ABSTRACT
Although rituximab has seen increasing use in the treatment of immune thrombocytopenia (ITP) for many years, its therapeutic role in this disease remains unclear. We retrospectively analyzed data of all patients with ITP treated with rituximab (375 mg/m(2) once weekly for four consecutive weeks) and consecutively entered the findings into the databases of six large academic centers in the Czech Republic. A total of 114 patients were included in the analysis. All of the patients received rituximab as a second or additional line of therapy. The overall response rate (ORR) after rituximab therapy was 72 % [48 % complete response (CR), 24 % partial response (PR)] at month 6, and 69 % (45 % CR, 24 % PR) at month 12. For the group of patients with newly diagnosed (acute) ITP, the results of treatment were significantly better than for the group of patients with persistent or chronic ITP; nonetheless, this group of patients was far too small (n = 18) for our findings to be generalized. Multivariate analysis revealed that the ORR was significantly influenced primarily by the number of therapies prior to rituximab (the more previous therapies, the worse treatment response). The results of our analysis "from everyday hematological practice" confirm the high efficiency of rituximab treatment in pretreated adult patients with ITP.
Subject(s)
Antibodies, Monoclonal, Murine-Derived/administration & dosage , Immunologic Factors/administration & dosage , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Middle Aged , Retrospective Studies , RituximabABSTRACT
UNLABELLED: We used microarray profiling to investigate the direct effects of lenalidomide on gene expression in isolated CD14(+) monocytes from 6 patients with del(5q). Our data demonstrate that changes in genes involved the tumor necrosis factor (TNF) signaling pathway and the bone marrow stroma, suggesting that treatment with lenalidomide may help restore the damaged niche and suppress the TNF signaling pathway. BACKGROUND: Lenalidomide is an effective treatment for patients with del(5q) and myelodysplastic syndrome (MDS) The exact mechanism of lenalidomide function and its impact on the prognosis of patients is not known exactly. MATERIALS AND METHODS: We used gene expression profiling to study the effect of lenalidomide therapy in peripheral blood CD14(+) monocytes of 6 patients with del(5q) and MDS. RESULTS: After lenalidomide treatment, genes involved in the tumor necrosis factor (TNF) signaling pathway that were upregulated in the patients before treatment decreased to the healthy control baseline expression level. This change in gene expression, in conjunction with increased expression of repressed genes that affect the stem cell niche (ie, CXCR4 and CRTAP), may exert a positive effect on treated patients. In contrast, we found that increased expression of the ARPC1B gene may have a negative impact on the stability of patient remission. CONCLUSION: The observed changes in gene expression described here may contribute to the identification of pathways that are affected by lenalidomide, which may help to explain the effects of this drug.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 5 , Gene Expression/drug effects , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Thalidomide/analogs & derivatives , Actin-Related Protein 2-3 Complex/genetics , Actin-Related Protein 2-3 Complex/metabolism , Aged , Case-Control Studies , Female , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Lenalidomide , Lipopolysaccharide Receptors/blood , Lipopolysaccharide Receptors/genetics , Lipopolysaccharide Receptors/metabolism , Male , Middle Aged , Monocytes/drug effects , Monocytes/metabolism , Myelodysplastic Syndromes/metabolism , Prognosis , Proto-Oncogene Proteins c-jun/genetics , Proto-Oncogene Proteins c-jun/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Stem Cell Niche/drug effects , Stem Cell Niche/genetics , Thalidomide/therapeutic use , Transcriptome/drug effects , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation/drug effects , Up-Regulation/geneticsABSTRACT
C/EBPalpha (CCAAT/enhancer binding protein alpha) belongs to the family of leucine zipper transcription factors and is necessary for transcriptional control of granulocyte, adipocyte and hepatocyte differentiation, glucose metabolism and lung development. C/EBPalpha is encoded by an intronless gene. CEBPA mutations cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL) patients. In this study we identified in 41 individuals from 824 screened individuals (290 AML patients, 382 MDS patients, 56 NHL patients and 96 healthy individuals) a single class of 23 deletions in CEBPA gene which involved a direct repeat of at least 2 bp. These mutations are characterised by the loss of one of two same repeats at the ends of deleted sequence. Three most frequent repeats included in these deletions in CEBPA gene are CGCGAG (493-498_865-870), GCCAAGCAGC (508-517_907-916) and GG (486-487_885-886), all according to GenBank accession no. NM_004364.2. A mechanism for deletion formation between two repetitive sequences can be recombination events in the repair process. Double-stranded cut in DNA can initiate these recombination events of adjacent DNA sequences.
