Hydroxyurea Is Associated with Early Onset Malaria Episode in Treated Sickle Cell Disease Patients

Abstract Hydroxyurea (HU) is the only drug which has demonstrated efficacy in terms of reduced incidence of VOC and ACS, reduced need for hospitalization and reduced number of blood transfusion in sickle cell disease. African countries are among those with highest rate of both malaria and sickle cell disease. Despite of that the heterozygous form (HbAS) is known to protect against malaria, there is no documented studies on the clinical effect of HU on malaria. 36 patients aged 4 to 60 years old and treated by HU at the sickle cell disease research and control center of Bamako for at least 2 years. The treated group was compared to a matched untreated sickle cell patients group. During the follow-up, malaria incidence and onset to clinical episode of malaria were compared between treated SCD patients and untreated group. Results of the comparison show that there is no increased incidence of malaria in the treated group after 2 years follow-up (P=0.9). However, a reduction on the time to first malaria episode within the sickle cell population treated with HU was observed (P=0002).Based on this observed reduced time to first malaria episode in HU treated SCD patients, the use of HU in malaria endemic areas needs to be revaluated. It is howether clear that a more comprehensive approach would hopefully reduce the morbidity due to HU use for SCD affected children. Disclosures No relevant conflicts of interest to declare.

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Enalapril Therapy Prevents Cardiac Remodelling of Sickle Cell Disease Patients.

Blood ◽

10.1182/blood.v108.11.3792.3792 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3792-3792

Author(s):

Sara T. Saad ◽

Carmen S. Passos Lima ◽

Osvaldo M. Ueti ◽

Adriana A. Ueti ◽

Kleber G. Franchini ◽

...

Keyword(s):

Blood Pressure ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Ace Inhibitors ◽

Aortic Root ◽

Fetal Hemoglobin ◽

Treated Group ◽

Left Ventricular ◽

Cell Disease

Abstract Angiotensin-converting enzyme (ACE) inhibitors are capable of decreasing cardiac remodelling in patients with cardiac dysfunction, however their effects on sickle cell disease (SCD) are unknown. Thus, this study aimed to investigate the cardiac effects of enalapril on SCD patients. Thirteen adult patients with sickle cell disease (SCD) and microalbuminuria (3M/10F); 11 sickle cell anemia patients (SCA), 1 Sβ thalassemia patient (Sβ) and 1 patient with hemoglobin SC (SC) were treated with enalapril. Thirteen other SCD patients (4M/9F) without microalbuminuria, matched according to age, diagnosis (11 SCA, 1 Sβ and 1 SC), and levels of hemoglobin, hematocrit and fetal hemoglobin, did not receive enalapril and were followed up as the control group in the same period of study. In the treated group, enalapril (5mg) was administered to 9 SCD patients during the entire study period. One patient did not complete follow-up, and higher doses (7.5mg to 20mg) were administered to 3 patients who developed systolic BP over 120 mmHg during the study period. Median age (28.5 vs 29.0; P= 0.580), baseline values of hemoglobin (8.5 vs 8.4g/dL, P= 0.600), hematocrit (25.0 vs 23.5%, P= 0.500), fetal hemoglobin (4.4 vs 4.1%, P=0.720) and mean blood pressure (MBP; 80 vs 93mmHg, P= 0.13) were similar in treated and untreated patients Echocardiograms were performed before the study entry and once a year in patients and controls. Comparisons of groups were performed at the beginning of the study and after 36 months of follow-up using the Wilcoxon-signed rank test and Spearman coefficient. At 36 months of follow-up, MBP was lower than the baseline value (93 mmHg vs 87 mmHg, P= 0.018) in the treated group. Significant increases in left ventricular mass (192 vs 231g, P= 0.005), posterior left ventricular wall thickness in end-diastole (8.5 vs 10.0mm, P= 0.013), left ventricular mass index (114.4 vs 131g/m2, P= 0.043), interventricular septal wall thickness in end-diastole (9.0 vs 9.5mm, P= 0.036) and aortic root dimension (28 vs 32mm, P= 0.009) values were seen in untreated, but not in enalapril treated patients. No major changes were seen in left ventricular ejection fraction, left ventricular systolic diameter, left ventricular diastolic dimension and left atrial diameter, in both groups, along the observational period. No significant correlation was detected between the data here presented. At the end of the study, no symptoms or signals related to cardiac failure were found in any of the enrolled patients. These results indicate a trend toward cardiac and aortic root remodeling in untreated SCD patients and suggest that long-term treatment with ACE inhibitors has beneficial effects on the cardiac remodeling of SCD patients and could be indicated for adult patients, if an increase in baseline blood pressure occurs.

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Intermittent Use Of Sufadoxine-Pyrimethamine To Prevent Malaria In Patients With SCD In Malaria Endemic Regions: Findings From The Sickle Cell Disease Research and Control Center Of Bamako, Mali

Blood ◽

10.1182/blood.v122.21.1006.1006 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1006-1006

Author(s):

Dapa Aly Diallo ◽

Aldiouma Guindo ◽

Boubacari Ali Touré ◽

Yaya Sarro ◽

Baba Fané ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Sub Saharan Africa ◽

Health District ◽

Cell Disease ◽

Serious Adverse Events ◽

Control Center ◽

Disease Research ◽

And Control

Abstract Sickle cell disease (SCD) is a chronic disorder affecting erythrocytes and is especially prevalent throughout Sub-Saharan Africa where malaria is thought to be a significant cause of morbidity and mortality in affected individuals. In the absence of effective malaria vaccine, one of the affordable alternatives to prevent malaria at present is chemoprophylaxis. In order to evaluate the effectiveness of a monthly intermittent prophylaxis treatment (IPT) with sulfadoxine-pyrimethamine (SP) during high malaria transmission season in patients with sickle cell disease, two groups of SCD patients from two different sites were compared. The first group constituted of patients followed at the Sickle Cell Disease Research and Control Center of Bamako where IPT is routinely administered while the second group consisted of individuals enrolled in the health district in the same locality but no malaria prophylaxis. In this area, the incidence of resistance of P.falciparum to SP is estimated < 10%. SP combination was administrated as follows: sulfadoxine 25mg/kg and pyrimethamine 1.25mg/kg. For both groups, diagnosis of malaria was performed by using the rapid diagnosis test for the presence of P.falciparum. From 2011 to 2012, 687 SCD patients (457 from the Sickle Cell Disease Research and Control Center and 115 from the health district) were enrolled. The observed prevalence of malaria infection in the group receiving a monthly IPT by SP (1.5%) was much lower than the group (6%) for which IPT was not offered (P=0.01). When data was stratified by hemoglobin genotypes, malaria was found to occur entirely in SS and SC patients and no malaria cases were observed in S/β-thalassemia patients. SP was well tolerated since no patient in SP arm reported pruritus and no serious adverse events including death were recorded during the study. In malaria endemic areas where the incidence of resistance to SP is low, anti-malarial prophylaxis with this combination therapy significantly reduced the incidence of malaria in SCD patients with good safety and a lower cost. Disclosures: No relevant conflicts of interest to declare.

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The Cerebral Vasculopathy In Malian Sickle Cell Anemia Children: Lesson From Routine Transcranial Doppler Screening

Blood ◽

10.1182/blood.v122.21.4687.4687 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4687-4687

Author(s):

Dapa Aly Diallo ◽

Aldiouma Guindo ◽

Alain Dorie ◽

Boubacari Ali Touré ◽

Baba Fané ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Transcranial Doppler ◽

Conflicts Of Interest ◽

Fetal Hemoglobin ◽

Preventive Treatment ◽

Cell Disease ◽

Control Center ◽

Increased Risk ◽

Patients At Risk

Cerebral vasculopathy is one of the major complications of Sickle Cell Disease (SCD). 11% of the homozygous SCD patients experience stroke by age of 20 years. The use of Transcranial Doppler (TCD) allows identification of patients at risk for stroke and leads to implementation of a preventive treatment that contributes to limit the burden of SCD particularly during childhood. Using TCD screening, we evaluated the prevalence and incidence of cerebral vasculopathy in Malian SCD children. During the years 2008 to 2013, 572 children, 249 girls and 323 boys, age range (2-17yrs) were routinely screened by TCD at our Sickle Cell Disease Research and Control Center of Bamako, Mali. The overall prevalence of cerebral vasculpathy defined by conditional (1.5-1.79 cm/sec) and abnormal TCD (≥ 1.80 cm/sec) in this population is 17.1%. The highest proportion (92.9%) was observed in homozygous SCD patients while the percentage of affected patients was much lower in S/β0thalassemia (4.1%) and in SC (3.1%) patients. No cases were observed in S/β+thalassemia patients. SCD children <9 years old were more susceptible to cerebral vasculopathy complications than those above this age threshold (P<0.001). Low hemoglobin levels and low fetal hemoglobin were associated with an increased risk of cerebral vasculopathy. During the study, 4 of 444 children with normal TCD converted to conditional TCD, while 5 of 68 children with conditional TCD converted to abnormal TCD. This conversion from conditional to abnormal TCD was associated with a mean decrease in Hb value of 0.37g/dL (P=0.002). In conclusion this study shows high prevalence and incidence of cerebral vasculopathy in Malian SCD children. While chronic transfusion programs significantly reduces the risk of stroke in SCD patients with abnormal TCD, at present there are no well articulated strategies to prevent conversion from conditional to abnormal TCD. A more comprehensive approach would hopefully reduce the morbidity and mortality due to cerebral vasculopathy in SCD affected children. Disclosures: No relevant conflicts of interest to declare.

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Hydroxyurea to Treat Pediatric Sickle Cell Disease in Haiti - a Preliminary Report

Blood ◽

10.1182/blood.v128.22.1313.1313 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1313-1313

Author(s):

Nicholas McGregor ◽

Emmeline Lerebours ◽

Prasad Bodas

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Laboratory Data ◽

The United States ◽

Western Hemisphere ◽

Cell Disease ◽

Open Label ◽

Serious Adverse Events

Abstract Introduction. Haiti is the poorest nation in the Western Hemisphere, and the prevalence of sickle cell disease (SCD) in thatnation is twice that among African-Americans in the United States. Patients with SCD in Haiti have limited access to preventative care and disease management measures due to scarce healthcare resources. Hydroxyurea (HU) is a compelling option for the amelioration of complications of SCD in Haiti due to its relatively low cost, proven safety, and well-documented efficacy. Hydroxyurea programs have been implemented in India and in several African settings, however little data existto demonstrate the acceptability or feasibility of such an effort in Haiti. Study Design/Objectives. This is an open label, single arm pilot study with the primary objective of examining the acceptability and feasibility of the use of HU to treat children with SCD in an existing pediatric SCD program in Port-au-Prince, Haiti. Acceptability was defined as enrollment of a minimum of two-thirds of patients who are offered participation in the study. Feasibility was defined as two thirds of the enrolled patients being compliant with a defined minimum number of mandated study visits, lab draws, and HU doses. Secondary objectives include documenting the effect of HU on renal, hepatic, and bone marrow function as well as describing the incidence of clinical events in Haitian sickle cell patients taking HU. Methods. Patients with HbSS disease, age 2-15 years, who met minimum hematologic, renal, and hepatic parameters, were eligible for the study. Patients were approached for inclusion into the study consecutively during three separate enrollment periods from November 2015 through June 2016. The starting dose of Hydroxyurea (capsule and suspension form were available) was 20mg/kg which was increased to a maximum dose of 25mg/kg. Study visits occurred every 4 to 8 weeks at which point laboratory and clinical efficacy parameters, as well as potential adverse effects history were collected and dose modifications occurred. The study period for each patient will last 1 year. Akron Children's Hospital (ACH) IRB and the Haitian National Ethics Board approved the study. Funding for this project is provided through grants from the American Academy of Pediatrics and the ACH Foundation. Results. The study is ongoing with the enrollment period being closed as of June 2016. Forty-three patients have been enrolled, with a mean length of participation of 17.6 weeks (range 0-32 weeks).Forty-seven patients were offered participation in the study and 45 signed consent and underwent the screening process, generating an acceptability measure of 95.7%. Two out of the 45 screened patients were excluded based on results from screening labs (1 non-HbSS on confirmatory electrophoresis, 1 severe anemia) resulting in the final enrollment of 43 patients (23M:20F, mean age 9 years). Feasibility is being actively assessed.There have been no serious adverse events and no deaths. Three out of 43 enrolled patients were lost to follow-up and removed from the study due to missing 3 consecutive study visits (see figure 1). Compliance with mandated study visits was high among the enrolled patients with an attendance of 92.9% of the visits. Percent attainment of mandated laboratory tests is shown in table 1. No patients have had HU dose interruptions based on abnormal lab tests. Sixteen study patients have 6 month hematologic laboratory data available at this time: mean Hemoglobin and MCV have increased from 7.1 to 7.9g/dL and 90.6 to 107.1fL, respectively, and mean WBC and platelet count have decreased from 18.0 to 12.4(10^9/mL) and 557 to 413(10^9/mL), respectively. Conclusion. Results suggest that HU isan acceptable option for treating children with sickle cell disease in Haiti. Our preliminary data show that HU is feasible, safe, and effective in this setting. Challenges exist in ensuring reliable laboratory follow-up and will likely have to be addressed on an individual clinic and laboratory basis. Disclosures No relevant conflicts of interest to declare.

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Health Status of Offspring Conceived During Hydroxyurea Therapy for Sickle Cell Disease.

Blood ◽

10.1182/blood.v114.22.1533.1533 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1533-1533

Author(s):

Saloni Tanna ◽

Betsy Clair ◽

Sejal Kuthiala ◽

Teresa A. Coleman ◽

Abdullah Kutlar

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Attention Deficit Disorder ◽

Life Support ◽

Conflicts Of Interest ◽

Case Reports ◽

National Registry ◽

Cell Disease ◽

Apgar Scores

Abstract Abstract 1533 Poster Board I-556 Hydroxyurea (HU) is an S-phase specific cytotoxic agent (pregnancy category D), approved for use in sickle cell disease (SCD) primarily due to its ability to augment production of fetal hemoglobin (HbF), which has been shown to reduce the frequency of pain crises and decrease the need for blood transfusions. In all animal species tested, HU produced an increase in congenital anomalies. Defects of the central nervous system, palate, and skeleton occurred in rats treated with HU in the ninth to twelfth gestational days. Embyonic cytotoxicity may be secondary to formation of reactive free radicals. Because of its teratogenic potential, patients with SCD are instructed to practice contraception while on HU therapy. However, risks associated with maternal or paternal HU exposure at the time of conception is unclear. Our review of the literature has only shown six case reports of HU exposure in pregnancy for the treatment of SCD. Two of these pregnancies were terminated with medical abortion, the remaining four cases described liveborn infants with normal phenotypes at 15 to 21 months of follow up. 236 patients followed at the Medical College of Georgia Sickle Cell Center have been on HU for a period of 6 months to 14 years. Despite precautionary counseling, we have identified seven women and three men with SCD who have conceived while on HU therapy. We analyzed the birth records of ten children conceived during HU therapy. The duration of HU therapy varied from 2 weeks to 3 years at the time pregnancy was diagnosed; gestational age when HU was discontinued ranged from 3 to 10.5 weeks. Some children were born prematurely or preterm, with birth weights ranging from 922 to 3178 grams. APGAR scores ranged from 2 to 9 for the first minute and 8 to 10 for the five minute score. One child who had been born severely premature at 26 weeks with a birth weight of 922 grams and APGAR scores of 2 and 8 at one and five minutes to a father who had been on HU at the time of conception was ultimately withdrawn from life support measures. The remaining nine children were assessed for appropriate development by questionnaires provided to parents as well as pediatric records when available. One child with APGAR scores of 5 and 9 has been diagnosed with mental retardation and attention deficit disorder. Developmentally, the other eight children have achieved appropriate milestones. Women with sickle cell disease are more likely to develop complications such as intrauterine growth retardation and preterm delivery than those without the disease. These findings suggest that children conceived on HU therapy are not significantly different from other infants born to parents with SCD who are not on HU. Our sample size is not large enough to observe the potential effects of in utero HU exposure. The small number of subjects is likely secondary to potential teratogenicity discouraging women to become pregnant as well as paucity of exposed pregnancies due to menstrual disturbances induced by HU. It is therefore important to develop and maintain a national registry to allow longer follow up of exposed children and more careful assessment of fetotoxic effects for those conceived during HU therapy for SCD. Disclosures No relevant conflicts of interest to declare.

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Improvement of Sickle Cell Disease Morbimortality in Children: Experience in a Remote Area of an African Country

10.21203/rs.3.rs-92545/v1 ◽

2020 ◽

Author(s):

Benoît Mukinayi MBIYA ◽

Didier Kalenda Kalombo ◽

Yannick Nkesu Mukendi ◽

John Kalenda Mpoyi ◽

Parola Mukendi Biboyi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Rural Areas ◽

African Country ◽

Public Health Problem ◽

Annual Number ◽

Cell Disease ◽

African Countries ◽

Referral Center

Abstract Background: Sickle cell disease (SCD) is a public health problem in the Democratic Republic of Congo. While reference sickle cell centers have been implemented in capital cities of African countries and have proven to be beneficial for SCD patients, they have never been set up in rural areas for families with very low sources of income. Method: A cohort of 143 children with SCD aged 10 years old (IQR (interquartile range): 6–15 years) (sex ratio male/female = 1.3) were clinically followed for 12 months without any specific intervention aside from the management of acute events, and then for 12 months with a monthly medical visit, biological follow-up, and regular prophylaxis. Results: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1–5). The implementation of standardized and regular follow-ups in a new sickle cell referral center in a remote city showed an increase in the annual mean hemoglobin level from 50 to 70 g/L (p = 0.001), and a decrease in the lymphocyte count and spleen size (p < 0.001). A significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes of vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes were also observed. Conclusions: Creation of a sickle cell referral center and the regular follow-up of children with SCD are possible and applicable in the context of a remote city of an African country and represent simple and accessible measures that can reduce the morbimortality of children with sickle cell disease.

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Improvement of Sickle Cell Disease Morbi-Mortality in Children: Experience Gained in a Remote Area of an African Country

10.20944/preprints202005.0305.v2 ◽

2020 ◽

Author(s):

Benoît Mukinayi Mbiya ◽

Didier Kalenda Kalombo ◽

Yannick Nkesu Mukendi ◽

Valery Daubie ◽

John Kalenda Mpoyi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

African Country ◽

Public Health Problem ◽

Annual Number ◽

Cell Disease ◽

Medical Visit ◽

African Countries ◽

Referral Center

Background: Sickle cell disease (SCD) is a public health problem in the Democratic Republic of Congo. If reference sickle cell centers have been implemented in capital-cities of African countries and have proven to be beneficial for SCD patients, it has never been set up ina rural area for families with very low sources of income. Method: A cohort of 143 children with SCD aged 10 years old (IQR [inter quartile range]: 6–15 years) (sex ratio male: female = 1.3) were clinically followed for 12 months without any specific intervention, outside management of acute events ,and then 12 months with a monthly medical visit , a biological follow-up and regular prophylaxis. Results: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1–5). The implementation of standardized and regular follow-up in a new sickle cell referral center in a remote city showed an increase in the annual mean hemoglobin level from 50 to 70 g/L (p = 0.001), and a decrease of the lymphocytes count and spleen size (p < 0.001). A significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes of vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes were also observed. Conclusions: Creation of a sickle cell referral center and a regular follow-up of children with SCD are possible and applicable in the context of a remote city of an African country. Those simple and accessible measures can reduce the morbimortality of the sickle cell children.

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Improvement of Sickle Cell Disease Morbimortality in Children: Experience in a Remote Area of an African Country

10.20944/preprints202005.0305.v3 ◽

2020 ◽

Author(s):

Benoît Mukinayi Mbiya ◽

Didier Kalenda Kalombo ◽

Yannick Nkesu Mukendi ◽

Valery Daubie ◽

John Kalenda Mpoyi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Rural Areas ◽

African Country ◽

Public Health Problem ◽

Annual Number ◽

Cell Disease ◽

African Countries ◽

Referral Center

Background: Sickle cell disease (SCD) is a public health problem in the Democratic Republic of Congo. While reference sickle cell centers have been implemented in capital cities of African countries and have proven to be beneficial for SCD patients, they have never been set up in rural areas for families with very low sources of income. Method: A cohort of 143 children with SCD aged 10 years old (IQR (interquartile range): 6–15 years) (sex ratio male/female = 1.3) were clinically followed for 12 months without any specific intervention aside from the management of acute events, and then for 12 months with a monthly medical visit, biological follow-up, and regular prophylaxis. Results: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1–5). The implementation of standardized and regular follow-ups in a new sickle cell referral center in a remote city showed an increase in the annual mean hemoglobin level from 50 to 70 g/L (p = 0.001), and a decrease in the lymphocyte count and spleen size (p < 0.001). A significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes of vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes were also observed. Conclusions: Creation of a sickle cell referral center and the regular follow-up of children with SCD are possible and applicable in the context of a remote city of an African country and represent simple and accessible measures that can reduce the morbimortality of children with sickle cell disease.

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Sickle-Cell Disease and Malaria: Evaluation of Seasonal Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine in Senegalese patients—a Randomized Placebo-Controlled Trial

Blood ◽

10.1182/blood.v116.21.1633.1633 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1633-1633 ◽

Cited By ~ 1

Author(s):

Saliou Diop ◽

Moussa Seck ◽

Youssou Bamar Gueye ◽

Fabienne Soudre ◽

Awa Oumar Touré Fall ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Malaria Incidence ◽

Controlled Trial ◽

Intermittent Preventive Treatment ◽

Public Health Problem ◽

Preventive Treatment ◽

Cell Disease ◽

The Impact

Abstract Abstract 1633 Malaria is a real public health problem in Africa, more than 300 million new cases and approximately two million deaths arise every year. Sickle-cell disease (SCD) patients are at high risk of developing malaria which is a major contributor to morbidity and mortality in this disease. In Senegal, malaria transmission is high during rainy season, between July and October, and it was noted that sickle-cell crisis are frequent during this period. Then we carried out a double-blind randomized controlled trial to compare the impact of monthly sulfadoxine-pyrimethamine (SP) during the high-transmission season versus placebo on malaria incidence and morbidity of sickle-cell anemia. Sixty (60) SCD patients were randomized either to receive three intermittent preventive treatment (ITP) with SP or placebo using the random permutation table with nine elements. The drug was administrated as follows: sulfadoxine 25 mg/kg and pyrimethamine 1.25 mg/kg and this treatment was given once during the following months: September, October, and November. Overall four episodes of malaria disease were diagnosed, all these cases in the placebo arm. Thus, overall prevalence was 6.6% and there was no other case of malaria in the SP arm during the study period. Parasitological diagnosis confirmed the presence of Plasmodium falciparum in all four cases. No patient death was encountered during the study. SP treatment was well tolerated as only one patient (1.6%) in the SP arm reported pruritis. A significant reduction of patients’ complaints (p= 0.002) and blood requirements (p = 0.001) was noted in the SP group; whereas, no impact was observed on vaso-occlusive crisis and hospitalization occurrence. Malaria prophylaxis by monthly intake of SP during the transmission period of the parasite reduced the prevalence of malaria and was safe in SCD patients leaving in malaria endemic area. Disclosures: No relevant conflicts of interest to declare.

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Optimizing Hydroxyurea Use in Children with Sickle Cell Disease: Least Tolerated Dose Is Effective

Blood ◽

10.1182/blood.v118.21.4851.4851 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4851-4851

Author(s):

Sharef Waadallah Sharef ◽

Maya Al-Hajri ◽

Ismail Beshlawi ◽

Amer Qais Al-Shahrabally ◽

Yasser Wali

Keyword(s):

Abdominal Pain ◽

Side Effects ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Annual Number ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Starting Dose

Abstract Abstract 4851 Background: Hydroxyurea (HU) is an antimetabolite that effectively ameliorates the course of sickle cell disease (SCD). Starting dose is usually 20 mg/kg/day and the dose is escalated up to 35 mg/kg/day in most of the centers. In Oman, due to high level of consanguinity, ethnic neutropenia affects around 10% of population rendering higher doses difficult to maintain in most of the patients. Materials and Methods: 161 patients (age 2–16 years, 61% male and 39% female) with SCD at Sultan Qaboos University Hospital, Muscat, Oman, were started on HU for clinically severe course (defined as: annual vaso occlusive crisis admissions more than 3, and/or occurrence of acute chest syndrome) with starting dose of 15 mg/kg and a mean dose of 18 mg/kg/day. All patients were included in the study except for 19 patients who were excluded for various reasons (8 lost follow up, 6 stopped HU by parents, and 5 stopped due to side effects: dizziness, abdominal pain, and myelosuppression). Remaining 142 patients were followed up for median treatment duration of 4 years (range, 1.5–10 years). Patients were assessed for clinical and laboratory response to HU. Results: There was significant reduction in the annual number of admissions due to vaso occlusive crisis (P <0.001, Wilcoxon Signed Ranks Test) with a mean of 4.7 and 1.5 before and after HU use respectively. There was also observed clinical improvement regarding the incidence of acute chest syndrome. Only 12 out of 39 patients initiated on HU for acute chest syndrome had a recurrent attack during a follow up period of 3–7 years. The laboratory parameters were consistent with previous reports: significant increase in hemoglobin level, fetal hemoglobin (HbF) level, Mean Corpuscular Volume, whereas significant decrease in platelet, absolute neutrophil, and absolute reticulocytic counts. All 142 patients tolerated the treatment well. Observed side effects included abdominal pain, dizziness, rash, tremor in one patient each. Of note, 21 patients (11.1%) developed neutropenia (ANC<1000 × 10̂9/l) while 7 patients (3.7%) had thrombocytopenia (<100 × 10̂9/l) which interrupted the treatment for period ranging from 3 weeks to 3 months only. Conclusion: In SCD patients with background of ethnic neutropenia, lower starting dose and limited range of dose escalation of HU ensured safety and yet did not affect efficacy. Disclosures: No relevant conflicts of interest to declare.

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