Suzanne Saccente

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure

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 HbSβ° 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.

Prevention of tumor lysis syndrome using continuous veno-venous hemofiltration.

Tumor lysis syndrome (TLS) and renal failure remain significant causes of morbidity and mortality in children with newly diagnosed Burkitts 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 continous veno-venous hemofiltration (CVVH), in addition to conventional management to prevent renal failure from tumor lysis, in three children with advanced abdominal Burkitts lymphoma and in two children with high white blood cell count T-cel ALL who were at very high risk based on LDH and urine output. In this cohort of very highrisk 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.

Efficacy of continuous infusion 2-CDA (Cladribine) in pediatric patients with Langerhans cell histiocytosis

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/M2/day for 3 days and escalated to 6.5 mg/M2/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.

Comparison of Automated Red Cell Exchange Transfusion and Simple Transfusion for the Treatment of Children With Sickle Cell Disease Acute Chest Syndrome

Both simple transfusion (ST) of packed red blood cells and automated red cell exchange (RCE) are used in the treatment of acute chest syndrome (ACS). We report our experience using each of these modalities for the treatment of ACS.

READING, WRITING, AND VOCABULARY SKILLS OF CHILDREN WITH STROKES DUE TO SICKLE CELL DISEASE

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.