scholarly journals The Evaluation of Transfusion Data from the Phase 3 Clinical Study of L-Glutamine in Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3116-3116
Author(s):  
Hung Lam ◽  
Joseph M Becerra ◽  
Charles W Stark ◽  
Yutaka Niihara ◽  
Michael Callaghan
Keyword(s):  
Placebo Group ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Bootstrap Method ◽  
Recurrent Event ◽  
Cumulative Number ◽  
Cell Disease ◽  
Phase 3 ◽  
The Mean ◽  
Rbc Transfusion

Abstract Introduction The multicenter trial of L-glutamine in sickle cell disease enrolled a total of 230 patients, randomized 2:1, to receive L-glutamine (152 patients) or placebo (78 patients). Following 48 weeks of therapy, patients in the L-glutamine group had significantly fewer pain crises and fewer hospitalizations than those in the placebo group. Two thirds of the patients in both trial groups received concomitant hydroxyurea. The Multicenter Study of Hydroxyurea showed that the treatment group differed from the placebo group in the number of units of blood transfused and in the number of patients receiving transfusions. 1 Since an evaluation of transfusions was not pre-specified in the L-glutamine study, post-hoc analyses were performed on the number of units of red blood cells (RBC) transfused and on the number of transfusions that took place during the study. Methods For the number of units of RBCs transfused through Week 48, analyses of the transfusion dataset were performed using the Poisson regression model with both a robust error variance method and a bootstrap method with baseline reticulocyte count as a covariate. The bias-corrected and accelerated bootstrap method was based on 10,000 draws with replacement from the original data used to compute the 95% confidence interval (CI) for relative risk of the number of units of RBCs transfused and the p-value. For the number of transfusion episodes, the recurrent-event time analysis using the Lin-Wei-Yang-Ying (LWYY) method was employed to model the mean cumulative number of RBC transfusion episodes over the 48-week treatment period with baseline reticulocyte count as a covariate. 2 Results There was a significant difference in the number of units of RBCs transfused in the L-glutamine treatment arm than in the placebo arm; 2.86 units per patient-year in the L-glutamine group vs. 5.38 units per patient-year in the placebo group (Table 1). There was a lower trend in the mean cumulative number of RBC transfusion episodes in the L-glutamine arm than the placebo arm during the 48-week treatment period; 1.702 RBC transfusion episodes per patient-year in the L-glutamine arm compared to 2.659 RBC transfusion episodes per patient-year in the placebo arm (Table 2, Figure 1). Conclusion The post-hoc analyses of the L-glutamine phase 3 clinical study in SCD indicated that, of patients requiring RBC transfusions, those assigned to L-glutamine required approximately 43% fewer units of RBCs compared to those assigned to placebo over the 48-Week period. The recurrent event-time analysis showed a favorable trend in the fewer number of RBC transfusion episodes for those receiving L-glutamine as compared to placebo. These observations are significant when considering the fact that 66% of participants in both arms of this study were on hydroxyurea therapy. REFERENCES 1) Niihara Y, Miller ST, Kanter J, et al. A phase 3 trial of L-glutamine in sickle cell disease. N Eng J Med. 2018;379:226-35. 2) Lin DY, Wei LJ, Yang I, Ying Z. Semiparametric regression for the mean and rate functions of recurrent events. J Royal Statistical Society Series B. 2000;62(4):711-30. Figure 1 Figure 1. Disclosures Becerra: Emmaus Medical, Inc: Current Employment. Stark: Emmaus Medical, Inc: Current Employment. Niihara: Emmaus Lifesciences, Inc.: Current Employment. Callaghan: Agios Pharmaceuticals: Current Employment; BioMarin: Consultancy; Chiesi: Consultancy; Forma: Consultancy; Global Blood Therapeutics: Consultancy, Speakers Bureau; Hema Biologics: Consultancy; Kedrion: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Speakers Bureau; Sanofi: Consultancy; Spark: Consultancy; Takeda: Consultancy, Speakers Bureau; uniQure: Consultancy.

scholarly journals Phase 3 Study of L-Glutamine in Sickle Cell Disease: Analyses of Time to First and Second Crisis and Average Cumulative Recurrent Events

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 685-685
Author(s):  
Yutaka Niihara ◽  
Rafael Razon ◽  
Suvankar Majumdar ◽  
Brian Claggett ◽  
Onyinye C. Onyekwere ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Treatment Effect ◽  
Recurrent Events ◽  
Recurrent Event ◽  
Cell Disease ◽  
Employment Equity ◽  
Phase 3 ◽  
Hazard Ratios ◽  
Equity Ownership

Abstract Background A Phase 3, double-blind, randomized, placebo-controlled trial of L-glutamine in 230 patients (ages 5-58) over 48 weeks was conducted at 31 centers in the United States. Twice daily oral administration of L-glutamine or placebo was based on body weight approximating 0.3 g/kg/dose. The primary endpoint was the number of sickle cell crises (SCCs) during 48 weeks of follow-up. The treatment effect measured was the difference of two median numbers of SCCs between two arms by week 48. The SCCs required treatment with I.V. narcotics/ketorolac at an emergency department or during hospitalization in patients with a history of ≥ 2 crisis from the previous year. Splenic sequestration, acute chest syndrome and priapism were also considered to be SCCs. Patients stabilized on hydroxyurea (HU) treatment for at least 3 months prior to study screening (66% in both arms of the study) remained on HU for the duration of the study. The primary analysis via a Cochran-Mantel-Haenszel (CMH) test statistic showed a highly significant treatment effect (p=0.005). There was a median of 3 crises for the L-glutamine treatment arm and 4 for the placebo arm (25% difference). There were no concerning adverse events from the treatment compared with the placebo arm. In this abstract, we reported the results from additional analyses of times to first and second crisis as well as cumulative recurrent events, which further demonstrated the clinically meaningful treatment effect of L-glutamine. Methods The Kaplan-Meier estimates are constructed with the data from the times to the first and second SCC for both arms. The corresponding estimates of the hazard ratios with confidence intervals and p-values are obtained to evaluate the relative merit of two groups. The 50% quartile (median) of the curve and the 95% confidence interval were reported by treatment. Furthermore, recurrent event time analysis was also performed using the Andersen-Gill procedure as well as the robust method by Lin, Wei, Yang and Ying to estimate the intensity rates. Results L-glutamine therapy significantly prolonged the time to first and the time to second SCCs. The median time to first crisis was delayed by 30 days (84 days vs. placebo 54 days; p=0.0152) and the median time to second crisis was delayed by 79 days (212 days vs. placebo 133 days; p=0.0260). Hazard ratios for the time to first and second crisis were similar (0.69 and 0.68 respectively), suggesting an approximately 30% hazard reduction from the treatment (Figures 1 and 2). Both cumulative recurrent event analyses models for SCCs yielded an intensity rate ratio of 0.75 with 95% confidence intervals based on the Andersen-Gill of (0.62, 0.90) and Lin, Wei, Yang and Ying of (0.55, 1.01), respectively (Figure 3). This suggested that the average cumulative crisis count was reduced by approximately 25% over the entire 48-week period. Cumulative event curve separation was clear by day 30 of treatment and was maintained over the 48-week study period. Conclusion The results of the primary endpoint using time to event analytical methods substantiated the original CMH test result that L-glutamine treatment provided clinical benefit in reducing crises, and other acute complications of sickle cell disease, in patients 5 years of age and older irrespective of hydroxyurea use. EndariTM (L-glutamine oral powder) is now FDA-approved to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. Disclosures Niihara: Emmaus Medical, Inc: Employment, Equity Ownership. Razon: Emmaus Medical, Inc: Employment. Wood: Emmaus Medical, Inc: Employment, Equity Ownership. Singh: Emmaus Medical, Inc: Employment. Tran: Emmaus Medical, Inc: Employment, Equity Ownership. Stark: Emmaus Medical, Inc: Employment, Equity Ownership.

scholarly journals Prevalence and Predisposing Factors of Atrial Fibrillation in a Multi-Ethnic Society: The Impact of Racial Differences in Bahrain

2011 ◽  
Vol 4 ◽  
pp. OJCS.S8032 ◽  
Author(s):  
Taysir Garadah ◽  
Saleh Gabani ◽  
Mohamed Al Alawi ◽  
Ahmed Abu-Taleb
Keyword(s):  
Atrial Fibrillation ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Middle Eastern ◽  
Predisposing Factors ◽  
Cell Disease ◽  
Clinical Events ◽  
History Of ◽  
The Mean ◽  
One Year

Background The prevalence and epidemiological data of atrial fibrillation (AF) among multi-ethnic populations is less well studied worldwide. Aim Evaluation of the prevalence and predisposing factors of AF in patients who were admitted to acute medical emergencies (ER) in Bahrain over the period of one year. Methods Two hundred and fifty three patients with onset of AF were studied. The mean difference of biochemical data and clinical characteristics between Middle Eastern (ME) and sub continental (SC) patients was evaluated. The odds ratio of different predisposing factors for the development of clinical events in AF patients was assessed using multiple logistic regression analysis. Results Out of 7,450 patients that were admitted to ER over one year, 253 had AF based on twelve leads Electrocardiogram (ECG), with prevalence of 3.4%. In the whole study, the mean age was 59.45 ± 18.27 years, with 164 (65%) male. There were 150 ME patients (59%), and 107 (41%) SC, 55 (22%) were Indian (IND) and 48 (19%) were South Asian (SA). In the whole study clinical presentation was of 48% for palpitation, pulmonary edema was of 14%, angina pectoris on rest of 12%, 10% had embolic phenomena, 6% had dizziness, and 7% were asymptomatic. The odds ratio of different variables for occurrence of clinical events in the study was positive of 2.2 for history of hypertension, 1.8 for sickle cell disease, 1.2 for high body mass index (BMI) >30, 1.1 for mitral valve disease. The ME patients, compared with SC, were older, had significantly higher body mass index, higher history of rheumatic valve disease, sickle cell disease with high level of uric acid and lower hemoglobin. The history of hypertension, DM and smoking was higher among the SC patients. The rate of thyroid disease was equal in both groups. Conclusion The prevalence of atrial fibrillation was 3.4% with male predominance of 65%. Patients of sub continental origin were younger with a significantly high history of hypertension and ischemic heart disease. The patients of Middle Eastern origin had significantly high rate of rheumatic heart disease, and sickle cell disease. The history of hypertension was the most important independent clinical predictor of adverse events in patients presented with AF.

scholarly journals Ischemic Stroke in Children and Young Adults with Sickle Cell Disease (SCD) in the Post-STOP Era

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 68-68 ◽  
Author(s):  
Janet L. Kwiatkowski ◽  
Julie Kanter ◽  
Heather J. Fullerton ◽  
Jenifer Voeks ◽  
Ellen Debenham ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Cell Disease ◽  
Clinical Series ◽  
The Mean

Abstract Background: The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for children with abnormal TCD as standard of care. To identify children at high-risk of stroke, annual TCD screening is recommended from ages 2 to 16 years, with more frequent monitoring if the result is not normal. A reduction in stroke incidence in children with SCD has been reported in several clinical series and analyses utilizing large hospital databases when comparing rates before and after the publication of the STOP study in 1998. We sought to determine the rate of first ischemic stroke in a multicenter cohort of children who had previously participated in the STOP and/or STOP 2 trials and to determine whether these strokes were screening or treatment failures. Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3,835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 ranged from a single screening TCD to randomization. STOP 2 also had an observational arm for children on CRCT for abnormal TCD whose TCD had not reverted to normal. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both trials. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3,539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 (depending on site) including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two vascular neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results, reviewed source records to confirm all ischemic strokes, defined as a symptomatic cerebral infarction; discordant opinions were resolved through discussion. For the first Post-STOP ischemic stroke, prior TCD result and treatment history subsequently were analyzed. Results: Of the 3,539 subjects, follow-up data were available for 2,850 (81%). Twelve children who had a stroke during STOP or STOP2 were excluded from these analyses resulting in data on 2,838 subjects. The mean age at the start of Post-STOP was 10.5 y and mean duration of follow-up after exiting STOP/2 was 9.1 y. A total of 69 first ischemic strokes occurred in the Post-STOP observation period (incidence 0.27 per 100 pt years). The mean age at time of stroke was 14.4±6.2 (median 13.8, range 3.5-28.9) y. Twenty-five of the 69 patients (36%) had documented abnormal TCD (STOP/2 or Post-STOP) prior to the stroke; 15 (60%) were receiving CRCT and 9 (36%) were not (treatment data not available for 1 subject). Among the 44 subjects without documented abnormal TCD, 29 (66%) had not had TCD re-screen in the Post-STOP period prior to the event; 7 of these 29 (24%) were 16 y or older at the start of Post-STOP, which is beyond the recommended screening age. Four of the 44 (9%) patients had inadequate TCD in Post-STOP (1 to 10.7 y prior to event). Six (14%) had normal TCD more than a year before the event (1.2 - 4 y); all but one of these children were younger than 16 y at the time of that TCD. Only 5 (11%) had a documented normal TCD less than 1 year prior to the event. Conclusions: In the Post-STOP era, the rate of first ischemic stroke was substantially lower than that reported in the Cooperative Study of Sickle Cell Disease, prior to implementation of TCD screening. Many (39%) of the Post-STOP ischemic strokes were associated with a failure to re-screen according to current guidelines, while only 11% occurred in children who had had recent low-risk TCD. Among those known to be at high risk prior to stroke, treatment refusal or inadequate treatment may have contributed. While TCD screening and treatment are effective at reducing ischemic stroke in clinical practice, significant gaps in screening and treatment, even at sites experienced in the STOP protocol, remain to be addressed. Closing these gaps should provide yet further reduction of ischemic stroke in SCD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Sexual Maturity in Adolescents Suffering from Sickle Cell Disease: A Cross-sectional Study

2021 ◽  
Author(s):  
Vijay Shah ◽  
Akash Patel ◽  
Praful Bambharoliya ◽  
Jigisha Patadia
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sexual Maturity ◽  
Tanner Stage ◽  
Cross Sectional Study ◽  
Reproductive Capacity ◽  
Sectional Study ◽  
Cell Disease ◽  
Cross Sectional ◽  
The Mean

Introduction: Sickle Cell Disease (SCD) is an inherited chronic haemolytic anaemia. The diseased person suffers from various complications such as anaemia, frequent infection, fever, hand-foot syndrome, stroke, etc. Puberty changes includes the appearance of the secondary sexual characteristics, increase in height, change in body composition and development of reproductive capacity. Aim: To study the sexual maturity and effect of multiple blood transfusions in adolescents suffering from SCD. Materials and Methods: It was a cross-sectional study conducted on 35 adolescents of age group 11 to 15 years, suffering from SCD. Study was conducted over a period of six months from March 2018 to September 2018 at Department of Paediatrics. SCD was diagnosed by Haemoglobin (Hb) electrophoresis. Weight and height were measured of all the participants. For assessing the sexual maturity, Tanners staging was used. Unpaired t-test was done for data analysis. Results: The mean age of the patients was 13.03±1.7 years. There were 25 males and 10 females. The mean age of male patients between Tanner stage 2(14.63±0.52 years) and Tanner stage 3 (14.75±0.5 years) was significantly higher than the Indian data for males (11.3 and 12.8 years, respectively). The mean age of female patients between Tanner stages 2 (13.5±2.12 years) and Tanner stage 3 (14.33±1.16 years) was higher than the Indian reference data for girls (10.2 and 11.6 years respectively). Conclusion: This study concluded that adolescents with SCD were significantly shorter in height and weight than the standard reference population. Sexual maturity is delayed in adolescents with sickle cell anaemia.

scholarly journals Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq

Anemia ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zeina A. Salman ◽  
Meaad K. Hassan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Readmission Rate ◽  
Length Of Hospital Stay ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Opioid Use ◽  
Asthma Symptoms ◽  
The Mean ◽  
High Readmission Rate

Objectives. Despite improvements in the management of sickle cell disease (SCD), many patients still experience disease-related complications requiring hospitalizations. The objectives of this study were to identify causes of hospitalization among these patients and factors associated with the length of hospital stay (LOS) and readmission.Methods. Data from 160 patients (<14 years old) with SCD who were admitted to the Basra Maternity and Children’s Hospital from the first of January 2012 through July 2012 were analyzed.Results. The main causes of hospitalization were acute painful crises (73.84%), infections (9.28%), acute chest syndrome (8.02%), and acute splenic sequestration crisis (6.32%). The mean LOS was4.34±2.85days. The LOS for patients on hydroxyurea (3.41±2.64days) was shorter than that for patients who were not (4.59±2.86days),P<0.05. The readmission rate (23.1%) was significantly higher among patients with frequent hospitalizations in the previous year (OR 9.352, 95% CI 2.011–43.49), asthma symptoms (OR 4.225, 95% CI 1.125–15.862), and opioid use (OR 6.588, 95% CI 1.104–30.336). Patients on hydroxyurea were less likely to be readmitted (OR 0.082, 95% CI 0.10–0.663).Conclusions. There is a relatively high readmission rate among patients with SCD in Basra. The use of hydroxyurea significantly decreases the LOS and readmission rate.

Sickle cell crisis as evaluated from measurements of hydroxybutyrate dehydrogenase and myoglobin in plasma.

1981 ◽  
Vol 27 (2) ◽  
pp. 314-316 ◽  
Author(s):  
E F Roth ◽  
P A Bardfeld ◽  
S J Goldsmith ◽  
E Radel ◽  
J C Williams
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
High Specificity ◽  
Mean Value ◽  
Cell Disease ◽  
Sickle Cell Crisis ◽  
The Mean ◽  
Low Sensitivity ◽  
Sickle Cell Crises

Abstract Data on plasma hydroxybutyrate dehydrogenase activity (I) and myoglobin concentration were used to evaluate painful sickle cell crises. I was increased during non-crisis steady state in patients with sickle cell disease as compared to normal values (232, SD 79.7 vs 85, SD 33 Sigma units/mL). During crisis, the mean value for I increased further to 379 (SD 139) Sigma units/mL. For 12 patients evaluated both during steady state and crisis, there was a mean increase in plasma I of 131% (SD 76%). Repeated determinations of I in sickle cell disease patients during several months while they were in steady state showed that baseline I varied by no more than 20% from the mean. Plasma myoglobin in patients with sickle cell disease was not above normal, but during crisis 21 of 39 patients tested had increased plasma myoglobin concentrations. Our data suggest that I may be a useful indicator of sickle cell crisis when the patient's own baseline value is available for comparison. Plasma myoglobin measurements give evidence of muscle damage during crisis with high specificity but low sensitivity.

scholarly journals Beneficial effects of adenotonsillectomy in children with sickle cell disease

2020 ◽  
Vol 6 (4) ◽  
pp. 00071-2020
Author(s):  
Ilaria Liguoro ◽  
Michele Arigliani ◽  
Bethany Singh ◽  
Lisa Van Geyzel ◽  
Subarna Chakravorty ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Beneficial Effects ◽  
Admission Rates ◽  
The Mean ◽  
The Impact

Tonsillectomy and adenoidectomy (T&A) is frequently performed in children with sickle cell disease (SCD). Our aim was to evaluate the impact of this surgery on overnight oxygenation and rates of complications in these patients.Children with SCD who underwent T&A between 2008 and 2014 in two tertiary hospitals were retrospectively evaluated. Overnight oximetry and admission rates due to vaso-occlusive pain episodes (VOEs) and acute chest syndrome (ACS) in the year preceding and following the surgery were compared.19 patients (10 males, 53%) with a median age of 6 years (range 3.5–8) were included. A significant increase of mean overnight arterial oxygen saturation measured by pulse oximetry (SpO2) (from 93±3.6% to 95.3±2.8%, p=0.001), nadir SpO2 (from 83.0±7.1% to 88±4.1%, p=0.004) and a reduction of 3% oxygen desaturation index (from a median value of 5.7 to 1.8, p=0.003) were shown. The mean annual rate of ACS decreased from 0.6±1.22 to 0.1±0.2 events per patient-year (p=0.003), while the mean cumulative rate of hospitalisations for all causes and the incidence of VOEs were not affected.T&A improved nocturnal oxygenation and was also associated with a reduction in the incidence of ACS at 1-year follow-up after surgery.

Timing of the Initiation of Hydroxyurea and Hematologic Outcomes in Patients with Sickle Cell Disease (SCD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1004-1004
Author(s):  
Shaina Willen ◽  
Nirmish Shah ◽  
Courtney Thornburg ◽  
Jennifer Rothman
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Significant Relationship ◽  
Medical Center ◽  
Fetal Hemoglobin ◽  
Clinical Severity ◽  
Cell Disease ◽  
Younger Age ◽  
The Mean

Abstract Abstract 1004 Hydroxyurea (HU) is approved for use in adults with Sickle Cell Disease (SCD) and increases the production of fetal hemoglobin (HbF). Increased HbF is associated with decreased clinical severity in adults and children with SCD, such as decreased numbers of vaso-occlusive events, transfusions, and hospitalizations. Higher HbF at initiation of HU is predictive of HbF response, but association between age of hydroxyurea initiation and HbF response has not been investigated. We hypothesize that starting hydroxyurea at an early age may improve hematological and clinical response. In order to determine if younger age at hydroxyurea initiation affects the percentage of HbF achieved with hydroxyurea, we conducted a retrospective cohort study. We identified subjects enrolled in the Duke University Medical Center Comprehensive Sickle Cell program who initiated hydroxyurea when they were less than 17.99 years of age and were prescribed hydroxyurea for at least six months. The following data were abstracted from the medical record between December 1996 and April 2011: age, hemoglobin, percentage HbF, and mean corpuscular volume (MCV) at start of HU and at maximum tolerated dose (MTD) of HU therapy. The correlation coefficient and p-values for various parameters were calculated. Seventy-three patients (41 males and 32 females) were included in the analysis. The mean age at hydroxyurea initiation was 5.5 years (1.2–14.1). The mean hydroxyurea dose at MTD was 28.6 ± 3.2 mg/kg/day. At initiation, the mean hemoglobin was 8.2 ± 1.2 g/dL, the mean MCV was 83±7.4 fl and mean HbF was 10 ± 5.7%. At MTD, the mean hemoglobin was 9.4 ± 1.1 g/dL, the mean MCV was 99 ± 11.1 fl, and the mean HbF was 21.7 ± 9.4%. As expected, at MTD, an elevated MCV was correlated with elevated fetal hemoglobin (r2= 0.19, p= 0.0001) [Table 1]. There was a statistically significant relationship between the age at HU initiation and the HbF at MTD (r2= 0.08, p= 0.015) [Figure 1] as well as the age at HU initiation and the hemoglobin at MTD (r2= 0.19, p= 0.016). The relationship between the age at starting HU and the overall change in HbF (DHbF) was not statistically significant (r2= 0.01, p= 0.41). There was not a statistically significant relationship between age at HU initiation and the MTD of HU (r2= 0.003, p= 0.61). The 6 patients started on HU at age less than 2 years (mean 1.5 ± 0.3 years) maintained a mean elevated HbF of 19.1 ± 5% at last documented follow-up with follow-up ranging from 1.4–13 year of uninterrupted hydroxyurea use. Starting hydroxyurea therapy at a younger age appears to improve HbF response as measured at MTD, although there is variability in the level of fetal hemoglobin attained. There is not an association seen with the DHbF or dose at MTD and age at hydroxyurea initiation. In summary, starting hydroxyurea at a younger age, when HbF is >20%, leads to persistence of HbF production and overall improvement in hematological efficacy. This was not simply the result of achieving MTD at a younger age before physiologic decline of HbF. Disclosures: Off Label Use: Hydroxyurea for complications of sickle cell disease in pediatrics. Shah:Eisai: Research Funding; Adventrx: Consultancy.

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