ABSTRACT
V617F JAK2 mutation is a reliable molecular marker of polycythemia vera (PV), potentially useful to monitor the effect of treatments in this disease. In a phase 2 study of pegylated (peg) IFN-alpha-2a in PV, we performed prospective sequential quantitative evaluation of the percentage of mutated JAK2 allele (%V617F) by real-time polymerase chain reaction (PCR). The %V617F decreased in 24 (89%) of 27 treated patients, from a mean of 49% to a mean of 27% (mean decrease of 44%; P < .001), and no evidence for a plateau was observed. In one patient, mutant JAK2 was no longer detectable after 12 months. In 3 patients homozygous for the mutation, reappearance of 50% of wild-type allele was observed during treatment. The results seem to confirm the hypothesis that IFN-alpha preferentially targets the malignant clone in PV and show that %V617F assessment using a quantitative method may provide the first tool to monitor minimal residual disease in PV. This trial was registered at www.clinicaltrials.gov as #NCT00241241.
Subject(s)
Interferon-alpha/therapeutic use , Polycythemia Vera/drug therapy , Polycythemia Vera/genetics , Polyethylene Glycols/therapeutic use , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Adult , Aged , Female , Genetic Markers , Humans , Interferon alpha-2 , Janus Kinase 2 , Male , Middle Aged , Point Mutation , Recombinant Proteins , Time FactorsABSTRACT
A 22-year-old woman was admitted in August 2001 for loss of consciousness due to hypoglycemia. Her serum insulin level during the hypoglycemic episode was high at 121 mU/l (normal range: 5-25 mU/l). She had never received an insulin injection. Insulin antibodies by radioimmunoassay were positive. During hospitalisation, the patient presented clinical and biological features of systemic lupus erythematosus (SLE). Treatment with high-dose corticosteroids and cyclophosphamide resulted in restoration of euglycemia associated with resolution of circulating anti-insulin antibodies and parallel improvement in clinical and laboratory features of SLE.
Subject(s)
Autoimmune Diseases , Insulin/immunology , Lupus Erythematosus, Systemic/diagnosis , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adult , Autoantibodies/analysis , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Female , Humans , Hypoglycemia/diagnosis , Hypoglycemia/etiology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Insulin/blood , Insulin Antibodies/analysis , Radioimmunoassay , Syndrome , Time FactorsABSTRACT
Optimal treatment of non operable localized non small cell lung carcinoma (NSCLC) continues to evolve. Increasing overall survival must evolute through improving local tumoral control and eradication of probable occult metastasis. Historically, median survival varies between 7 and 10 months with a standard conventional fractionated radiotherapy (RT). Induction chemotherapy (CT) followed by RT has demonstrated its superiority over RT alone, modality which is widely utilised. Other studies revealed best results with decreasing metastatic relapses. Three independent meta-analysis confirmed benefit obtained with cisplatin based CT followed by RT that allowed to consider this association as a gold standard. Other authors demonstrated an improvement of local control and survival with concomitant RT-CT or hyperfractionated accelerated RT. Results of all of these new therapeutic modalities still poor. Implication of new CT drugs has conducted for an emergence of new studies finding to demonstrate more encouraging results. Randomized trials are conducted in this way.
