Phase 2 trial of intravenously administered plerixafor for stem cell mobilization in patients with multiple myeloma following lenalidomide-based initial therapy.

Initial therapy of multiple myeloma with lenalidomide-based regimens can compromise stem cell collection, which can be overcome with the addition of plerixafor. Plerixafor is typically given subcutaneously (SQ), with collection ∼11 h later for maximum yield. Intravenous administration may allow more rapid and predictable mobilization. This trial was designed to assess the efficacy and feasibility of IV plerixafor in patients receiving initial therapy with a lenalidomide-based regimen. Patients received G-CSF at 10 µg/kg/day for 4 days followed by IV plerixafor at 0.24 mg/kg/dose starting on day 5; plerixafor was administered early in the morning with apheresis 4-5 h later. Thirty-eight (97%) patients collected at least 3 × 10(6) CD34+ cells/kg within 2 days of apheresis. The median CD34+ cells/kg after 1 day of collection was 3.9 × 10(6) (range: 0.7-9.2) and after 2 days of collection was 6.99 × 10(6) (range: 1.1-16.5). There were no grade 3 or 4 non-hematological adverse events, and one patient experienced grade 4 thrombocytopenia. The most common adverse events were nausea, diarrhea and abdominal bloating. IV plerixafor is an effective strategy for mobilization with low failure rate and is well tolerated. It offers flexibility with a schedule of early-morning infusion followed by apheresis later in the day.

Apolipoprotein E, brain injury and neurodevelopmental outcome of children.

Apolipoprotein E plays an important role in neurodegenerative processes in adulthood, whereas its neurodevelopmental role is uncertain. We aimed to study the effect of apolipoprotein E on neurodevelopment in a cohort liable to neurodevelopmental changes. The cohort consisted of very preterm (<32 gestational weeks) and/or very low birth weight (<1500 g) children, and the longitudinal follow-up protocol included sequential cranial ultrasounds during infancy, brain magnetic resonance imaging at term-equivalent age, neurological and cognitive assessment (Mental Developmental Index) at the corrected age of 2 years and cognitive and neuropsychological assessments (Wechsler Preschool and Primary Scale of Intelligence and Developmental NEuroPSYchological Assessment) at the chronological age of 5 years. Apolipoprotein E genotypes were determined from 322 children. Ultrasound and magnetic resonance imaging data were available for 321 (99.7%) and 151 (46.9%) children, respectively. Neurodevelopmental assessment data were available for 138 (42.9%) to 171 (53.1%) children. Abnormal findings in ultrasounds and magnetic resonance imaging were found in 163 (50.8%) and 64 (42.4%) children, respectively. Mild cognitive delay at the corrected age of 2 years and the chronological age of 5 years was suspected in 21 (12.3%) of 171 and 19 (13.8%) of 138 children, respectively. In the Developmental NEuroPSYchological Assessment, 47 (32.6%) of 144 children had significantly impaired performances in more than one study subtest. No associations between the apolipoprotein E genotypes and imaging findings or measured neurodevelopmental variables were found. Apolipoprotein E genotypes do not appear to have major impact on brain vulnerability or neurodevelopment in children.

Hormone therapy and estrogen receptor expression in breast cancer.

Postmenopausal hormone therapy (HT) may increase breast cancer risk and influence tumor characteristics. We investigated 321 postmenopausal women aged 50-65 years, with breast cancer, diagnosed and treated at Radiumhemmet, Karolinska Hospital, during 1993-1997. In women using HT (n =90) estrogen receptor concentration (ER) at diagnosis were lower than in non-users (n =135) (1.17 vs 1.70 fmol/microg; p <0.05). HT users also had a tendency to less multifocal (5 vs 12%) (p <0.05) and metastatic disease (5% vs 2%) however this was not statistically significant. The estrogen receptor expression is always considered in the judgement on hormone dependency and the clinical decision on adjuvant endocrine therapy. A suppression of ER during HT could tentatively influence the treatment decisions in breast cancer patients and maybe disregard patients from endocrine treatment.