Evaluation of Splenic Function in Infants with Sickle Cell Anemia in the BABY HUG Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3587-3587
Author(s):  
Zora R. Rogers ◽  
Renee R. Rees ◽  
Winfred C. Wang ◽  
Daner Li ◽  
Rathi V. Iyer ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Geometric Mean ◽  
Organ Damage ◽  
Phase Iii ◽  
Qualitative Assessment ◽  
Splenic Function ◽  
Clinical Complications ◽  
Normal Mean

Abstract Organ damage in children with sickle cell anemia [SCA] begins with the spleen. Hydroxyurea [HU] decreases clinical complications and mortality in severely affected adults with SCA, and has proven hematologic benefits in children. To critically assess the efficacy of HU in preventing chronic organ damage, the Pediatric Hydroxyurea Phase III Clinical Trial [BABY HUG], an NHLBI sponsored double-blinded placebo-controlled multi-center trial, was initiated. One objective of the Feasibility and Safety Pilot is to evaluate novel strategies for assessment of splenic function in young children with SCA. To date 23 subjects (13 male; median age 12.9 mos, range 10.3–17.6 mos) have been recruited without regard to disease severity. Pretreatment spleen function determined by Tc-99m sulfur colloid liver-spleen [LS] scan was compared to pocked erythrocyte [PIT] counts and flow cytometric quantitation of Howell-Jolly Bodies [HJB]. Results were correlated with total [Hgb] and % fetal [HbF] hemoglobin, white blood cell [WBC] and platelet [PLT] counts. Splenic uptake of Tc-99m was qualitatively graded as normal, decreased, or absent by two nuclear medicine physicians. Of 17 LS scans reviewed 3 had normal (mean age 12.2 mos) and 14 decreased (mean age 14.6 mos) spleen function. LS scans were also imaged quantitatively by determining the geometric mean total counts over the spleen. Although there was a trend for qualitative LS scan results to discriminate splenic function among patients (p=.08), quantitative spleen counts demonstrated a stronger relationship between lower uptake and reduced splenic function. A logarithmic transformation was applied to each measure (except age) to improve linearity with other variables and stabilize the variance of the transformed data. PIT counts (p<.0001) and WBC counts (p=.023) were significantly linearly associated with age. Age was inversely related to Hgb (p=.005) and %HbF (p=.009), but not associated with PLT (p=.54) or HJB (p=.38). Quantitative spleen counts were related inversely to age (p<.01), PIT counts (p=.02), and WBC (p=.026); linearly to %HbF (p=.0003) and Hgb (p=.04); and had no relationship with HJB (p=.39) or PLT (p=.68). In multivariate analysis with age and PIT counts, the decline in spleen counts had the strongest association with %HbF (p=.006). A PIT count of 3.5%, which classically divides normal from decreased spleen function, separated spleen counts into significantly different groups (p<.001). No similar relationship existed for HbF 25% (p=.059), Hgb 8 g/dl (p=.15), or HJB 300/million rbc (p=.28). These preliminary data indicate that the decline of splenic function with age in young children with SCA can be effectively assessed by multiple techniques in a multi-center study. Compared to the traditional qualitative assessment, quantitative evaluation of the LS scan will allow more informative gradation of the decline in splenic function for the BABY HUG study. Surrogate measures such as PIT counts and %HbF are associated with LS scan results, and may prove to be informative non-invasive markers predictive of splenic function.

Pharmacokinetics of Hydroxyurea in Young Children with Sickle Cell Anemia: A Report from the BABY HUG Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3184-3184 ◽  
Author(s):  
Zora R. Rogers ◽  
Bruce Thompson ◽  
Russell E. Ware ◽  
Winfred C. Wang ◽  
Rathi V. Iyer ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Limit Of Detection ◽  
Pilot Trial ◽  
Phase Iii ◽  
Response To Treatment ◽  
Capsule Formulation ◽  
Double Blind ◽  
Age Related

Abstract There is a paucity of pharmacokinetic (PK) data about hydroxyurea (HU) in persons with sickle cell anemia (SCA) and none in very young children. HU clearance is predominantly renal. The kidney may be damaged during infancy in SCA, but the first abnormality is usually hyperfiltration which may lead to enhanced HU clearance. Following a 15 mg/kg oral dose of commercially available HU capsules, PKs in 7 adults with SCA and normal renal function have been reported to be a mean±SD half-life (T1/2) of 3.14±0.9 hrs, a maximal concentration (Cmax) of 28.32±11.0 ug/mL, and an area under the curve (AUC) of 81.66±15.5 ug•hr/mL. The Phase II Study of HU in adults concluded that initial 2 hour clearance of HU was not associated with either the maximum tolerated dose or fetal hemoglobin response to treatment. However, the AUC did predict HU toxicity and, in another study, the need for dose adjustment in adults with SCA and renal insufficiency. BABY HUG is an NHLBI-NICHD sponsored Pediatric Phase III Clinical Trial designed to critically assess the efficacy of a novel liquid HU preparation in preventing organ damage in young children with SCA. Forty-five African-American infants, 12 to 18 months (mo) of age (mean 14.7 mo) were recruited without regard to disease severity to the just completed randomized, double-blind, placebo-controlled BABY HUG Feasibility and Safety Pilot Trial. First dose PKs were obtained 0, 1, 2, and 4 hours after oral administration of 20 mg/kg of HU in 22 consecutive patients (mean age 14.5 mo), coincident with measurement of glomerular filtration rate (GFR) by nuclear medicine DTPA clearance. An additional PK sample was obtained between 4 and 8 hours in 15 of the 22 (68%). Samples were frozen at −70°C, shipped, and assayed by high resolution gas chromatography with mass spectrometric detection (limit of detection 0.5 ug/mL). The T1/2 (2.36±0.99 hrs), Cmax (19.81±5.8 ug/mL; 0.26±0.8 uM/L), and AUC (68.82±11.5 ug•hr/mL) were somewhat lower in BABY HUG patients than in the small group of adults with SCA from the literature. There were no apparent relationships between PKs and baseline GFR measured by DTPA or calculated from the Schwartz equation. Younger patients ≤15 mo (n=15) had a trend toward a shorter T1/2 (2.1 vs 2.8 hours; p=0.118) and a lower predicted measurable HU concentration at 8 hours (1.2 vs 2.1 ug/mL; p=0.056) than those 16–18 mo (n=7). There were no age related differences in AUC (67.4 vs 71.8 ug•hr/mL; p=0.421) or Cmax (20.5 vs 18.2 ug/mL; p=0.409). PKs of this novel liquid preparation of HU in young children with SCA may be different than that of adults with the standard capsule formulation. The BABY HUG Trial will continue to refine the PK model by additional evaluations including samples from patients as young as 9 mo of age, the new lower age of eligibility for the open study currently accruing patients.

TCD in Infants: A Report from the BABY HUG Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 952-952 ◽  
Author(s):  
Robert J. Adams ◽  
Julio Barredo ◽  
Duane R. Bonds ◽  
Clark Brown ◽  
James Casella ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Maximum Flow ◽  
Organ Damage ◽  
Sample Volume ◽  
Phase Iii ◽  
Mean Velocity ◽  
Increased Risk ◽  
The Mean ◽  
The Right

Abstract Transcranial Doppler (TCD) is useful in children with sickle cell anemia (SCA) to detect increased risk of stroke. The use of TCD in infants less than 2 years of age is less well established, but has previously been shown to be feasible. As a secondary endpoint in the BABY HUG Trial, TCD is expected to provide useful information on the possible effects of hydroxyurea (HU) in babies with SCA. BABY HUG is an NHLBI-NICHD sponsored phase III clinical trial to compare hydroxyurea to placebo to ascertain effectiveness in preventing end organ damage of the spleen and kidney. Eligible subjects underwent a baseline TCD using the Nicolet Companion (EME) 2-MHz pulsed Doppler. All infants were 8–18 months of age at enrollment, had no history of stroke and were not receiving chronic blood transfusions. Blood flow velocities were recorded using the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol with the exception of reducing the standard sample volume to 4 mm. No sedation was used. The time averaged maximum mean was measured to determine the highest velocity on either side to categorize the study as normal (all recordings &lt;170 cm/sec), conditional (170–199cm/sec) or abnormal (≥200 cm/sec). Recordings of the middle cerebral artery (MCA) and internal carotid artery (ICA) bifurcation defined an adequate TCD. TCD was not required for study entry but subjects with an abnormal exam were not eligible for randomization and treatment. TCD exams were read by blinded reviewers at the Medical College of Georgia. TCD results were transmitted to Clinical Trials & Surveys Corporation (C-TASC) for statistical analysis. As of June 24, 2005, 70 TCD exams had been attempted. Two exams were unsuccessful (no data) because of the children’s irritability and 1 was interpreted as inadequate. Of the remaining 67 TCD exams, 66 were normal and one baby had a high conditional TCD (190 cm/sec). No subjects were found ineligible for the study due to TCD results. The mean velocity of the left MCA was 117 cm/sec ±22.9 and that of the right MCA was 114 cm/sec ±24.9. Regression analyses were performed to examine the relationship of maximum flow velocity (VMAX) to age and total hemoglobin (Hb). VMAX was inversely correlated to Hb (left p=&lt;0.0001, right=&lt;0.0014) and directly associated with age (left p=&lt;.0005, right p=&lt;0.0022). When the mean MCA velocity was regressed against age and Hb, both age (p=0.0285) and Hb (p=.0024) were significant. Adequate baseline TCD evaluation was obtained on 67 out of 70 babies. As expected, baseline TCD velocities varied inversely with the degree of anemia and directly with age; all but one was normal by childhood sickle cell disease standards. These studies provide valuable normative data for infants with SCA, and for further assessment of the effect of HU on TCD in infants with SCA as the study progresses.

Efficacy of Hydroxyurea To Prevent Organ Damage in Young Children with Sickle Cell Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3386-3386 ◽  
Author(s):  
Courtney D. Thornburg ◽  
Natalia Dixon ◽  
Shelly Burgett ◽  
Nicole A. Mortier ◽  
Sherri A. Zimmerman ◽  
...  
Keyword(s):  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Brain Mri ◽  
Organ Damage ◽  
Study Entry ◽  
Acute Chest Syndrome ◽  
Time Interval ◽  
Splenic Sequestration ◽  
Increased Risk

Abstract Hydroxyurea (HU) prevents many acute complications of sickle cell anemia (SCA) in adults and children, but its potential to delay or prevent chronic organ damage has not been defined. The objectives of this prospective IRB-approved study were to assess the safety and efficacy of HU in young children with SCA (age 18 mon–5 years) and to determine whether 2 years of therapy preserves renal function, reduces transcranial doppler ultrasound (TCD) values, and prevents development of brain ischemia as evidenced by magnetic resonance imaging/angiography (MRI/MRA). Fourteen children with SCA (11 male, 3 female; mean age 35±11 mon) enrolled and underwent evaluation including blood counts, %HbF measurement, determination of the glomerular filtration rate (GFR) by radionuclide DTPA clearance and Schwartz estimate, TCD mean cerebral artery (MCA) velocities, and brain MRI/MRA. HU was started at 20 mg/kg/day and escalated by 5mg/kg/day every 8 weeks to a maximum tolerated dose (MTD) or 30 mg/kg/day (mean dose 28±4 mg/kg). Children were evaluated initially every 4 weeks. All baseline tests were repeated at study exit (mean time 25±3 months). HU was tolerated well by all children. Hematological changes occurred as expected, with significant increases observed in hemoglobin concentration, MCV, and %HbF and significant decreases in reticulocytes, WBC, and neutrophils. The average GFR value did not rise as expected in this age range; the DTPA GFR decreased by 5.1 mL/min/1.73 m2 (p=0.26) with only 3 of 11 exit studies exceeding 150 mL/min/1.73 m2 and the Schwartz estimate increased by 16.5 mL/min/1.73 m2 (p=0.17). During HU therapy, the average TCD values significantly decreased with a mean decrease of 26±28 cm/sec in the right MCA (p<.01) and mean decrease of 27±33 in the left MCA (p<.05). At study entry, 3 children had conditional TCD velocities, but all were normal at study exit. One child had mild small vessel ischemic changes on MRI at study entry that were unchanged at study exit. Two children had mild MRA changes that were stable or improved at the end of the study. All children had normal or improved rates of growth and development during therapy. Two children required PRBC transfusion for acute events (acute chest syndrome and hypoplastic anemia during a viral illness). There was one episode of Moraxella catarrhalis bacteremia that was unrelated to myelosuppression and responded to antibiotic therapy. One child was removed from study at week 82 due to the development of thrombocytopenia and hypersplenism, another had acute splenic sequestration but continued HU without recurrence, and a third child with previous acute splenic sequestration did not have recurrence during the study. In conclusion, HU therapy appears to be well tolerated in young children with SCA. In addition to providing beneficial changes in hematological parameters, HU has salutary effects on both the kidney and brain. HU therapy was associated with a stable GFR value during a time interval when hyperfiltration develops, and led to significant decreases in TCD velocities. However, preservation of splenic tissue could lead to an increased risk of splenic complications. Follow-up studies are warranted to determine if long-term HU therapy can preserve or restore organ function in this patient population.

Influence of Hemoglobin Level on Clinical Findings In Infants with Sickle Cell Anemia: Data From BABY HUG

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1631-1631 ◽  
Author(s):  
Jeffrey D. Lebensburger ◽  
Scott T Miller ◽  
Thomas H. Howard ◽  
James F. Casella ◽  
R. Clark Brown ◽  
...  
Keyword(s):  
Platelet Count ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Organ Damage ◽  
Hemoglobin Level ◽  
Phase Iii ◽  
Acute Chest Syndrome ◽  
Severe Anemia ◽  
Laboratory Findings ◽  
Baseline Hemoglobin

Abstract Abstract 1631 Introduction: Infants with sickle cell anemia (SCA) are at risk for organ damage and clinical events. Risk may vary depending on steady state hemoglobin level. BABY HUG (ClinicalTrials.org, NCT00006400), a NHLBI-NICHD supported phase III randomized placebo-controlled trial, examined the ability of hydroxyurea (HU) to reduce end organ damage to the kidneys and spleen and attenuate other complications of SCA in infants. In this secondary study, we investigated whether placebo-treated subgroups defined by extremes of baseline hemoglobin level differed from one another in frequency of sickle cell-related complications and other laboratory findings, and then compared these data to the entire group of infants treated with HU. Methods: BABY HUG subjects randomized at ages 9 – 18 mo were treated with hydroxyurea (20 mg/kg/d) (N=96) or with placebo (N=97) for 2 years. Those randomized to placebo were classified according to their age-adjusted baseline hemoglobin level and subgroups in the lowest (n=24) and highest (n=24) quartiles compared. (Demarcating Hb values were: age 9 to <12 mo, <8.0 vs. >10.2gm/dL; age12 – 18 mo, <8.1 vs. >9.9gm/dL.) Results: BABY HUG primary endpoints of spleen (splenic uptake of 99mTc sulfur colloid on liver-spleen scan) and kidney (GFR by DTPA clearance) function did not differ in placebo group subjects who were in the lowest and highest quartile hemoglobin levels. However, those in the lowest hemoglobin quartile had a higher incidence of acute chest syndrome (ACS) than those in the highest quartile (0.31 vs. 0.02 events/person-year, RR 14.4, p=0.01) and this difference was significantly attenuated by HU (0.05 events/person-year). The relative risk for developing a pain crisis did not differ between the two placebo subgroups (2.2 vs. 2.1 events/person-year), but HU significantly reduced pain frequency compared to either subgroup (0.94 events/person-year, p<0.001). Subjects in the lowest hemoglobin quartile had higher baseline mean TCD velocities than those in the highest quartile (126.2 vs. 112.4 cm/sec, p=0.008). These differences persisted over the two-year period of study, with exit values of 164.9 and 139.6 cm/sec, respectively (p=0.003). By comparison mean TCD velocity in the HU-treated group was 124.5 cm/sec at baseline and 145.6 at exit. Results of neurocognitive testing were not statistically different between groups; however, a trend toward a lower performance developmental index (PDI, p=0.07), but not a lower mental development index (MDI, p=0.15), was observed in subjects with the lowest hemoglobin levels. Subjects in the lowest quartile also had a higher mean WBC (18.0 vs. 11.4 × 109/L, p<0.001), absolute neutrophil count (5.3 vs. 3.6 × 109/L, p=0.001), and platelet count (416 vs. 315 × 109/L, p=0.0001) compared to those with the highest hemoglobin. The laboratory findings of patients receiving HU also were significantly lower than those of subjects in the lowest hemoglobin group and similar to those in the highest hemoglobin group. Conclusions: Severe anemia in very young patients with SCA was associated with elevated WBC and platelet counts and higher TCD velocities. Interestingly, severe anemia also was associated with increased frequency of ACS, in contrast to the association of ACS with higher hemoglobin levels in older patients. Future studies will need to confirm this relationship and clarify to what extent associated findings (e.g., hyposplenia, elevated WBC or platelet count) contribute to this susceptibility. Severe anemia in young SCA patients is a negative prognostic factor that is significantly impacted by early hydroxyurea therapy. Disclosures: Off Label Use: Hydroxyurea is not approved by FDA for infants with sickle cell disease. Miller:NIH/NHLBI; Emmaus Med Inc, Novartis Pharmaceutical; St Jude Childrens Hospital: Research Funding.

Urine Concentrating Ability in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1413-1413
Author(s):  
Scott T. Miller ◽  
Winfred C. Wang ◽  
Rathi V. Iyer ◽  
Sohail R Rana ◽  
Peter A. Lane ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Study Drug ◽  
Organ Damage ◽  
Phase Iii ◽  
Urine Specimen ◽  
Double Blind ◽  
Young Infants ◽  
Paired Serum Sample ◽  
Urine Concentrating Ability

Abstract A urine concentrating defect is quite common in sickle cell anemia (SCA), has its onset in early childhood, and may be reversible (with transfusion) until age 10 years. BABY HUG is an NHLBI-NICHD sponsored double-blind, placebo-controlled Phase III Clinical Trial (NCT00006400) designed to assess efficacy of hydroxyurea in preventing organ damage in young children with SCA (Hb SS or SβO thalassemia); primary endpoints are spleen function and glomerular filtration rate (GFR). Two hundred thirty-three infants, recruited without regard to disease severity, underwent eligibility screening. To assess urine concentrating ability as a secondary endpoint, parents were instructed to collect and save timed urine specimens from subjects after 4 to 10 hours of fluid deprivation (NPO) overnight for osmolality (OSM) determination. More prolonged deprivation was avoided due to safety concerns. A paired serum sample for OSM, urea nitrogen (BUN), and creatinine was obtained the next morning. All specimens were analyzed in a central laboratory. The analyses included 184 infants with a urine specimen and a reported period of fluid deprivation of at least four hours; 178 had concurrent sera. Mean age was 13.0±2.7 mo (range 7.5 – 17.9 mo) and mean duration of fluid deprivation was 7.4±2.4 hr (4–13 hr). Mean serum OSM was 286±6 mOsm/kg H2O and independent of age, height, weight, or duration NPO. Urine OSM (mean 410±152, median 433, range 58–794 mOsm/kg H2O) was significantly greater than serum osmolality (p&lt;0.0001) and correlated with duration NPO (p=0.001). One hundred forty-two infants (77.2%) concentrated urine (urine OSM &gt; [mean serum OSM + 1 SD]); twenty-two (12.0%) had urine/serum OSM ratio &gt; 2 and 54 (29.4%) had urine OSM &gt; 500 mOsm/L. In addition, five infants (2.7%) were isosthenuric (urine OSM within mean serum OSM ± 1 SD) and 37 (20.1%) hyposthenuric (&gt; 1 SD below mean serum OSM) despite instructions to withhold fluid. Urine OSM was associated with increasing 99mTc-DTPA GFR (p=0.024) and BUN (p&lt;0.0001), but not with serum OSM, age, height, weight or serum creatinine. We conclude that even with a variable, often limited, fluid deprivation challenge, 75 percent of young infants with SCD were able to concentrate urine. We anticipate that at the end of each infant’s two-year study drug treatment period parents will be more successful in achieving the recommended fluid deprivation and urine collection and that differences in concentrating ability between those taking hydroxyurea and those taking placebo will be discernable.

scholarly journals A pilot study of hydroxyurea to prevent chronic organ damage in young children with sickle cell anemia

2009 ◽  
Vol 52 (5) ◽  
pp. 609-615 ◽  
Author(s):  
Courtney D. Thornburg ◽  
Natalia Dixon ◽  
Shelly Burgett ◽  
Nicole A. Mortier ◽  
William H. Schultz ◽  
...  
Keyword(s):  
Pilot Study ◽  
Young Children ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Organ Damage

Renal Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1414-1414 ◽  
Author(s):  
Russell E. Ware ◽  
Renee C. Rees ◽  
Sharada A. Sarnaik ◽  
Rathi V. Iyer ◽  
Ofelia A. Alvarez ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hematological Parameters ◽  
Univariate Analysis ◽  
Glomerular Hyperfiltration ◽  
Phase Iii ◽  
Acute Chest Syndrome ◽  
Controlled Clinical Trial ◽  
Splenic Function ◽  
Schwartz Equation

Abstract BABY HUG is an NHLBI/NICHD-sponsored Phase III randomized double-blinded placebo-controlled clinical trial (NCT00006400) to test the hypothesis that hydroxyurea can prevent chronic organ damage in very young children with sickle cell anemia (SCA). Renal and splenic function measures are the co-primary endpoints. Renal disease in SCA begins early in life with impaired urine concentration and acidification, along with glomerular hyperfiltration; some patients will progress to microalbuminuria, glomerulosclerosis, macroalbuminuria, and even renal failure. In BABY HUG, glomerular filtration rate (GFR) elevation was selected as a primary endpoint, to be measured quantitatively by plasma clearance of injected 99mTc-DTPA and also estimated by the Schwartz equation where GFR = (height × 0.55)/(serum creatinine), with creatinine measured by HPLC to .01 mg/dL precision. Of 233 enrolled subjects, 193 completed screening and were randomized to study treatment. Quantitative GFR measurement was successful in most cases: 176 of 182 (97%) of DTPA clearance studies were adequate and 157 subjects had both baseline DTPA and Schwartz GFR values available for analysis. The average age at GFR measurement was 13.7 ± 2.6 months (range 9–19 months) and 59% of subjects were female. Baseline mean (± 1SD) hematological parameters included hemoglobin = 9.0 ± 1.4 gm/dL, absolute reticulocytes = 295.3 ± 137.4 × 109/L, WBC = 14.3 ± 5.8 × 109/L, and fetal hemoglobin (HbF) = 25.6 ± 8.8%. Baseline past medical history included dactylitis (34%), splenic sequestration (7%), and acute chest syndrome (5%). The average baseline quantitative GFR measurement determined by DTPA clearance was elevated at 125.4 ± 34.4 mL/min/1.73m2, (range 40.2 – 300.9 mL/min/1.73m2, normal value 100 ± 20 mL/min/1.73m2). The average baseline GFR estimate by Schwartz equation was substantially higher at 193.9 ± 53.8 mL/min/1.73m2, range 65.8 – 350.0 mL/min/1.73m2. In univariate analysis, the DTPA GFR value was positively correlated with the Schwartz GFR estimate (r=0.22, p=0.0059, slope=0.145) as well as age, weight, height (all p≤.001) but not with hemoglobin, HbF, WBC, reticulocytes, previous sickle cell-related events, or measures of splenic function including liver-spleen scan and quantitation of pitted erythrocytes and micronuclei. The Schwartz GFR estimate was positively correlated with age, height, WBC, and splenic function, and negatively correlated with hemoglobin and HbF. Using a quantitative GFR threshold of 120 mL/min/1.73m2 and an age threshold of 15 months, higher GFR values were observed in older infants, p=0.026. These data indicate that renal dysfunction measured by GFR elevation may begin early in life in SCA; quantitative GFR measurement is feasible but highly variable in this very young patient population; (3) the Schwartz and DTPA GFR values are strongly correlated, but the Schwartz estimate is usually greater and only modestly agrees with the quantitative DTPA GFR value. These baseline GFR measurements in BABY HUG support the hypothesis of age- and disease-related glomerular hyperfiltration in SCA. BABY HUG should yield important information regarding the ability of hydroxyurea to prevent renal damage among infants with SCA.

scholarly journals Patients with Sickle Cell Disease in Sicily Have Lower Rates of End Organ Damage, Allo-Immunization and Opioid Prescription Compared to a US Cohort

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3664-3664
Author(s):  
Caterina Minniti ◽  
Concetta Perrotta ◽  
Di Raimondo Francesco ◽  
Alessandra Quota ◽  
James G. Taylor
Keyword(s):  
Health Care ◽  
Disease Severity ◽  
Sickle Cell ◽  
Access To Health Care ◽  
African Ancestry ◽  
Organ Damage ◽  
Opioid Use ◽  
Clinical Complications ◽  
The Us ◽  
Organ Complications

Abstract Background: In developed countries, childhood mortality in sickle cell disease (SCD) is less than 5%, where the SCD morbidity and mortality burden has shifted to adults. As age increases, so do end organ complications like chronic pain. Environmental factors like health economics and genetic factors may influence such outcomes. Recent data from UK, showed higher than expected survival (ASH 2015) in the setting of a national health care system. The Hospital of Gela, Sicily has a well characterized Caucasian SCD population, which also has consistent access to health care via a nationalized system. We hypothesized that traditional disease severity markers including end organ damage, the rate of red blood cell (RBC) alloimmunization and opioid use would be lower in Sicily, compared to a modern US population of African ancestry with inconsistent access to healthcare. Methods: 90 SCD patients in Sicily were followed for over 9 years (2006-2014) to identify clinical complications, alloimmunization rates and survival. Demographics and sickle and alpha globin genotypes were documented. In the US, 632 SCD patients (excluding those with SC) had the same parameters collected as part of the Bethesda Sickle Cell Cohort Study. Laboratory and clinical complications were compared between populations according to phenotype groups (SS/SB0 or SB+ thalassemia). Clinical manifestations included hospitalizations for pain per year, RBC alloimmunization, hydroxyurea prescription rate. Statistical analysis utilized univariate comparisons (t and Chi square tests). Results: In Sicily, 51 patients had SS/SB0 and 28 SB+. All were of self-described Caucasian ancestry. No SC patients were identified in Sicily, therefore all comparisons were limited to SS/SB0 and SB+ thalassemia. Sicilian SS/SB0 patients were older than the US (p<0.0001), had lower AST (p=0.04) and creatinine (p=0.005), and higher HbF (p<0.0001). SB+ patients had similar characteristics (Table 1). Sixteen Sicilian patients (18%) died at a mean age of 53 years (range 31-77). As suggested by these survival data, SCD complications were less frequent for both SS/SB0 and SB+ groups in Sicily compared to the US (Table 2). More Sicilians were prescribed hydroxyurea, especially among those with SB+, although this was not a significant difference. The pain crisis hospitalizations per year was also higher in the US (p=0.008). Consistent with less frequent hospitalizations, only 4 of the Sicilian patients (3 SS/SB0, 1 SB+) were taking long acting opioids, compared to more frequent opioid use in the US. Finally, RBC alloimmunization, another surrogate measure for disease severity, was twice as common in SS/SB0 patients from the US (30%) as in Sicily (14%, p=0.01). Conclusions: These data suggest that end organ complications, like chronic pain and alloimmunization, in self-described Caucasians with uniform access to health care in Sicily, are less common than in a US cohort of adults. These differences could be attributable to access to specialized care, genetic differences in the proportion of African ancestry or environmental factors like more frequent use of preventative therapies like hydroxyurea. RBC alloimmunization in Sicily is significantly lower than reported in the US , but is still higher than observed in thalassemics in Italy. Perhaps this could be explained a matched genetic background between blood donors and recipients in Sicily, as has been suggested as a strategy to reduce RBC alloimmunization in the US. Further studies comparing unique SCD populations from different geographic regions may be helpful to elucidate genetic or environmental risk factors for end organ complications and disease severity. Table 1. Table 1. Table 2. Table 2. Disclosures No relevant conflicts of interest to declare.

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