Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.     

Identification of a gene expression profile associated with operational tolerance among a selected group of stable kidney transplant patients

Despite their utility, immunosuppressive treatments have numerous side effects, including infectious complications, malignancies and metabolic disorders, all of which contribute to long‐term graft loss. In addition to the development of new pharmaceutical products with reduced toxicity and more comfortable modes of administration, tailoring immunosuppression according to the immune status of each patient would represent a significant breakthrough. Gene expression profiling has been shown to be a clinically relevant monitoring tool. In this paper, we have assessed the overall long‐term kidney transplant outcome and attempted to identify operationally tolerant‐like patients among recipients with stable clinical status at least 5 years post‐transplantation. We thus measured a combination of noninvasive blood biomarkers of operational tolerance in a cohort of 144 stable patients and showed that only 3.5% exhibited a gene expression profile of operational tolerance, suggesting that such a profile can be detected under immunosuppressive therapy but that its frequency is low in kidney transplant recipients when compared with liver transplant recipients. We suggest that a rational approach to patient selection, based on a combination of clinical and biological characteristics, may help to provide a safer method for identification of patients potentially suitable for immunosuppressive drug weaning procedures.     

Assessment of stool colour in community management of prolonged jaundice in infancy

Jaundice persisting beyond the first 2 wk of life is often regarded as an indication for investigation to exclude cholestatic liver disease. Most babies with prolonged jaundice have breast milk-related jaundice, which is a benign condition. Cholestatic liver disease is usually accompanied by pale stools and yellow or orange urine. A community programme was established to ascertain the incidence of prolonged jaundice and determine whether abnormal stool and urine colour could be used to assist primary care staff in referral decisions. Data were collected on normal stool and urine colour and used to devise a colour chart and information sheet for parents. Babies with prolonged jaundice were identified and referred for investigation. In all, 3661 babies were recruited into the study, of which 127 were jaundiced at 28 d of age. Of these, 125 were breastfed. The incidence of jaundice in breastfed babies at 28 d was 9.2% (95% CI 7.8%-11.0%) Abnormal liver function tests (LFTs) were common, but no baby had abnormal stool or urine colour and none was found to have liver disease. Jaundiced breastfed babies who are well are unlikely to have serious disease. Elevated LFTs are compatible with a diagnosis of breast milk-related jaundice. Prolonged jaundice in bottle-fed babies, and persistent pallor of stools or yellow/orange urine, are rare and merit immediate referral. Parents and professionals can be advised to report pale stools without generating a large number of unnecessary referrals. Further work is needed to determine whether a colour chart reduces the mean age of referral and treatment of infants with cholestatic liver disease.     

Effects of collagen membranes enriched with in vitro-differentiated N1E-115 cells on rat sciatic nerve regeneration after end-to-end repair

Preventing falls and fall-related fractures in the elderly is an objective yet to be reached. There is increasing evidence that a supplementation of vitamin D and/or of calcium may reduce the fall and fracture rates. A vitamin D-calcium supplement appears to have a high potential due to its simple application and its low cost. However, published studies have shown conflicting results as some studies failed to show any effect, while others reported a significant decrease of falls and fractures. Through a 15-year literature overview, and after a brief reminder on mechanism of falls in older adults, we reported evidences for a vitamin D action on postural adaptations - i.e., muscles and central nervous system - which may explain the decreased fall and bone fracture rates and we underlined the reasons for differences and controversies between published data. Vitamin D supplementation should thus be integrated into primary and secondary fall prevention strategies in older adults.