A double-blind, placebo-controlled phase II study of the efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease.

This placebo-controlled phase II study evaluated the pharmacodynamics, efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), a fetal globin gene-inducing short-chain fatty acid derivative, administered orally at 15 mg/kg twice daily for 48 weeks in 76 subjects with sickle cell disease (SCD). The median age was 26 years (range: 12-55 years) and 37 subjects (49%) were treated previously with hydroxycarbamide. Sixty subjects (79%) had Hb SS and 16 (21%) had S/ß(0) thalassemia. The study was terminated after a planned interim analysis showed no significant increase in fetal hemoglobin (Hb F) and a trend for more pain crises in the HQK-1001 group. For 54 subjects with Week 24 data, the mean absolute increase in Hb F was 0.9% (95% confidence interval (CI): 0.1-1.6%) with HQK-1001 and 0.2% (95% CI: -0.7-1.1%) with placebo. Absolute increases in Hb F greater than 3% were noted in 9 of 38 subjects (24%) administered HQK-1001 and 1 of 38 subjects (3%) administered placebo. The mean changes in hemoglobin at Week 24 were comparable between the two groups. The mean annualized rate of pain crises was 3.5 with HQK-1001 and 1.7 with placebo. The most common adverse events in the HQK-1001 group, usually graded as mild or moderate, consisted of nausea, headache, vomiting, abdominal pain, and fatigue. Additional studies of HQK-1001 at this dose and schedule are not recommended in SCD. Intermittent HQK-1001 administration, rather than a daily regimen, may be better tolerated and more effective, as shown previously with arginine butyrate, and warrants further evaluation.

Prolonged chronic phase of greater than 10 years of chronic myelogenous leukemia in a patient with congenital human immunodefeciency virus infection.

A 15-year-old male with congenital HIV infection was diagnosed with chronic myelogenous leukemia (CML) at age 4 years 9 months. HIV was initially treated with zidovudine. For the last >10 years he has received didanosine, lamivudine, and nelfinavir. CML was treated with Interferon alfa (INF-alpha) for >10 years and a brief course of hydroxyurea (HU). He remained in chronic phase CML since diagnosis however recent molecular monitoring revealed increased BCR/ABL transcripts necessitating a change in therapy to imatinib. The very prolonged chronic phase of CML in this patient has been unexpected especially in light of the underlying congenital HIV infection.

Electron-beam CT as a diagnostic modality in pediatric nephrology and renal transplant surgery.

Electron-beam computed tomography is an imaging technology with a variety of medical applications, primarily in cardiology due to its sub-second acquisition time enabling visualization of a beating heart. Recently, this technique has also been introduced into other fields because of lower radiation exposure compared to traditional computed tomography, as well as the strengths of post-procedural three-dimensional visualization. This report evaluates electron-beam computed tomography as a diagnostic modality in pediatric nephrology patients. Seven patients reflecting typical clinical scenarios in pediatric nephrology were reviewed with regard to the value of electron-beam computed tomography and its contribution to the diagnostic workup. Electron-beam computed tomography is noninvasive and allows three-dimensional post-processing, enabling highly accurate images while requiring less radiation and acquisition time. It is very useful for clinical questions that require a detailed description of vascular and renal anatomy.