To achieve successful therapeutic outcomes in chronic myeloid leukemia (CML), continuous and adequate imatinib (Gleevec(®), Glivec(®), Novartis Pharmaceuticals, Basel, Switzerland) dosing is essential. Here, we report a patient counseling program ("Care club", "Happy club" in Korea) performed to improve patient compliance with imatinib. From January 2006 to December 2008, patients diagnosed with chronic phase CML and taking imatinb were eligible for this retrospective study. A total of 114 patients from 4 centers in Korea were recruited at a 50:50 ratio for Happy club group versus non-Happy club group at each center. During 36-month follow-up, persistency (the number of days of imatinib prescribed versus 1 year) was higher in the Happy club group (98.2 ± 0.03%) than in the non-Happy club group (79.3 ± 0.16%, P = 0.001), whereas dose compliance (miligrams of imatinib that were actually taken versus miligrams that should have been taken) was not different between two groups; 96.5 ± 0.6% and 96.6 ± 0.7% in the Happy club and non-Happy club (P = 0.958). Overall compliance (the product of persistency and dose compliance) improved in the Happy club group (93.0 ± 2.3%) compared with the non-Happy club group (76.2 ± 7.4%, P = 0.001). The patient counseling program was efficient especially in patients who needed high-dose imatinib (>400 mg/day), and overall compliance was 87.8 ± 6.0% in the Happy club group versus 65.5 ± 16.1% in the non-Happy club group (P = 0.017). In conclusion, the patient counseling program was effective in persisting imatinib medication, resulting in the improvement of overall compliance.
To investigate the correlation of trough imatinib mesylate (IM) levels with cytogenetic or molecular responses, we measured trough IM levels in patients with chronic myeloid leukemia, chronic phase (CML-CP), at 6 months of treatment with a standard dose of IM. Eighty-seven newly diagnosed patients with CML-CP were prospectively enrolled. Seventy-eight patients (89.7%) showed an optimal response (complete or partial cytogenetic response) at 6 months. Trough IM levels were 1378 + 725 ng/mL. When categorized into two groups, there was a statistically significant difference in numbers of patients with optimal and suboptimal responses at 6 months (group with 51000: 80.6% vs. 19.4%; 1000: 94.6% vs. 5.4%; p ¼ 0.032), and in numbers of patients with early major molecular response (early-MMR) and without MMR at 6 months (group with 51000: 3.2% vs. 96.8%; 1000: 21.4% vs. 78.6%; p ¼ 0.047). In conclusion, the incidence of optimal cytogenetic response or early-MMR in patients with CML-CP treated with IM for 6 months was significantly higher in those with a trough level of 1000 compared with those with a level of 51000. Dose escalation of IM can be one option in patients with CML showing suboptimal response or resistance to the standard dose of IM, especially with low trough plasma IM levels (51000 ng/mL).
Mesenchymal stem cells (MSCs) have the capacity to proliferate and differentiate into multiple connective tissue lineages, which include cartilage, bone, and fat. Cartilage differentiation and chondrocyte maturation are required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. This study was designed to identify novel genes that might help clarify the molecular mechanisms of chondrogenesis. Chondrogenesis was induced by culturing human bone marrow (BM) derived MSCs in micromass pellets in the presence of defined medium for 3, 7, 14 or 21 days. Several genes regulated during chondrogenesis were then identified by reverse transcriptase-polymerase chain reaction (RT-PCR). Using an ABI microarray system, we determined the differential gene expression profiles of differentiated chondrocytes and BM-MSCs. Normalization of this data resulted in the identification of 1,486 differentially expressed genes. To verify gene expression profiles determined by microarray analysis, the expression levels of 10 genes with high fold changes were confirmed by RT-PCR. Gene expression patterns of 9 genes (Hrad6B, annexinA2, BMP-7, contactin-1, peroxiredoxin-1, heat shock transcription factor-2, synaptotagmin IV, serotonin receptor-7, Axl) in RT-PCR were similar to the microarray gene expression patterns. These findings provide novel information concerning genes involved in the chondrogenesis of human BM-MSCs.
Allogeneic hematopoietic stem cell transplantation (alloSCT) is currently the only curative treatment modality for myelodysplastic syndromes (MDS). The treatment paradigm for MDS has changed in recent years with the introduction of hypomethylating agents (HMAs). The present retrospective multicenter study was designed to assess the effects of pre-transplant HMA on transplant outcome and determine which patients would benefit most from this therapy. A total of 109 patients who received alloSCT at one of five institutions between 2007 and 2010 were enrolled in this study regardless of pre-transplant HMA therapy. 81 of the 109 patients enrolled were treated with HMA prior to alloSCT. 28 patients received alloSCT without HMA bridging. The distributions of WHO classification groups and IPSS scores were similar between the two groups (P = 0.752 and P = 0.265, respectively). Pre-transplant HMA did not affect OS (P = 0.244), and there were no differences in response to HMA therapy within the HMA-treated group. The cumulative incidence of NRM was not significantly different between the two groups (P = 0.500). However, for patients with a high blast count (>5 % of bone marrow at the time of diagnosis), pre-transplant HMA therapy had a NRM benefit (83.3 vs. 48.6 %, P = 0.014).
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