence rates of non-SCD related adverse events (AEs) in HU-naive patients treated for anemia with the 'non-anemic' HU-naive ESCORT-HU subpopulation (Table 3). With mean follow-up periods of 18.3 months in 'anemic' subpopulation and 34.2 months in 'non-anemic' HU-naive cohort, preliminary results showed no striking difference in the incidence rate of reported AEs (total and serious) between the two populations (112.5% vs 139.8%, respectively for incidence rate of total AEs), and in the distribution of AEs by System Organ Class (SOC), at least in SOC where the number of adverse events was large enough to allow for comparison between the groups. Similarly, when focusing on AE causally related to HU (as judged by the investigators), the most frequently reported toxicity in the 'anemic' population was myelosuppression (anemia, neutropenia thrombocytopenia, pancytopenia reported in 4 children, one event each), as in the 'non-anemic' HU-naive cohort, with comparable incidence rates. In conclusion, even though HU is not licensed in Europe in severe chronic anemia, European and US expert panel guidelines recommend treatment with HU in this indication. Data from ESCORT-HU observational study on a subset of SCD patients treated off label in this indication confirmed total Hb level increase while the safety profile of HU in this subpopulation did not differ significantly from the 'non-anemic' HU-naive population. Disclosures De Montalembert: Novartis: Consultancy, Honoraria, Research Funding; Addmedica: Consultancy, Honoraria, Research Funding. Brousse: Add Medica: Membership on an entity's Board of Directors or advisory committees. Galacteros: Addmedica: Membership on an entity's Board of Directors or advisory committees.
SummaryDelayed haemolytic transfusion reaction (DHTR) is a life‐threatening haemolytic anaemia fo... more SummaryDelayed haemolytic transfusion reaction (DHTR) is a life‐threatening haemolytic anaemia following red blood cell transfusion in patients with sickle cell disease, with only scarce data in children. We retrospectively analysed 41 cases of DHTR in children treated between 2006 and 2020 in a French university hospital. DHTR manifested at a median age of 10.5 years, symptoms occurred a median of 8 days after transfusion performed for an acute event (63%), before surgery (20%) or in a chronic transfusion programme (17%). In all, 93% of patients had painful crisis. Profound anaemia (median 49 g/L), low reticulocyte count (median 140 ×109/L) and increased lactate dehydrogenase (median 2239 IU/L) were observed. Antibody screening was positive in 51% of patients, and more frequent when there was a history of alloimmunisation. Although no deaths were reported, significant complications occurred in 51% of patients: acute chest syndrome (12 patients), cholestasis (five patients), stroke ...
INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and effi... more INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and efficacy of varicella post-exposure prophylaxis (PEP) recommendations. It was an observational, prospective, multicenter study set in Ile-de-France, France. METHODS All children under 18 with a cancer diagnosis, currently or within 3months of receiving cancer treatment, regardless of varicella zoster virus (VZV) serostatus or previous personal history of varicella, were eligible. Study participants with significant exposure were reviewed prospectively for PEP indications. Main outcome measures were the percentage of exposure situations for which HCP were guideline-compliant, the proportion of available VZV serostatuses and the incidence of breakthrough varicella after different PEP approaches. RESULTS A total of 51 patients from 15 centers were enrolled after 52 exposure episodes. Median age at exposure was 5 years (range, 1-15). Exposure within the household led to 38% of episodes. Prophylactic treatment consisted in specific anti-VZV immunoglobulins (V-ZIG) (n=19) or in oral aciclovir (n=15). No prophylactic treatment was given for 18 patients (in compliance, n=16). In compliance with guidelines, 17 patients received V-ZIG, 11 did not develop varicella (65%, [95% CI, 39-90%]); 15 received aciclovir, 13 did not develop varicella (87%, [95% CI, 67-100%]). Breakthrough varicella occurred in 11 patients, with simple clinical course in all cases; in 8/47 (17%) episodes when PEP was guideline-compliant versus 3/5 (60%) when not. DISCUSSION Recommendations have been respected and are efficient. PEP needs to be standardized and a study carried out to define the optimal approach. Anti-VZV immunization of seronegative family members should be encouraged.
Background: Several controlled studies had established hydroxycarbamide as a gold standard for tr... more Background: Several controlled studies had established hydroxycarbamide as a gold standard for treatment of children affected with sickle cell disease. The European Sickle Cell Disease Cohort - Hydroxyurea (ESCORT-HU) is a cohort study designed to monitor in a large number of patients over a long period of time the use of hydroxycarbamide in current practice. Here we present the results on the paediatric cohort. Methods: Children were enrolled between January 2009 and June 2017. Patients were followed-up according to usual clinical monitoring. Efficacy was studied in a subpopulation naive for the treatment at enrolment, by comparing changes in Hb and HbF% levels, and in clinical outcomes after 12 months of treatment. Safety was assessed from the occurrence of adverse events in the total cohort. Findings: Eight hundred and twelve children (10.1 ± 2.3 years) have been enrolled; of these 141 were naive to the treatment. Median duration of follow-up for the whole cohort was 29 months (0...
BackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasm... more BackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.R...
BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 fo... more BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and approved since 2007 in the European Union (EU) and 2017 in the Unites States of America (USA) for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle cell disease (SCD). One risk raised for using a cytotoxic drug such as HU in children would be a potential negative impact on growth. Hence, a continuous follow-up of the growth of children treated with HU is recommended. We hypothesized that as HU increased hemoglobin concentration and enhances quality of life it may have a positive impact on growth and even more significantly improve growth and nutritional status in SCD children, who are exposed by their disease to impaired growth due to higher metabolic rate, chronic anemia, and hypoxemia. Here, we present preliminary results on growth development of sickle...
This study’s objective was to assess, on a national scale, residual risks of death, major disease... more This study’s objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006–2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival...
BACKGROUNDTransfusion‐transmitted bacterial infection (TTBI) is still one of the most feared comp... more BACKGROUNDTransfusion‐transmitted bacterial infection (TTBI) is still one of the most feared complications of blood transfusion.CASE REPORTWe report a fatal case involving an 8‐year‐old child with congenital dyskeratosis complicated by severe aplastic anemia who was regularly transfused with platelet (PLT) concentrates for 5 years. The patient received an apheresis PLT concentrate (APC) on Day 0 due to thrombocytopenia complicated by mucocutaneous hemorrhage. Thirty minutes after the start of the transfusion, bradycardia and dyspnea appeared, quickly followed by chills, nausea, vomiting, headache, and hyperthermia. TTBI was suspected and the patient was immediately treated with intravascular antibiotherapy. On Day 3, the patient developed severe acute respiratory distress syndrome leading to death on Day 7. Patient blood cultures and APC cultures were both positive for Citrobacter koseri.RESULTSThe donor was a 19‐year‐old woman. She had previously given blood. No infectious symptom ...
SummaryWe conducted a retrospective study on newborns with sickle‐cell disease (SCD), born 1995–2... more SummaryWe conducted a retrospective study on newborns with sickle‐cell disease (SCD), born 1995–2009, followed in a multicentre hospital‐based network. We assessed patient outcomes, medical care and compliance with the national guidelines published in December 2005. Data from 1033 patients (742 SS/Sβ°‐thalassaemia) with 6776 patient‐years of follow‐up were analysed (mean age 7·1 ± 3·9 years). SCD‐related deaths (n = 13) occurred only in SS‐genotype patients at a median age of 23·1 months, mainly due to acute anaemia (n = 5, including 2 acute splenic sequestrations) and infection (n = 3). Treatment non‐compliance was associated with a 10‐fold higher risk of SCD‐related death (P = 0·01). Therapeutic intensification was provided for all stroke patients (n = 12), almost all patients with abnormal transcranial Doppler (TCD) (n = 76) or with >1 acute chest syndrome/lifetime (n = 64) and/or ≥3 severe vaso‐occlusive crises/year (n = 100). Only 2/3 of patients with baseline haemoglobin &l...
HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) inclu... more HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) including acute chest syndromes in adults, adolescents and children older than 2 years with sickle-cell disease (SCD). However, based on US and European expert panel recommendations (Yawn 2014, Habibi 2015) and results from placebo-controlled clinical trials, HU could be useful in SCD patients with severe anemia without VOC since it has been demonstrated to increase total Hb level (Wang 2011) and to decrease the need for blood transfusion. We hereby present preliminary results on effectiveness and safety data related to the prescription of HU for anemia from ESCORT-HU (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study designed to collect long-term safety data on HU in SCD population. Between January 2009 and June 2017, 1841 patients were enrolled from 63 centers in France, Germany, Greece and Italy, amongst which 126 patients (6...
BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 fo... more BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and approved since 2007 in the European Union (EU) and 2017 in the Unites States of America (USA) for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle cell disease (SCD). One risk raised for using a cytotoxic drug such as HU in children would be a potential negative impact on growth. Hence, a continuous follow-up of the growth of children treated with HU is recommended. We hypothesized that as HU increased hemoglobin concentration and enhances quality of life it may have a positive impact on growth and even more significantly improve growth and nutritional status in SCD children, who are exposed by their disease to impaired growth due to higher metabolic rate, chronic anemia, and hypoxemia. Here, we present preliminary results on growth development of sickle cell (SC) children enrolled in the ESCORT-HU study (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study whose objective is to evaluate the safety of HU in real life. METHOD Between January 2009 and June 2017, 1920 patients were enrolled from 63 centers in France, Germany, Greece and Italy. Of these 1920 patients, 849 (408 girls and 441 boys) were &amp;amp;amp;lt; 18 years of age. Patients&amp;amp;#39; follow-up in ESCORT-HU is strictly observational and follows usual recommendations and local clinical practices. Patients are seen by their physician approximately every 3 to 6 months. Weights, heights and Body Mass Index (BMI) were thus collected all along the study. Patients previously treated with HU and HU-naïve before inclusion have been included in ESCORT-HU study which allowed comparison of these two groups of patients at inclusion in the study. The French population reference measurement scale (growth curve AFPA -CRESS/INSERM) was used for comparison of growth in children enrolled in ESCORT-HU as approximately 83% of children were included in France. RESULTS 547 children with reported height and/or weight were HU-naive at inclusion and 292 children were non-HU naive. Non-HU naïve patients had been treated for a median of 4.56 ± 3.29 years before inclusion in the ESCORT-HU cohort. Median duration of observation in the ESCORT-HU study was 2.60 ± 1.67 years Data on HU treatment and SC genotypes (90% SS) are displayed in table 1. Both heights and weights between HU-naive and non-HU naive girls and boys at enrolment were significantly different (p&amp;amp;amp;lt;0.001) (table 2 and 3). Non-HU naive girls and boys were taller and heavier compared to HU-naive patients, suggesting a positive impact of HU on growth. Mean heights and weights per age for girls were within the normal range all along the study with a mild decrease between 12 and 14 years old (Figure 1 and 2). For boys, weights and heights were within the normal range until the age of 11 and below the median normal range after 11 years (Figure 3 and 4). Mean BMIs stayed within the normal range for all age groups (Figure 5 and 6) during the course of treatment with HU. 12% of HU naive patients had a low BMI at enrolment but this percentage decreased constantly all along HU treatment (7.2% at year 2 and 3% at year 5). On the contrary, 6% of the patient were overweight (BMI above the normal range) and this percentage increased all along HU treatment (9.9% at year 2 and 15.8% at year 5). Among overweight patients, only seven were reported to have obesity and the percentage remained stable. CONCLUSION In the ESCORT-HU study children who were non HU-naive at enrolment were heavier and taller than HU-naive patients, but these differences faded during the course of HU treatment which confirmed the absence of negative impact of HU on growth. Heights and weights were within the normal range for girls whereas boys seemed to have a slower growth from 12 years of age. This difference may be due to pubertal delay in boys, but pubertal status was not collected in ESCORT-HU so this data could not be analysed. A minority of pediatric patients experienced overweight, suggesting to screen this possible complication. Disclosures Oevermann: Addmedica: Membership on an entity&amp;amp;#39;s Board of Directors or advisory committees. De Montalembert:Addmedica: Honoraria, Membership on an entity&amp;amp;#39;s Board of Directors or advisory committees; Novartis: Consultancy. Brousse:Addmedica: Membership on an entity&amp;amp;#39;s Board of Directors or advisory committees. Pondarré:Blue Bird Bio: Honoraria; Novartis: Honoraria; Addmedica: Membership on an entity&amp;amp;#39;s Board of Directors or advisory committees.
INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and effi... more INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and efficacy of varicella post-exposure prophylaxis (PEP) recommendations. It was an observational, prospective, multicenter study set in Ile-de-France, France. METHODS All children under 18 with a cancer diagnosis, currently or within 3months of receiving cancer treatment, regardless of varicella zoster virus (VZV) serostatus or previous personal history of varicella, were eligible. Study participants with significant exposure were reviewed prospectively for PEP indications. Main outcome measures were the percentage of exposure situations for which HCP were guideline-compliant, the proportion of available VZV serostatuses and the incidence of breakthrough varicella after different PEP approaches. RESULTS A total of 51 patients from 15 centers were enrolled after 52 exposure episodes. Median age at exposure was 5 years (range, 1-15). Exposure within the household led to 38% of episodes. Prophylactic treatment consisted in specific anti-VZV immunoglobulins (V-ZIG) (n=19) or in oral aciclovir (n=15). No prophylactic treatment was given for 18 patients (in compliance, n=16). In compliance with guidelines, 17 patients received V-ZIG, 11 did not develop varicella (65%, [95% CI, 39-90%]); 15 received aciclovir, 13 did not develop varicella (87%, [95% CI, 67-100%]). Breakthrough varicella occurred in 11 patients, with simple clinical course in all cases; in 8/47 (17%) episodes when PEP was guideline-compliant versus 3/5 (60%) when not. DISCUSSION Recommendations have been respected and are efficient. PEP needs to be standardized and a study carried out to define the optimal approach. Anti-VZV immunization of seronegative family members should be encouraged.
HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) inclu... more HU is licensed in Europe in the prevention of recurrent painful vaso-occlusive crises (VOC) including acute chest syndromes in adults, adolescents and children older than 2 years with sickle-cell disease (SCD). However, based on US and European expert panel recommendations (Yawn 2014, Habibi 2015) and results from placebo-controlled clinical trials, HU could be useful in SCD patients with severe anemia without VOC since it has been demonstrated to increase total Hb level (Wang 2011) and to decrease the need for blood transfusion. We hereby present preliminary results on effectiveness and safety data related to the prescription of HU for anemia from ESCORT-HU (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study designed to collect long-term safety data on HU in SCD population. Between January 2009 and June 2017, 1841 patients were enrolled from 63 centers in France, Germany, Greece and Italy, amongst which 126 patients (6.8%) were started on HU for anemia from 34 centers. Of these 126, 96 were HU-naive. These HU-naive patients treated for anemia ('anemic' subpopulation) were selected for analysis to evaluate effectiveness and safety of HU in this indication and compared with data in HU-naive patients treated for other SCD indications. Demographic data and Hb genotypes are displayed in Table 1. The mean age, distribution of gender, Hb genotype and the mean HU dose at initiation were comparable in the 'anemic' subpopulation and the 'non-anemic' HU-naive cohort. Not surprisingly, mean Hb level at initiation was markedly lower in the 'anemic' subpopulation (7.07 ± 0.88 g/dl) than in the 'non-anemic' HU-naive cohort (8.71 ± 1.51 g/dl), with a lower proportion of patients with history of VOC and SCD-related hospitalization prior to HU initiation. The mean HU dose after 6 months was comparable in both groups (15.6 ± 3.83 mg/kg/day and 15.4 ± 4.11 mg/kg/day, respectively). Variation of blood parameters are displayed in Table 2. Similarly to what has been observed previously, a dramatic rise in Hb concentration (&gt; 2 g/dl) was observed. This increase was comparable in absolute value to the increase observed in non-anemic patients. An increase in HbF was observed in the "anemic" subpopulation, with a near 2-fold increase in %HbF, markedly in children. Changes in reticulocyte counts were inconclusive due to small number of patients in the dataset. Safety of HU in the population of patients treated for anemia was evaluated by comparing incidence rates of non-SCD related adverse events (AEs) in HU-naive patients treated for anemia with the 'non-anemic' HU-naive ESCORT-HU subpopulation (Table 3). With mean follow-up periods of 18.3 months in 'anemic' subpopulation and 34.2 months in 'non-anemic' HU-naive cohort, preliminary results showed no striking difference in the incidence rate of reported AEs (total and serious) between the two populations (112.5% vs 139.8%, respectively for incidence rate of total AEs), and in the distribution of AEs by System Organ Class (SOC), at least in SOC where the number of adverse events was large enough to allow for comparison between the groups. Similarly, when focusing on AE causally related to HU (as judged by the investigators), the most frequently reported toxicity in the 'anemic' population was myelosuppression (anemia, neutropenia thrombocytopenia, pancytopenia reported in 4 children, one event each), as in the 'non-anemic' HU-naive cohort, with comparable incidence rates. In conclusion, even though HU is not licensed in Europe in severe chronic anemia, European and US expert panel guidelines recommend treatment with HU in this indication. Data from ESCORT-HU observational study on a subset of SCD patients treated off label in this indication confirmed total Hb level increase while the safety profile of HU in this subpopulation did not differ significantly from the 'non-anemic' HU-naive population. Disclosures De Montalembert: Novartis: Consultancy, Honoraria, Research Funding; Addmedica: Consultancy, Honoraria, Research Funding. Brousse: Add Medica: Membership on an entity's Board of Directors or advisory committees. Galacteros: Addmedica: Membership on an entity's Board of Directors or advisory committees.
SummaryDelayed haemolytic transfusion reaction (DHTR) is a life‐threatening haemolytic anaemia fo... more SummaryDelayed haemolytic transfusion reaction (DHTR) is a life‐threatening haemolytic anaemia following red blood cell transfusion in patients with sickle cell disease, with only scarce data in children. We retrospectively analysed 41 cases of DHTR in children treated between 2006 and 2020 in a French university hospital. DHTR manifested at a median age of 10.5 years, symptoms occurred a median of 8 days after transfusion performed for an acute event (63%), before surgery (20%) or in a chronic transfusion programme (17%). In all, 93% of patients had painful crisis. Profound anaemia (median 49 g/L), low reticulocyte count (median 140 ×109/L) and increased lactate dehydrogenase (median 2239 IU/L) were observed. Antibody screening was positive in 51% of patients, and more frequent when there was a history of alloimmunisation. Although no deaths were reported, significant complications occurred in 51% of patients: acute chest syndrome (12 patients), cholestasis (five patients), stroke ...
INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and effi... more INTRODUCTION The objective was to evaluate health care providers' (HCP) adherence to and efficacy of varicella post-exposure prophylaxis (PEP) recommendations. It was an observational, prospective, multicenter study set in Ile-de-France, France. METHODS All children under 18 with a cancer diagnosis, currently or within 3months of receiving cancer treatment, regardless of varicella zoster virus (VZV) serostatus or previous personal history of varicella, were eligible. Study participants with significant exposure were reviewed prospectively for PEP indications. Main outcome measures were the percentage of exposure situations for which HCP were guideline-compliant, the proportion of available VZV serostatuses and the incidence of breakthrough varicella after different PEP approaches. RESULTS A total of 51 patients from 15 centers were enrolled after 52 exposure episodes. Median age at exposure was 5 years (range, 1-15). Exposure within the household led to 38% of episodes. Prophylactic treatment consisted in specific anti-VZV immunoglobulins (V-ZIG) (n=19) or in oral aciclovir (n=15). No prophylactic treatment was given for 18 patients (in compliance, n=16). In compliance with guidelines, 17 patients received V-ZIG, 11 did not develop varicella (65%, [95% CI, 39-90%]); 15 received aciclovir, 13 did not develop varicella (87%, [95% CI, 67-100%]). Breakthrough varicella occurred in 11 patients, with simple clinical course in all cases; in 8/47 (17%) episodes when PEP was guideline-compliant versus 3/5 (60%) when not. DISCUSSION Recommendations have been respected and are efficient. PEP needs to be standardized and a study carried out to define the optimal approach. Anti-VZV immunization of seronegative family members should be encouraged.
Background: Several controlled studies had established hydroxycarbamide as a gold standard for tr... more Background: Several controlled studies had established hydroxycarbamide as a gold standard for treatment of children affected with sickle cell disease. The European Sickle Cell Disease Cohort - Hydroxyurea (ESCORT-HU) is a cohort study designed to monitor in a large number of patients over a long period of time the use of hydroxycarbamide in current practice. Here we present the results on the paediatric cohort. Methods: Children were enrolled between January 2009 and June 2017. Patients were followed-up according to usual clinical monitoring. Efficacy was studied in a subpopulation naive for the treatment at enrolment, by comparing changes in Hb and HbF% levels, and in clinical outcomes after 12 months of treatment. Safety was assessed from the occurrence of adverse events in the total cohort. Findings: Eight hundred and twelve children (10.1 ± 2.3 years) have been enrolled; of these 141 were naive to the treatment. Median duration of follow-up for the whole cohort was 29 months (0...
BackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasm... more BackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.R...
BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 fo... more BACKGROUND HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and approved since 2007 in the European Union (EU) and 2017 in the Unites States of America (USA) for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle cell disease (SCD). One risk raised for using a cytotoxic drug such as HU in children would be a potential negative impact on growth. Hence, a continuous follow-up of the growth of children treated with HU is recommended. We hypothesized that as HU increased hemoglobin concentration and enhances quality of life it may have a positive impact on growth and even more significantly improve growth and nutritional status in SCD children, who are exposed by their disease to impaired growth due to higher metabolic rate, chronic anemia, and hypoxemia. Here, we present preliminary results on growth development of sickle...
This study’s objective was to assess, on a national scale, residual risks of death, major disease... more This study’s objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006–2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival...
BACKGROUNDTransfusion‐transmitted bacterial infection (TTBI) is still one of the most feared comp... more BACKGROUNDTransfusion‐transmitted bacterial infection (TTBI) is still one of the most feared complications of blood transfusion.CASE REPORTWe report a fatal case involving an 8‐year‐old child with congenital dyskeratosis complicated by severe aplastic anemia who was regularly transfused with platelet (PLT) concentrates for 5 years. The patient received an apheresis PLT concentrate (APC) on Day 0 due to thrombocytopenia complicated by mucocutaneous hemorrhage. Thirty minutes after the start of the transfusion, bradycardia and dyspnea appeared, quickly followed by chills, nausea, vomiting, headache, and hyperthermia. TTBI was suspected and the patient was immediately treated with intravascular antibiotherapy. On Day 3, the patient developed severe acute respiratory distress syndrome leading to death on Day 7. Patient blood cultures and APC cultures were both positive for Citrobacter koseri.RESULTSThe donor was a 19‐year‐old woman. She had previously given blood. No infectious symptom ...
SummaryWe conducted a retrospective study on newborns with sickle‐cell disease (SCD), born 1995–2... more SummaryWe conducted a retrospective study on newborns with sickle‐cell disease (SCD), born 1995–2009, followed in a multicentre hospital‐based network. We assessed patient outcomes, medical care and compliance with the national guidelines published in December 2005. Data from 1033 patients (742 SS/Sβ°‐thalassaemia) with 6776 patient‐years of follow‐up were analysed (mean age 7·1 ± 3·9 years). SCD‐related deaths (n = 13) occurred only in SS‐genotype patients at a median age of 23·1 months, mainly due to acute anaemia (n = 5, including 2 acute splenic sequestrations) and infection (n = 3). Treatment non‐compliance was associated with a 10‐fold higher risk of SCD‐related death (P = 0·01). Therapeutic intensification was provided for all stroke patients (n = 12), almost all patients with abnormal transcranial Doppler (TCD) (n = 76) or with >1 acute chest syndrome/lifetime (n = 64) and/or ≥3 severe vaso‐occlusive crises/year (n = 100). Only 2/3 of patients with baseline haemoglobin &l...
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