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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Journal of Pediatric Hematology/Oncology Vol. 33, No. 7 ( 2011-10), p. e300-e303
    In: Journal of Pediatric Hematology/Oncology, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 7 ( 2011-10), p. e300-e303
    Type of Medium: Online Resource
    ISSN: 1077-4114
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 2047125-7
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  • 2
    In: Gastroenterology, Elsevier BV, Vol. 136, No. 5 ( 2009-5), p. A-511-
    Type of Medium: Online Resource
    ISSN: 0016-5085
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
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  • 3
    In: Pediatric Transplantation, Wiley, Vol. 25, No. 4 ( 2021-06)
    Abstract: FA is the most common cause of inherited BMF syndromes. The only cure for BMF in FA remains HSCT. Due to DNA instability in FA, RIC has been used to decrease immediate and late complications of HSCT. Most FA conditioning regimens in mismatched and unrelated donor transplants rely on TBI, which increases the risk of secondary malignancies. Most of the non‐TBI conditioning regimens use an ex vivo T‐cell depletion approach, but this is not feasible at all pediatric stem cell transplant programs. To evaluate the success of HSCT in patients with FA using non‐TBI conditioning regimens with in vivo T‐cell depletion approach. HSCT using non‐TBI based conditioning was performed on two siblings with FA. The first sibling underwent matched unrelated donor transplant with a BM graft using fludarabine, alemtuzumab, busulfan, and cyclophosphamide conditioning and cyclosporine and mycophenolate as GVHD prophylaxis. The second sibling underwent MSD transplant with UCB and BM grafts using similar approach, but without busulfan and mycophenolate. Both siblings had engraftment without signs of acute or chronic GVHD. Acute post‐transplant complications included brief viral reactivations. At last follow‐up, both siblings continued to have full immune reconstitution with stable chimerism. Conditioning regimens without radiation and inclusion of alemtuzumab can lead to successful engraftment without development of GVHD and reduce risk of developing secondary neoplasms, even with unrelated donor transplants.
    Type of Medium: Online Resource
    ISSN: 1397-3142 , 1399-3046
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2008614-3
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  • 4
    In: Clinical Endocrinology, Wiley, Vol. 52, No. 4 ( 2000-04), p. 463-469
    Type of Medium: Online Resource
    ISSN: 0300-0664
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    Language: English
    Publisher: Wiley
    Publication Date: 2000
    detail.hit.zdb_id: 2004597-9
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  • 5
    In: Pediatric Blood & Cancer, Wiley, Vol. 50, No. 4 ( 2008-04), p. 864-866
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 2130978-4
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  • 6
    In: Pediatric Blood & Cancer, Wiley, Vol. 65, No. 8 ( 2018-08)
    Abstract: Paclitaxel, ifosfamide, cisplatin (TIP) is commonly used as salvage for malignant germ cell tumors (MGCT) in adults; however, additional administration of cisplatin at a young age could cause significant short‐ and long‐term toxicities in a group of patients with high expected salvage. Because carboplatin has been shown to be effective in pediatric MGCT with less toxicity, the TIP regimen was modified by substituting carboplatin for cisplatin. Methods The Children's Oncology Group conducted a phase II trial between November 2007 and June 2011 evaluating “TIC” (paclitaxel 135 mg/m 2 /day Day 1, ifosfamide 1,800 mg/m 2 /dose Days 1–5 and carboplatin with AUC 6.5 Day 1) in children  〈  21 years with relapsed MGCT. The endpoint of the trial was response after two cycles, incorporating RECIST response and marker decline. Results Twenty patients (12 male, median age 13.5 years) were enrolled. Seventeen patients had tumor markers ≥10 times above normal. After two cycles, by RECIST criteria, 8 patients achieved a partial response (response rate 40%), 10 had stable disease, and 2 had progressive disease. A ≥ 1 log reduction was achieved in 10/17 patients (58.8%) with elevated markers. By study defined criteria, combining response by RECIST and marker decline, the response rate was 44%. Conclusion TIC is active in relapsed pediatric MGCT and should be considered for salvage therapy in children. In adolescents and older adults with relapse MGCT, TIP or high‐dose chemotherapy with stem cell remain the standard therapy.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2130978-4
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  • 7
    Online Resource
    Online Resource
    American Academy of Pediatrics (AAP) ; 2008
    In:  Pediatrics Vol. 121, No. 4 ( 2008-04-01), p. 777-782
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 121, No. 4 ( 2008-04-01), p. 777-782
    Abstract: OBJECTIVES. The objectives of this study were (1) to determine the prevalence and risk factors of elevated pulmonary artery pressures in children with homozygous SS or Sβ° thalassemia using Doppler echocardiography and (2) to determine a correlation between abnormal transcranial Doppler examinations and elevated pulmonary artery pressures. METHODS. Screening echocardiograms were prospectively performed during an annual comprehensive clinic visit on children who were older than 6 years and had homozygous SS or Sβ° thalassemia. Detailed history, examination, and laboratory tests were done, and transcranial Doppler examinations were obtained in children 2 to 14 years of age. Pulmonary hypertension was defined as pulmonary artery systolic pressure of at least 30 mmHg corresponding to a peak tricuspid regurgitant jet velocity of ≥2.5 m/second. Mild pulmonary hypertension was defined as tricuspid regurgitant jet velocity ≥2.5 to 2.9 m/second. Moderate pulmonary hypertension was defined as tricuspid regurgitant jet velocity ≥3 m/second. Patients with pulmonary stenosis or right outflow obstruction were excluded. Characteristics were compared between patients with mild, moderate, and no pulmonary hypertension using 1-way analysis of variance for continuous variable and Fisher's exact test for categorical variables. RESULTS. Of the 75 patients who had homozygous SS/Sβ° thalassemia and were older than 6 years, echocardiograms were obtained for 62 (82.6%). Thirty percent (19 of 62) of patients had elevated tricuspid regurgitant jet velocity ≥2.5 m/second. One third of these patients had tricuspid regurgitant jet velocity ≥3 m/second. All patients with elevated tricuspid regurgitant jet velocity had SS disease. A high reticulocyte count, low oxygen saturation, and a high platelet count were significantly associated with elevated pulmonary artery pressures. There was no difference in age, gender, history of acute chest syndrome, hydroxyurea therapy, chronic blood transfusion, stroke, hemoglobin, and bilirubin between patients with and without elevated pulmonary artery pressures. A total of 47% patients with elevated tricuspid regurgitant jet velocity and 57% without elevated tricuspid regurgitant jet velocity had screening transcranial Doppler examinations. Transcranial Doppler examinations were normal for all patients. CONCLUSIONS. High pulmonary artery pressures do occur in children with sickle cell disease. Screening by echocardiography can lead to early detection and intervention that may potentially reverse this disease process. There was no correlation between elevated pulmonary artery pressures and abnormal transcranial Doppler examination in our study.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2008
    detail.hit.zdb_id: 1477004-0
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  • 8
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2240-2240
    Abstract: Background: Pain crisis is the most frequent reason for admission in children with sickle cell disease (SCD). Frequent hospitalizations are associated with school absenteeism, emotional distress, and financial hardships. There is limited literature on initiatives to decrease admissions and hospital days in SCD pain crises. Prior studies have shown that individualized pain plans in emergency rooms can decrease admission rates and that a multidisciplinary approach with provider and patient education and close follow up can decrease 30-day readmission rates. Our goal was to decrease hospital days for pain crisis admissions by 40% over a 5-year period using a multidisciplinary approach. Methods: From September 2011 to August 2016 a multidisciplinary quality improvement project was conducted. A Plan-Do-Study-Act methodology was used. Five key drivers were identified and nine interventions were implemented. Interventions for the entire cohort included individualized home pain plans, emergency room and inpatient order sets, inpatient daily schedules, and a psychoeducation and biofeedback program. High utilizers, defined as ≥ 4 admissions per year, had an individualized SCD plan and were assigned a mental health provider. The high utilizer group was expanded to include at risk patients (3 admissions per year). Data was analyzed for all patients age 0-21 years admitted for SCD pain crises. The primary measure was hospital days, with 30-day readmission rate as a balancing measure. Results: 216 SCD patients were followed in 2011, with a 14% increase over the five year study period. From this cohort, a total of 122 patients were admitted for pain crises during this time. 48% of admitted patients were male, with a mean age of 10.68±5.65 years, and 72% had hemoglobin SS disease (16% SC, 5% Sβ0, 7% Sβ+). As shown in Table 1, the number of patients admitted decreased from 55 patients (25.4% of total SCD patients) in the pre-intervention period to 33 patients (13.3% of total SCD patients) in the final year of the intervention (p = 0.0014). The number of admissions decreased from 148 admissions in the pre-intervention period to 86 admissions in the final year of the intervention (54.7% decrease). The number of hospital days decreased by 61% from 59.6 days per month in the pre-intervention period to 23.2 days per month in the final year of the intervention (p 〈 0.0001). Number of high utilizers decreased from 13 patients in the pre-intervention period to 7 patients in the final year of the intervention. There was a 66% reduction in the number of hospital days in the high utilizer group compared to a 47% reduction in the low utilizer group. The 30-day readmission rate decreased from 33.9% pre-intervention to 19.4% in the final year of intervention. Special cause variation was first achieved in April 2014, 18 months after the start of all interventions, with a shift of the centerline from 59.6 days/month to 38.3 days/month and again in February 2016 with a decrease to 23.2 days/month (Figure 1). There was special cause variation in 30-day readmissions in April 2014 with a centerline shift in the 30-day readmission rate from 33.9% to 19.4%. The baseline direct hospital cost for SCD admissions was $909,000 per year. In the final year of the project, the average cost was $353,880 per year, with an overall annual savings of $555,120 in direct hospital costs. Conclusion: In this single center study, the multidisciplinary approach of effective home, emergency room, and inpatient pain management combined with increased mental health services for higher risk individuals proved to be effective in decreasing SCD pain crisis admissions and hospital days. A dedicated team effort with simple interventions had a significant impact on the well-being of the entire SCD population, but especially those who were more frequent utilizers of the healthcare system, while decreasing hospital costs, and can serve as a model for other institutions. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 9
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2641-2641
    Abstract: Abstract 2641 Abstract: Only few genes appear to strongly regulate HbF levels in adults with sickle cell disease (SCD). We aim to: (1) Extend these observations to children with SCD, who likely have better preserved marrow capacity; (2) Assess whether these same genes and other previously identified candidates (Ma et al., 2007) associate with HbF response to HU. Methods: We performed a retrospective analysis from 6 sites (see author affiliations) of children age 5–21 with HbSS or HbS-B thalassemia, untreated with HU or treated for 〉 6 months at comparable indications and dosing, using %HbF at steady state (baseline) and on HU at or near maximal tolerated dose (MTD), defined as 〉 20mg/kg/day. Subject adherence to HU was assessed by report to their hematology clinician. Siblings were excluded to ensure genetic independence. Candidate 36 SNPs from 2 groups of genes were genotyped: 1) those from reported GWAS: 15 SNPs in BCL11A, 3 in HBS1L-MYB intron, 5' site in B globin, plus sar1; and 2) 15 candidate SNPs exhibiting the largest effect size on HbF with HU treatment (Ma, 2007). SNP genotyping (minor allele frequency (MAF) ranging from 0.10 to 0.50) was performed on the Sequenom MassArray iPLEX platform. (SNP sequences are available.) Duplicate samples assured genotype concordance. Genotype frequency distribution at each SNP was tested for deviations from Hardy-Weinberg equilibrium. MAFs were comparable across our 6 sites, to allele frequencies in HapMap for CEU populations, and CSSCD (Lettre et al., 2008), confirming validity of pooling SNP genotype data from the sites. Using HbF as a continuous trait, genetic associations were assessed from a total of 80 children, 29 of whom are on HU, between each of the 36 SNPs and: a) baseline %HbF; b) %HbF on HU treatment; c) delta %HbF (HU treatment - baseline). For each model, linear regression analysis was used to test quantitative trait and disease trait SNP associations assuming an additive effect for each copy of the minor allele on the phenotype. Resultant p-values were assessed for significance using Bonferroni adjustment for multiple testing. Results: Of the 80 children, comparing the 51 not on HU to those 29 on HU, no significance differences were seen in the distribution and average of baseline %HbF (9.2 vs. 8.9, p=0.820). SNP analyses are summarized in Table 1. 8 SNPs were nominally significantly associated with baseline %HbF. Direction of SNP association differed among these SNPs; some MAF may be reversed in this population compared to those previously reported. For %HbF on HU, the B globin SNP was significantly associated. The delta %HbF on HU is significantly associated with the B globin SNP and nominally so with BCLA11 and SAR1A gene. Our preliminary data begin to extend findings of specific genetic variants regulating HbF to children with SCD. Early data suggest that HbF in response to HU may share some of the mechanisms governing baseline HbF in SCD, not surprising given the commonality of enhanced erythropoiesis. Subject recruitment and analyses are on-going. Disclosure: Off Label Use: Hydroxyurea has not been FDA approved for use in children with sickle cell disease, a topic of the submitted abstract.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 4841-4841
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4841-4841
    Abstract: Abstract 4841 Background: Pulmonary hypertension (PHT) is a significant complication of sickle cell disease. Studies in children report a 16–30% prevalence of elevated pulmonary artery pressures, as estimated by measurement of tricuspid regurgitant jet velocity (TRV) on echocardiography. The pathogenesis of elevated pulmonary artery pressures is multifactorial, with hemolysis induced endothelial dysfunction playing a major role. More recent studies highlight the role of inflammation in the pathogenesis. Hydroxyurea is a well established treatment for sickle cell disease. It acts primarily by induction of fetal hemoglobin, thereby reducing hemolysis, with possible additional effects on vascular and endothelial function. The aim of this study was to determine if early detection and treatment with hydroxyurea will decrease elevated pulmonary artery pressures in children with sickle cell disease. Methods: The study was conducted at 3 centers. Children with Hb SS and Hb Sb0 thalassemia between the ages of 5–21 years, with a screening echocardiogram showing a TRV ≥ 2.5 m/sec were identified. An echocardiogram was repeated to confirm elevated TRV. Subjects with persistent elevation of TRV ≥ 2.5 m/sec on repeat echocardiogram, were consented and started on hydroxyurea at 20 mg/kg/d with escalation to a maximum tolerated dose or a total daily dose of 30 mg/kg/d. Laboratory data and echocardiograms were repeated at 6 and 12 months to measure effect of hydroxyurea on TRV. Additionally blood and urine samples were also collected pre treatment, at 6 and 12 months post treatment for biomarker analysis, which will be performed later. Baseline and 6 month laboratory and echocardiogram data were compared using paired t test. Results: Twelve patients were enrolled. Mean age was 12.25 years (range 6–19 years) with a M:F ratio of 2:1. Average follow up is 11 months. Patients tolerated hydroxyurea well, and in 90% of patients the dose was escalated to 30 mg/kg/d. 1 patient achieved MTD at 20 mg/kg/d. Two patients went off study at 4 and 5 months respectively. As shown in Table 1, six months after starting hydroxyurea there was a significant increase in mean oxygen saturation, hemoglobin, mean corpuscular volume and fetal hemoglobin. There was a significant decrease in mean reticulocyte count, LDH and white blood cell count. There was no significant change in TRV six months after treatment with hydroxyurea. Conclusion: Hydroxyurea significantly decreased measures of hemolysis in children with sickle cell disease. Six months after treatment with hydroxyurea, there was no significant change in estimated pulmonary artery pressures measured on echocardiography. The study is ongoing to see if hydroxyurea affects pulmonary artery pressures with a longer duration of treatment. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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