Clinical outcomes of splenectomy in children: Report of the splenectomy in congenital hemolytic anemia registry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110704/1/ajh23888.pd

Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years

BACKGROUND: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality. PROCEDURE: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single- and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor—a first-in-class HbS polymerization inhibitor—in patients aged 6 months to 17 years with SCD. Initial findings from a cohort of 45 patients aged 4 to 11 years who received voxelotor treatment for up to 48 weeks are reported. RESULTS: Hemoglobin (Hb) response, defined as a >1.0 g/dl increase from baseline, was achieved at week 24 by 47% (n = 16/34) of patients with Hb measurements at baseline and week 24. At week 24, 35% (n = 12/34) and 21% (n = 7/34) of patients had a >1.5 g/dl increase and a >2.0 g/dl increase from baseline in Hb concentration, respectively. Concurrent improvements in hemolytic markers were observed. Voxelotor was well tolerated in this young cohort, with no newly emerging safety signals. CONCLUSIONS: Based on its mechanism as an HbS polymerization inhibitor, voxelotor improves Hb levels and markers of hemolysis and has the potential to mitigate SCD-related complications; these results support its use in patients aged ≥4 years

Clinical features of infantile hepatic hemangioendothelioma

PurposeInfantile hepatic hemangioendothelioma (IHHE) is the most common type of hepatic vascular tumor in infancy. We conducted this study to review our clinical experience of patients with IHHE and to suggest management strategies.MethodsWe retrospectively analyzed the medical records of 23 IHHE patients (10 males, 13 females) treated at the Asan Medical Center between 1996 and 2009.ResultsMedian age at diagnosis was 38 days (range, 1 to 381 days). Seven patients (30%) were diagnosed with IHHE based on sonographically detected fetal liver masses, 5 (22%) were diagnosed incidentally in the absence of symptoms, 5 (22%) had congestive heart failure, 3 (13%) had skin hemangiomas, 2 (9%) had abnormal liver function tests, and 1 (4%) had hepatomegaly. All diagnoses were based on imaging results, and were confirmed in three patients by histopathology analysis. Six patients were observed without receiving any treatment, whereas 12 received corticosteroids and/or interferon-alpha. One patient with congestive heart failure and a resectable unilobar tumor underwent surgical resection. Three patients with congestive heart failure and unresectable tumors were managed by hepatic artery embolization with/without medical treatment. At a median follow-up of 29 months (range, 1 to 156 months), 21 (91%) patients showed complete tumor disappearance or >50% decrease in tumor size. One patient died due to tumor-related causes.ConclusionIHHE generally has a benign clinical course with low morbidity and mortality rates. Clinical course and treatment outcome did not differ significantly between medically treated and non-treated groups. Surgically unresectable patients with significant symptoms may be treated medically or with hepatic artery embolization

Hydroxyurea (hydroxycarbamide) for sickle cell disease.

Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review.To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting.We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries.Date of the most recent search: 16 January 2017.Randomised and quasi-randomised controlled trials, of one month or longer, comparing hydroxyurea with placebo, standard therapy or other interventions for people with SCD.Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias.Seventeen studies were identified in the searches; eight randomised controlled trials were included, recruiting 899 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months.Four studies (577 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; three recruited individuals with only severe disease and one recruited individuals with all disease severities. There were statistically significant improvements in terms of pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use), measures of fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. There were no consistent statistically significant differences in terms of quality of life and adverse events (including serious or life-threatening events). Seven deaths occurred during the studies, but the rates by treatment group were not statistically significantly different.Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) compared hydroxyurea and phlebotomy to transfusion and chelation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts, but more occurrences of acute chest syndrome and infections in the hydroxyurea and phlebotomy group. There were no consistent statistically significant differences in terms of pain alteration and adverse events (including serious or life-threatening events). Two deaths occurred during the studies (one in a the hydroxyurea treatment arm and one in the control arm), but the rates by treatment group were not statistically significantly different. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early.The quality of the evidence for the above two comparisons was judged as moderate to low as the studies contributing to these comparisons were mostly large and well designed (and at low risk of bias); however evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events and results are applicable only to individuals with HbSS and HbSβºthal genotypes.Of the remaining two studies, one (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts but no statistically significant differences in terms of adverse events (including serious or life-threatening events).The final study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea - there was statistically significant improvement in terms of measures of fetal haemoglobin, but no statistically significant differences in terms of adverse events (including serious or life-threatening events). No participants died in either of these studies and other outcomes relevant to the review were not reported.The quality of the evidence for the above two comparisons was judged to be very low due to the limited number of participants, the lack of statistical power (as both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes.There is evidence to suggest that hydroxyurea is effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly in preventing chronic complications of SCD, recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with HbSC genotype. Future studies should be designed to address such uncertainties

Etoposide-related cardiotoxicity in a child with haemophagocytic lymphohistiocytosis

AbstractWe report a male child with haemophagocytic lymphohistiocytosis who developed myocardial infarction after receiving etoposide. He recovered well with supportive measures and after discontinuation of etoposide. We discuss the possible mechanisms and differential diagnoses of myocardial infarction in our patient.</jats:p

Measuring success: utility of biomarkers in sickle cell disease clinical trials and care

AbstractProgress in the care of sickle cell disease (SCD) has been hampered by the extreme complexity of the SCD phenotype despite its monogenic inheritance. While epidemiological studies have identified clinical biomarkers of disease severity, with a few exceptions, these have not been routinely incorporated in clinical care algorithms. Furthermore, existing biomarkers have been poorly apt at providing objective parameters to diagnose sickle cell crisis, the hallmark, acute complication of SCD. The repercussions of these diagnostic limitations are reflected in suboptimal care and scarcity of adequate outcome measures for clinical research. Recent progress in molecular and imaging diagnostics has heralded a new era of personalized medicine in SCD. Precision medicine strategies are particularly timely, since molecular therapeutics are finally on the horizon. This chapter will summarize the existing evidence and promising data on biomarkers for clinical care and research in SCD.</jats:p

Epidemiology and Outcome of TRALI and TACO in the Pediatric Population: A Multi-Institutional Review

Abstract Introduction: Transfusion of blood products can be associated with a wide variety of complications ranging in level of severity. The most lethal of these are Transfusion-Associated Circulatory Overload (TACO) and Transfusion-Related Acute Lung injury (TRALI). Over the five year period from 2012-2016, TRALI was the leading cause of transfusion-associated fatalities, closely followed by TACO. However, the incidence of these potentially lethal transfusion reactions in the pediatric population is not well known. Our objective is to describe the incidence of these transfusion reactions in pediatric patients and describe their associated morbidity and mortality. Materials/Methods: We used the Pediatric Health Information System (PHIS), an electronic database of children's hospitals in the USA. Data was obtained from 45 children's hospitals in 2005-2015 for patients ≤ 21 years of age who received transfusion of packed red blood cells, platelets, whole blood, coagulation factors, other serum and exchange transfusion. From this group of patients, we then identified patients who developed TRALI and TACO. Patients were identified by ICD9 codes for transfusion of various blood products and related adverse events. We abstracted data on demographics, medication use, length of stay (LOS), hospital charges and mortality. Results: During the study period, 383,154 inpatient encounters in which patients received a blood product transfusion were identified. Overall the number of blood product transfusions has remained stable (Figure 1). There were 982 transfusion reactions per 100,000 hospital encounters over this period and the incidence rates of each type of transfusion reaction are described in Table 1. In our patient cohort, 108 cases of TRALI and 102 cases of TACO were identified. Cohorts were similar with regards to gender distribution. Distributions of age and race differed between the TRALI and TACO cohorts compared to the all transfusions cohort (Table 2). The morbidity, mortality and hospital charges of encounters complicated by TRALI and TACO are described in Table 3. In the TRALI cohort, a significantly greater number of patients required mechanical ventilation, ECMO or transfer to the ICU and had a greater increase in mortality in comparison to the all transfusion cohort. The TACO cohort had a significantly increased number of patients who required ECMO or ICU transfer compared to the all transfusions cohort. Length of stay was significantly greater for patients in the TRALI cohort compared to the all transfusions cohort. Patients diagnosed with either TRALI or TACO had significantly increased costs associated with hospitalization. Conclusion: Our study demonstrated that both TRALI and TACO are associated with an excess morbidity and mortality. However, the number of cases of TRALI and TACO in our study were fewer than what was expected based on previous studies. This indicates that TRALI and TACO are likely under-diagnosed and under-reported. Efforts should be made to increase awareness of recognizing and reporting of these transfusion reactions to improve the outcome of these potentially lethal complications. Disclosures No relevant conflicts of interest to declare. </jats:sec