The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbS␤°thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P ‫؍‬ .018), and male sex (P ‫؍‬ .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761. IntroductionSilent cerebral infarcts (SCIs) have been recognized by neuroimaging in neurologically normal older adult populations since 1981 1 and were documented in sickle cell anemia (SCA) soon afterward. 2 As with overt stroke, SCIs represent a clinical finding that is common in older adults without SCD, but they appear during early childhood in persons with SCA. SCIs are defined as an MRI signal abnormality visible on 2 views on the T2-weighted images (axial and coronal) that must measure at least 3 mm in one dimension; further, the person deemed to have an SCI must have an absence of focal neurologic deficit compatible with the anatomic location of the brain lesion. 3 SCI is the most common form of neurologic injury among children with SCA, occurring in at least 27% before 6 years of life 4 and 37% by 14 years of life. 5 SCIs in children with SCA are associated with increased risk of future overt strokes and new or progressive SCIs. 6,7 In addition, children with SCA and SCI have been found to have poorer cognitive function The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. 3684BLOOD, 19 APRIL 2012 ⅐ VOLUME 119, NUMBER 16For personal use only. on March 28, 2019. by guest www.bloodjournal.org From than children with SCA with normal MRI of the brain 8-10 or sibling controls. 10,11 Clinical and laboratory risk factors for SCI have been evaluated only sparingly. In the most rigorous study to date, the investigators from the Cooperative Study for Sickle Cell Disease (CSSCD) described risk factors associated with SCI in 42 participants, comparing them with 188 controls with ...

A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.

Measurements using the Acuson system are modestly lower than those obtained with dedicated Doppler using the Nicolet TCD.

Patients with Langerhans cell histiocytosis (LCH) may behave differently depending on what sites are involved and the response or lack of response to earlier therapies. Therapy for high-risk patients or those with multiple reactivations continues to be challenging because of variable response rates and frequent toxicities. The goals of this study were to determine the long-term disease free survival in children with high-risk or multiply reactivated LCH treated with 2-CDA, and the toxicity of low dose continuous infusion (CI). Ten children with multiple reactivations or high-risk disease as defined by the Histiocyte Society were treated with CI 2-CDA and were evaluable for response and toxicity assessment. The starting dose of 2-CDA was 5 mg/M(2)/day for 3 days and escalated to 6.5 mg/M(2)/day for 3 days if tolerated. The maximum number of courses of 2-CDA per patient was limited to six. Fifty-two courses of 2-CDA were administered without difficulty. After the patient demonstrated no acute toxicity with the first administration of 2-CDA, the subsequent doses were given at home to all but one patient. All 10 patients had a clinical response, 9 documented by radiographic, or changes in physical exam or review of systems. Toxicity was limited to myelosuppression. Seven of the 10 patients required no additional therapy and remain disease free a median of 50 months from completing therapy. The three remaining patients are currently disease free after receiving other therapy. Further studies are needed to determine the role of 2-CDA in this patient population. 2-CDA can be given safely using home therapy, and may effective even in high-risk patients.

We conclude that the CRS identifies the patients who are most severely affected with ACS, and that upfront RCE is a safe and effective treatment for these patients. Additional work is needed to develop a method to predict which of the apparently less severely affected patients will fail to improve after simple transfusion and should receive upfront RCE.

Tumor lysis syndrome (TLS) and renal failure remain significant causes of morbidity and mortality in children with newly diagnosed Burkitt's lymphoma and high white blood cell count acute lymphocytic leukemia (ALL) despite conventional management with aggressive hydration, alkalinization, allopurinol, and the slow introduction of chemotherapy. A subgroup of patients at very high risk for TLS and renal failure can be identified based on the level of serum lactate dehydrogenase (LDH) and urine output. We evaluated the prospective use of continuous veno-venous hemofiltration (CVVH), in addition to conventional management to prevent renal failure from tumor lysis, in three children with advanced abdominal Burkitt's lymphoma and in two children with high white blood cell count T-cell ALL who were at very high risk based on LDH and urine output. In this cohort of very high-risk patients, the LDH ratio (value at diagnosis/upper limit of normal) ranged from 0.88 to 10.3 and urine output from 0.13 to 4.7 ml/kg per hour. CVVH was begun at a mean time of 10.5 h before chemotherapy was initiated. Full-dose induction chemotherapy was begun within 24 h of diagnosis. After beginning CVVH, the uric acid levels decreased 46% prior to beginning chemotherapy and decreased to a mean of 4.2 mg/dl 24 h after chemotherapy was initiated. Four of the five patients had either no change or a drop in the serum creatinine. In patient one, blood urea nitrogen peaked at 58 mg/dl, and the creatinine at 4.7 mg/dl 6 days after beginning chemotherapy with a subsequent return to normal. Asymptomatic hypokalemia developed in all patients. After beginning chemotherapy, CVVH was continued for a mean of 85 h (range 70-91 h). No patient had complications secondary to CVVH. In summary, CVVH prevented renal failure secondary to TLS in 80% of these very high-risk patients. In the fifth patient, CVVH allowed full-dose chemotherapy to continue. The prospective use of CVVH could potentially decrease the morbidity and mortality associated with induction chemotherapy in very high-risk patients with a large tumor burden.

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The reading, writing, and vocabulary skills of 8 children with strokes due to sickle cell disease were compared with 8 control children. The former were delayed in reading and writing skills but not in vocabulary development or use.