Number Of Vaso-occlusive Crises Research Articles

Opioid Use After First Opioid Prescription in Children With Sickle Cell Disease

This cohort study assesses the level of opioid use, number of vaso-occlusive crises, and days’ supply of opioids among opioid-naive pediatric patients.

Real-world evidence of the burden of sickle cell disease: a 5-year longitudinal study at a Brazilian reference center

IntroductionSickle cell disease (SCD) is an inherited and multisystem blood disorder characterized by hemolytic anemia, vaso-occlusive crises (VOCs), progressive multiorgan damage and increased mortality. In Brazil, it is one of the most common monogenic diseases afflicting 60,000 to 100,000 individuals, however, there are sparse epidemiological data, as well as information on the utilization of public healthcare resources. Method: This was a 5-year (2016 - 2020) retrospective study conducted at one Brazilian reference center on SCD - Santa Casa de Sao Paulo, in Sao Paulo, Brazil. ResultsAmong a total of 100 eligible adult patients, the median age was 31.0 years old, 84% of the patients were aged between 18 and 45 years old; 59% were women and 91% presented the genotype HbSS. The number of hematologist and non-hematologist visits at the outpatient unit were 2,198 and 1,436, respectively. The number of hospital ER visits was 758, of which 51% required 864 days of hospitalization. The main cause for seeking hospital medical care was the VOCs. The numbers and ratios of VOCs were: 1 to 10 VOCs, 64%; 11 to 20, 15%, and; 21 or more, 1%. There was a statistically significant difference between the number of VOCs and hospitalizations, as well as infection. Conclusion: Results indicate the burden of SCD on Brazilian patients’ daily lives, the impact of VOCs on public healthcare resources, the importance of having a national surveillance program to improve resource utilization and clinical outcomes of patients with SCD and the urgent need for the revitalizing of the current national comprehensive SCD care programs.

Are Genetic Modifiers the Answer to Different Responses to Hydroxyurea Treatment?-A Pharmacogenetic Study in Sickle Cell Anemia Angolan Children.

Sickle cell anemia (SCA) is an inherited disease affecting the hemoglobin that is particularly common in sub-Saharan Africa. Although monogenic, phenotypes are markedly heterogeneous in terms of severity and life span. Hydroxyurea is still the most common treatment for these patients, and the response to treatment is highly variable and seems to be an inherited trait. Therefore, identifying the variants that might predict hydroxyurea response is important for identifying patients who will have a poorer or non-response to treatment, and the ones that are more prone to suffer from severe side effects. In the present pharmacogenetic study, we analyzed the exons of 77 genes described in the literature as potentially associated with hydroxyurea metabolism in Angolan children treated with hydroxyurea and evaluated the drug response considering fetal hemoglobin levels, other hematological and biochemical parameters, hemolysis, number of vaso-occlusive crises and hospitalizations. Thirty variants were identified in 18 of those genes as possibly associated with drug response, five of them in gene DCHS2. Other polymorphisms in this gene were also associated with hematological, biochemical and clinical parameters. Further research examining the maximum tolerated dose and fixed dose with a larger sample size is necessary to corroborate these findings.

PB2224: IMPACT OF COVID-19 PANDEMIC ON PATIENTS WITH SICKLE CELL DISEASE: RESULTS FROM THE REAL WORLD ASSESSMENT SURVEY FOR SICKLE CELL DISEASE IN SAUDI (ROARS)

Background: Sickle cell disease (SCD) is a chronic hemolytic disease with multisystem involvement leading to significant morbidities and mortalities. SCD confers a significant burden on patients (pts), including a high impact on quality of life (QoL). The impact of the COVID-19 pandemic on pts with SCD has not been well characterized. Aims: The Real World Assessment Survey for Sickle Cell Disease in the Kingdom of Saudi Arabia (KSA) (ROARS) is a cross-sectional survey of pts with SCD and treating healthcare professionals (HCPs), which was designed to understand several aspects of the burden of SCD in KSA. In this study, we examined the impact of the COVID-19 pandemic on SCD pts based on findings from ROARS. Methods: Between September and December 2021, pts with SCD (age: 5-65 years) and HCPs (>2 years SCD experience, SCD load >50 pts, >50% of clinical practice time spent treating SCD pts) were surveyed (in person or via caregiver if pts were between 5-14 years of age) using the structured, bilingual ROARS questionnaires (English/Arabic) through personal quantitative web-assisted telephone interviews. ROARS was developed by SCD experts from KSA and Novartis, and includes the global health domain of Patient-Reported Outcomes Measurement Information System (PROMIS), a validated tool for assessing QoL among SCD pts and caregivers of different age ranges. Questions covered topics such as disease impact on QoL, symptoms, disease complications, treatment goals, treatment strategies, and COVID-19. Descriptive statistics were used to summarize the results. Results: A total of 1011 pts (pediatric: n=504; adult: n=507) and 64 HCPs (hematologists: n=31; non-hematologists: n=33) completed the survey. Data were collected from 11 cities, with 90% of respondents from Eastern and South-Western provinces of KSA where the SCD prevalence is highest. The top 5 complications reported by both pediatric and adult pts were fever (52%), joint issues (49%), swollen and/or painful fingers/toes (47%), infections (37%), and tight chest pain (35%). A high proportion of pts (80%) felt that the pandemic had an impact on their medical care (Figure) (adults: 85%;[PM(1] pediatric: 76%). The impact of COVID-19 on medical care was particularly evident in pts treated with hydroxyurea compared to untreated pts (adults: 91% and 79%; pediatric: 84% and 74%). When survey results were stratified by the number of vaso-occlusive crises (VOCs), 85% of adult pts reported an impact of the pandemic on their medical care, regardless of the VOC frequency (<5 or ≥5); among pediatric pts, 72% with ≥5 VOCs and 83% with <5 VOCs reported an impact. Mental/emotional impact of the pandemic was reported by 66% of pts (adults: 68%; pediatric: 64%). The majority of pts missed or cancelled their appointments due to COVID-19 (adults: 81%; pediatric: 74%). Overall, 39% of the pts reported the impact of the pandemic as severe (Figure). From the HCPs’ perspective, 86% felt that COVID-19 affected their medical service, and 78% thought it affected their pts’ mental/emotional well-being. Overall, 16% of HCPs thought the pandemic significantly impacted their pts. Image:Summary/Conclusion: The ROARS survey among Saudi pts with SCD found that the majority of pts, especially adults, felt the COVID-19 pandemic had an impact on their medical care and emotional well-being. The impact of COVID-19 was also reflected in a decline in pt care, as reported by HCPs. In future, it would be interesting to understand the impact of the pandemic on vaccinated vs unvaccinated SCD pts.

Incidence of Post-Operative Complications and Factors Influencing Their Occurrence in Patients with Sickle Cell Disease in a Low-Income Country: A Case Study of Cameroon.

This study aimed to analyse post-operative complications and possible factors influencing their occurrence in the management of patients with sickle cell disease in a low-income country. We prospectively collected data regarding the management of patients with sickle cell disease requiring anesthesia for surgery in 11 Cameroonian hospitals from 1 May 2019 to 30 April 2021. The data were analysed using descriptive statistics and a binary logistic regression was used to determine the dependence between the variables. A total of 124 patients with sickle cell disease were enrolled; 64 were male and 60 female, giving a sex ratio of 0.93. The rate of post-operative complications was 23.4% (29/124) and the death rate was 3.2% (4/124). The female subjects had more complications than the male subjects p < 0.05. The number of vaso-occlusive crises experienced per year showed a significant impact on the occurrence of post-operative complications p < 0.05. Laparoscopic surgery had fewer post-operative complications 5/46 (10.9%) than laparotomy 14/43 (32.5%). The surgical technique for the abdominal procedures had a significant impact on the occurrence of post-operative complications p < 0.05. The type of surgery (p = 0.198) and the anaesthesia technique (p = 0.225) did not show a significant impact on the occurrence of post-operative complications. Particular attention should be paid to female patients with sickle cell disease as they are more likely to experience post-operative complications, as well as to the frequency of vaso-occlusive crises, which are also predictive of post-operative complications. Opting for laparoscopic surgery whenever possible would help to reduce post-operative complications.

Mechanisms underlying the adaptive pulp and jaw bone trabecular changes in sickle cell anemia.

Mechanisms underlying the oral outcomes in sickle cell anemia (HbSS) have been less explored. This study aimed to investigate the association of morbimortality indicators and hydroxyurea use with adaptive pulp and jaw bone trabecular changes in HbSS. This cross-sectional study included 123 individuals with HbSS. The exposures were the morbimortality indicators of HbSS (number of vaso-occlusive crises, organ damage, hemoglobin level, and leukocyte count) and the use of hydroxyurea for HbSS treatment. The outcomes were adaptive pulp and jaw bone trabecular changes confirmed by radiographic examination. Associations were estimated by Poisson regression in crude and adjusted analyses for sex, skin color, socioeconomic class, and age. The vaso-occlusive crises (mean ratio (MR)=3.5, p=0.045), lower hemoglobin (MR=2.4, p=0.037), and higher leukocyte count (MR=2.17, p=0.036) were risk factors, while the use of hydroxyurea was inversely associated with adaptive pulp changes (MR=0.23, p=0.024). The vaso-occlusive crises were associated with jaw bone trabecular changes (MR=1.33, p=0.02). Adaptive pulp changes may be a potential clinical marker of chronic vasculopathy in HbSS. The use of hydroxyurea may reduce the frequency of adaptive pulp changes.

Complete RH and Kell matching related to low alloimmunisation risk in sickle cell disease: prevalence and risk factors of alloimmunisation in a Spanish Tertiary Care National Reference Centre.

Red blood cell (RBC) transfusion remains an essential part of sickle cell disease (SCD) management but it can lead to alloimmunisation, with an increased incidence in this population. Prevention is based on RBC antigen phenotype matching, with complete RH and Kell matching being a standard of care. We performed a retrospective, single-centre study analysing alloimmunisation prevalence and risk factors in a cohort of transfused SCD patients. Eighty-seven patients (96.5% of paediatric age) received 1,781 RBC units (RBCu). Complete RH and Kell matched RBCu represented a median of 100% among total transfusions per patient. Of the 87 patients, 52 (59.8%) underwent chronic transfusion therapy, whereas 35 (40.2%) were only episodically transfused. Seven patients were alloimmunised (8.4%) and eleven antibodies were detected (alloimmunisation rate: 0.62/100 units transfused). 54.6% of these antibodies corresponded to RH-Kell despite the high accomplishment of the RH-Kell matching transfusion protocol. Alloimmunised patients had a median of 90.9% RH-Kell matched transfusions vs 100% in non-alloimmunised patients, but no statistical differences were observed (p=0.127). Number of transfused RBCu (19 vs 7; p=0.023), number of episodic RBCu (8 vs 2; p=0.006), episodic to chronic RBCu ratio (0.57 vs 0.09; p=0.045), number of vaso-occlusive crises (VOC) (4 vs 2; p=0.011), and autoantibody presence (57.1 vs 0%; p<0.001) were all statistically related to alloimmunisation. We report a low alloimmunisation prevalence (8.4%) related to a high grade of RH-Kell matching. However, deviation from 100% translates into alloimmunisation, with >50% of alloantibodies corresponding to RH-Kell. Alloimmunisation risk increases with transfusion burden, particularly during acute complications, and in patients with a higher number of VOC, probably reflecting underlying inflammation and disease severity. Further studies will be needed to elucidate additional risk factors and help prevent alloimmunisation in these patients.

Prevalence of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: A Retrospective US Claims Database Analysis

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting ~100,000 individuals in the US. SCD is considered a chronic, lifelong condition that requires comprehensive management. Vaso-occlusive crises (VOCs) are the most common complications of SCD, resulting in intense pain and potential irreversible organ damage. The objective of this study was to characterize the demographic and clinical characteristics of patients with SCD. Methods: A retrospective database analysis was conducted using data from the IBM MarketScan Commercial Claims and Medicare-Supplemental Claims database (July 1, 2013 to June 30, 2018). Patients were included if they met the following criteria: ≥2 diagnoses of SCD on different claims between July 1, 2013 and January 1, 2017, ≥6 years of age on January 1, 2017, and continuous enrollment throughout the 1-year study period (January 1, 2017 to December 31, 2017). Descriptive statistics were used to assess patient demographics (age and sex) and clinical characteristics (Charlson Comorbidity Index [CCI] and other selected comorbidities). In addition, the following outcomes were assessed: the proportion of patients who experienced ≥1 VOC, the frequency of VOCs by care setting, the duration of inpatient VOCs, the monthly VOC risk, and the time between subsequent VOCs. Results: A total of 8174 patients met the inclusion criteria. The mean (± standard deviation [SD]) age was 40.8 (±19.5) years and 63.5% of the patients were female. The mean (±SD) CCI was 0.6 (±1.3), with chronic pulmonary disease, diabetes, renal disease, cerebrovascular disease, and stroke identified as the most common comorbidities. Approximately 20% (n=1659) of patients experienced ≥1 VOC and the mean monthly VOC risk was 0.07 (±0.19). Among patients with ≥1 VOC, the mean (±SD) number of VOCs was 5.2 (±7.7) and the median (interquartile range) time from first to second VOC was 2.4 (0.5-8.2) months. Approximately 18% (n=1461) of patients experienced ≥1 VOC managed in an outpatient setting and 10% (n=844) of patients experienced ≥1 VOC managed in an inpatient setting. Approximately 8% (n=646) of patients experienced ≥1 inpatient and ≥1 outpatient VOC during the study period. Among patients with ≥1 outpatient VOC, the mean (±SD) number of outpatient VOCs was 4.6 (±6.9); among patients with ≥1 inpatient VOC, the mean (±SD) number of inpatient VOCs was 2.2 (±2.3) and the mean (±SD) inpatient VOC duration was 6.6 (±6.4) days. Conclusions: VOCs are common complications of SCD, affecting a subset of patients who often experience recurrent VOC episodes requiring professional health care. VOCs are associated with a significant disease burden on the patient and, potentially, the health care system. Disclosures Oladapo: Takeda:Current Employment, Current equity holder in publicly-traded company.Swallow:Analysis Group, Inc.:Current Employment.Briggs:Analysis Group, Inc.:Current Employment.Zichlin:BMS:Other: Employee of Analysis Group Inc., which received consulting fees.Mellgard:Baxalta US Inc., a Takeda company:Current Employment, Current equity holder in publicly-traded company.

An Adaptive, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)

An Adaptive, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)

An Age Analysis of the International Sickle Cell World Assessment Survey (SWAY), Focusing on Symptoms, Treatment Goals and the Impact of SCD on Patients' Daily Lives

An Age Analysis of the International Sickle Cell World Assessment Survey (SWAY), Focusing on Symptoms, Treatment Goals and the Impact of SCD on Patients' Daily Lives

Vaso-occlusive crises and costs of sickle cell disease in patients with commercial, Medicaid, and Medicare insurance – the perspective of private and public payers

Aim To characterize vaso-occlusive crises (VOCs) and describe healthcare costs among commercially-insured, Medicaid-insured, and Medicare-insured patients with sickle cell disease (SCD). Materials and methods The IBM Truven Health MarketScan Commercial (2000–2018), Medicaid Analytic eXtract (2008–2014), and Medicare Research Identifiable Files (2012–2016) databases were used to identify patients with ≥2 SCD diagnoses. Study measures were evaluated during a 12-month follow-up period, stratified by annual number of VOCs (i.e. 0, 1, and ≥2). Results Among 16,092 commercially-insured patients (mean age = 36.7 years), 35.3% had 1+ VOCs. Mean annual total all-cause healthcare costs were $15,747, $27,194, and $64,555 for patients with 0, 1, and 2+ VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 31.0%, 1 VOC = 53.1%, 2+ VOCs = 65.4%) and SCD-related costs (0 VOC = 56.4%, 1 VOC = 78.4%, 2+ VOCs = 93.9%). Among 18,287 Medicaid-insured patients (mean age = 28.5 years, fee-for-service = 50.2%), 63.9% had 1+ VOCs. Mean annual total all-cause healthcare costs were $16,750, $29,880, and $64,566 for patients with 0, 1, and 2+ VOCs, respectively. Inpatient costs (0 VOC = 37.2%, 1 VOC = 64.3%, 2+ VOCs = 72.9%) and SCD-related costs (0 VOC = 60.9%, 1 VOC = 73.8%, 2+ VOCs = 92.2%) accounted for a significant proportion of total all-cause healthcare costs. Among 15,431 Medicare-insured patients (mean age = 48.2 years), 55.1% had 1+ VOCs. Mean annual total all-cause healthcare costs were $21,877, $29,250, and $58,308 for patients with 0, 1, and ≥2 VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 47.9%, 1 VOC = 54.9%, 2+ VOCs = 67.5%) and SCD-related costs (0 VOC = 74.9%, 1 VOC = 84.4%, 2+ VOCs = 95.3%). Limitations VOCs managed at home were not captured. Analyses were descriptive in an observational setting; thus, no causal relationships can be inferred. Conclusions A high proportion of patients experienced VOCs across payers. Furthermore, inpatient and SCD-related costs accounted for a significant proportion of total all-cause healthcare costs, which increased with VOC frequency.

Ticagrelor versus placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: Rationale and design of a randomized, double-blind, parallel-group, multicenter phase 3 study (HESTIA3)

BackgroundAn unmet need for therapies exists to reduce sickle cell disease (SCD) complications in pediatric patients. Activated platelets contribute to the formation of cellular aggregates during sickling and vaso-occlusive crises (VOCs). Ticagrelor is an oral, direct-acting, and reversible adenosine diphosphate P2Y12 receptor antagonist that inhibits platelet activation and aggregation. Although ticagrelor was well tolerated in two phase 2 studies in children and young adults with SCD, larger and longer-term treatment studies are needed to assess ticagrelor's efficacy to reduce VOCs. HESTIA3 will evaluate the efficacy, safety, and tolerability of ticagrelor versus placebo over a minimum of 1 year (maximum 2 years) in pediatric patients with SCD. MethodsApproximately 180 patients (aged ≥ 2 to <18 years) with SCD (≥ 2 VOCs in the prior year) from 18 countries will be randomized 1:1 to ticagrelor or placebo. Primary endpoint: number of VOCs (a composite endpoint of painful crises and/or acute chest syndrome); key secondary endpoints: hospitalizations, pain intensity and analgesic use during VOCs, acceptability of formulation, and health-related quality of life. The weight-based doses of ticagrelor are set by modeling and simulation. Platelet inhibition data, measured by the vasodilator-stimulated phosphoprotein assay, will be collected for exploratory purposes. ConclusionsHESTIA3 aims to demonstrate that using greater target platelet inhibition than previous studies on SCD, ticagrelor will decrease the frequency of VOC in pediatric patients.Trial Identifier: NCT03615924; EudraCT2017-002421-38.

Sustainability of Hematological and Clinical Benefits to HU Administration in the Prevention of Sickle-Cell Vaso-Occlusive Crises in Routine Practice

Hydroxyurea (HU) is approved in EU and USA for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle-cell disease (SCD).Further to the double blinded, randomized controlled Multicenter Study of Hydroxyurea administration (MSH) which provided the first data on clinical efficacy of HU (Charache 1995), a few follow-up studies suggested that long-term use of HU resulted in significant clinical benefit on patient outcome. This was reflected by lower mortality rates in HU-treated patients compared to conventionally treated patients (Steinberg 2003 & 2010, Voskaridou 2010, Lê 2015). Sustained hematological and clinical response after several years of follow-up at maximal tolerated dose was further shown in subsequent studies, especially the LaSHS study (Voskaridou 2010).Based on these data, the ESCORT-HU (European Sickle Cell Disease COhoRT - HydroxyUrea) study was launched aiming in the establishment of the safety and the sustainability of hematological and clinical benefits to HU administration in the prevention of sickle-cell vaso-occlusive crises in routine practice. We hereby present preliminary results from a large cohort of patients enrolled in the study between January 2009 and June 2017.1920 patients were enrolled from 63 centers in France, Germany, Greece and Italy, For 147 of the 600 HU-naive patients (never treated with HU before enrolment) and started on HU for VOC or ACS, there was documented clinical outcome (number of VOC >48h and ACS episodes per year) over a 4-year follow-up period. These patients were selected for analysis to evaluate sustainability of clinical and hematological HU response in routine practice.Demographic data and Hb genotypes are displayed in table 1. The children group was mainly composed of βS/βS patients, while adults were mainly βS/βS and βS/β-thal patients. As shown in figure 1 and 2, there was a dramatic reduction in the number of VOC >48h and ACS episodes (-79%) from year 1 in adults and children, with results comparable to previous randomised clinical trials in adults (Charache et al., 1995) and children (Jain et al, 2012). Overall, the reduction in number of VOC (>48h) and ACS was stable over the 4 years of follow-up. This reduction is inversely proportional to the increase in HbF. There were however a moderate rebound in children from year 2 while adults remained stable. Similarly, there was reduction in the proportion of adults and children requiring transfusion (figure 3). The clinical benefit of HU was higher in severe forms of SCD, as displayed by the markedly reduced number of patients with ≥ 3 VOC episodes (>48h)/year at year 1 (figure 4).Hematological response to HU was evidenced as soon as year 1 with a marked increase in HbF% (+6-10) and were maintained over subsequent years of treatment (figure 1 and 2) as the dose of HU was further increased. While there was no striking differences in HbF% variation between age groups and genotypes, the requirement for increase in HU dose over the 4 years of follow-up was markedly higher in children, probably reflecting the different severity between the two population at entry (figure 5). The red cell red cell mean corpuscular volume (MCV) could be used as a measurement of compliance, showing differences between age group (figure 5).There was, as expected, an apparent negative correlation between induction of HbF synthesis and number of VOC >48h and ACS episodes at year 1, attesting to reduced effectiveness of treatment in some patients (figure 6).Improvement in blood parameters was accompanied by mild reduction of absolute neutrophil and platelet count although not to the point of myelosuppression (defined as ANC < 2 x 109/L), showing that MTD was not targeted in routine practice.Treatment-emergent adverse reactions occurring in the 147 patients of the cohort over the 4 years of follow-up were consistent with the known safety profile of hydroxyurea. The commonest effects included neutropenia and thrombocytopenia (25 events in 13 patients) and were easily manageable with temporary discontinuation of treatment. No tumorigenesis was reported.In conclusion, preliminary results from ESCORT-HU in 147 patients treated with HU showed sustained hematological and clinical response while MTD was not targeted, with differences between adults and children which may be attributed in part to reduced compliance in the latter group. DisclosuresVoskaridou:Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acceleron: Membership on an entity's Board of Directors or advisory committees, Research Funding. Oevermann:Addmedica: Membership on an entity's Board of Directors or advisory committees. Thuret:Addmedica: Research Funding; bluebird bio: Research Funding; Novartis: Research Funding. Steschenko:Novartis: Membership on an entity's Board of Directors or advisory committees.

Clinical and Laboratory Effects of Hydroxyurea in Children and Adolescents with Sickle Cell Anemia: A Portuguese Hospital Study

Our aim was to assess the efficacy and safety of hydroxyurea (HU) in children with severe forms of sickle cell anemia followed in a Portuguese hospital. We carried out an open-label, uncontrolled prospective study, which included children with severe forms of sickle cell anemia. Hydroxyurea was started at 15 mg/kg/day and increased to a maximum dose of 25 mg/kg/day. Patients were monitored to assess compliance, clinical and hematological response and toxicity. Nine children and adolescents, five girls and four boys, with a median age of 13 years (range 8 to 16) were enrolled in the study during a period of 24 months. All patients completed at least 15 months of therapy. Hb F was significantly increased, from a mean of 7.0 ± 3.9% to 13.7 ± 5.3% (p = 0.028). Clinically, all patients responded significantly with a reduction of 80% in the number of vaso-occlusive crises (VOC), 69% in hospital admissions, 76% in hospitalization days and 67% in transfusion requirements, without significant toxicity. We concluded that, in our population, HU proved to be effective in increasing Hb F levels, and in decreasing hospitalizations for VOC and transfusion requirements with no major side effects. Long-term clinical follow-up is important to certify benefit maintenance.

Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia

PURPOSE: This open-label pilot study was designed (1) to determine the effect of hydroxyurea on the hemoglobin level in children with sickle cell anemia, (2) to evaluate the toxicity of hydroxyurea, and (3) to assess any impact of hydroxyurea on the frequency of vaso-occlusive crises (VOCs). PATIENTS AND METHODS: Ten children (group 1) with three or more VOCs of the extremities or two or more VOCs of the lungs (acute chest syndrome) in the preceding 12 months, and five children (group 2) with hemoglobin levels less than 70 gm/L were treated with hydroxyurea in doses of 20 to 35 mg/kg per day. The frequency of VOCs before hydroxyurea therapy was compared with the frequency during therapy, and the peak hemoglobin levels during hydroxyurea therapy were compared with the pretreatment values. RESULTS: One patient in group 1 was removed from the study within 1 month because of nausea. Seven of the remaining nine patients in group 1 had a decrease in the frequency of VOCs. The number of VOCs per patient-year for all 14 patients decreased from 2.5 before hydroxyurea therapy to 0.87 during hydroxyurea therapy, a decrease of 65% ( p <0.00001). Two of five patients in group 2 had an increase in hemoglobin of 27 gm/L and 34 gm/L over the baseline. The median rise in hemoglobin was 19 gm/L (range, 7 to 37) for all 14 patients. Nine patients are still receiving hydroxyurea for a median period of 23 months (range, 18 to 59). CONCLUSIONS: Hydroxyurea decreases the severity of anemia in some patients, and it may decrease the frequency of VOC. Its short-term hematologic toxicity is minimal. (J P EDIATR 1996;129:559-65)