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  • American Society of Hematology  (4)
  • 1
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2272-2272
    Abstract: Abstract 2272 To test the correlation of trough plasma Imatinib Mesylate (IM) levels and pharmacogenomic variation with cytogenetic or molecular responses, we measured trough plasma IM levels and analyzed various genetic polymorphisms in newly diagnosed CML patients at 6 months of IM treatment and compared them with the likelihood of achieving cytogenetic complete response (CyCR) or major molecular response to standard dose of IM. Newly diagnosed 94 CML patients were prospectively enrolled in the current study. CyCR was achieved in 71 patients (75.5%). Eighty-four patients (89.4%) showed optimal response (CyCR + cytogenetic partial response CyPR) at 6 months. Trough plasma IM levels were highly variable ranging from 203 to 4980 ng/ml: mean (±SD) was 1392±78.8 ng/ml. Among 47 patients with trough plasma IM level of 〈 1320 ng/ml, 39 patients (83.0%) showed optimal response and 8 (17.0%) suboptimal response. Among 47 patients with trough plasma IM level of ≥1320 ng/ml, 45 patients (95.7%) showed optimal response and 2 (4.3%) suboptimal response (P=0.045). Trough plasma IM level was 1346.0±78.3 ng/ml for the group with non-hematologic toxicity of grade 0 or 1 and 1969.6±365.3 for the group with grade 2–4, which was statistically significant (p=0.038). The impact of single nucleotide polymorphisms (SNPs) in cytochrome P450 (CYP) genes (CYP2D6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2B6, CYP2C8, CYP1A2) and transporter genes (hOCT1, hOCT2, hOCT3, ABCG2, ABCC2, SLCO1B1, ABCB1) potentially associated with IM trough level was also investigated. The AA genotype in CYP2C19*2 (681G 〉 A) was significantly associated with higher IM trough level than dominant genotype (p=0.021), whereas transporter genes did not show any significant results. The CC genotype of ABCG2 (421C 〉 A) gene was related with CCyR (OR 3.47, 95% CI 1.09–11.05; p=0.030). In conclusion, the incidence of optimal responses in newly diagnosed CML patients who had been treated with standard dose of IM for 6 months was significantly higher in the patient group with trough plasma IM level of ≥1320 ng/ml than the group with 〈 1320 ng/ml, and the trough level of IM was influenced by CYP2C19 genotype. Checking trough plasma IM level together with cytogenetic and molecular data at milestone timing may guide the clinicians to adopt dose escalation or 2nd tyrosine kinase inhibitors in CML patients showing suboptimal response or resistance to standard dose of IM. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3381-3381
    Abstract: Abstract 3381 Poster Board III-269 This study compared the results of allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated and related donors, and involved 235 consecutive patients from 10 centers who received an allogeneic PBSCT for hematological malignancies between Jan 2004 and Dec 2008. Among these patients, 160 (68.1%) received an HLA-matched related PBSCT and 75 (31.9%) a matched unrelated PBSCT. Sixty-five patients (27.7%) had a high-risk disease status at transplantation. The cumulative incidence of acute graft-versus-host disease (GVHD) was 43.9% for the related PBSCT group and 59.3% for the unrelated PBSCT group (P-value:0.011). Although the cumulative incidence of chronic GVHD was no different between the related (54.2%) and unrelated (64.9%; P-value:0.199) PBSCT groups, the cumulative incidence of extensive chronic GVHD was higher among the unrelated PBSCT group (34.9%) than among the related PBSCT group (17.0%; P-value:0.015). Plus, the unrelated PBSCT group showed a higher cumulative incidence of CMV infection (44.6%) than the related PBSCT group (26.8%; P-value:0.002). The overall survival rate at four-year was 58.2% versus 49.1% (p=0.698) and the cumulative incidence of relapse 28.4% versus 25.0% (P-value:0.289) for the related and unrelated PBSCT groups, respectively. Among the factors examined, unrelated PBSCT (P-value:0.024), the CD34-positive cell count ( 〉 6 × 106/kg; P-value:0.041), and CMV infection (P-value:0.066) were all related with a higher incidence of extensive chronic GVHD. However, in a multivariate analysis, only unrelated PBSCT was identified as a risk factor for the development of extensive chronic GVHD (hazard ratio=2.012, 95% confidence interval=1.006-4.023; P-value:0.048). In conclusion, the overall survival and relapse incidence were not significantly different between the related and unrelated PBSCT groups. However, a higher incidence of CMV infection and extensive chronic GVHD was observed in the unrelated PBSCT group. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 3
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4615-4615
    Abstract: Introduction: The methylated proportion of the gene, turning on the cell cycle, increases with a progression of MDS. Newly introduced demethylaing agent, azacytidine (AZA) may be more active in advanced cases of MDS. Early data for the hematologic responses in several stages of MDS supported this. The powerful tool predicting the outcome of MDS is international prognostic scoring system (IPSS). Our study is to compare the response to AZA among the IPSS risk groups using international working group criteria. Methods: One hundres five patients with MDS were treated with AZA from May 2006 till August 2007. Seven patients had insufficient data. Finally, 108 patients were enrolled. Results: Their median age was 59 years-old (range; 20∼83), and male to female ratio was 2.09. The previous hematologic diseases documented in 8 patients; apalastic anemia (7), and megaloblstic anemia (1). The secondary MDS occurred in 3 patients; after the chemotherapy (2) and radiotherapy (1). A median time from the diagnosis to treatment was 3 months (0∼183). The previous treatment (percentage of patients given) was the transfusion of RBC (74%) and PLT (35%), oxymetholone (17%), steroid (13%), erythropoietin (7%), cyclosporine (7%), ATG (5%), valproic acid (5%), chemotherapy (3%), and allogeneic SCT (2%). Their ECOG performance scale was 0 (58 patients), 1 (45) and 2 (5), respectively. Their diagnoses just before the AZA were RA (20 patients), RARS (5), RCMD (27), RCMD-RS (6), RAEB-1 (27), RAEB-2 (20), MDS-U (1), MDS with isolated 5q− (1) and CMMoL (1). A number of patients with a LOW, INT-1, INT-2, and HIGH risk was 4 (4%). 70 (65%) 23 (21%) and 11 (10%), respectively. The rate of hematologic response (CR+PR+marrow CR+HI) and cytogenetic response (continued normal karyotype and CR) were similar; 100%/75%/93%/67% and 100%/59%/50%/50% in LOW/INT-1/INT-2/HIGH risk groups, respectively. There were 6 treat-related mortalities, and their causes of death were infection in 4 patients and bleeding in 2 patients. Two patients stopped after one cycle of treatment because of grade 4 hepatoxicity and pulmonary toxicity, respectively. During a median follow-up of 9 months, 4 patients were confirmed as transformation to AML and 1 patient suffered from persistent marrow aplasia. One-year expected overall and failure-free survival was 82 ± 5% and 79 ± 6%, respectively in 108 patients. Conclusion: AZA showed the equal activity in 4 risk groups on IPSS in patients with MDS. Not only the hematologic response but the cytogenetic response was similar between 4 groups.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 4
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 4559-4559
    Abstract: Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree of morphologic and clinical heterogeneity. Recently, Rosenwalt et al. (N Engl J Med 2002) reported that four gene expression “signature”, 17 genes were identified as correlated with patient outcome by DNA microarray in DLBCL. In this study, we aim to establish predictor of outcome could help to identify patients who may benefit from risk-adjusted therapies in advance. To do it, we evaluate the prognostic relevance of 17 gene expressions in 72 patients with DLBCL who received a conventional chemotherapy. Seventeen genes were studied using RT-PCR assay from paraffin-embedded sections at the time of diagnosis. The median age of the patients was 58 years (range: 21–80 years). When we initially exam an appropriative patient’s selection for survival analysis, overall survival (OS) at 2 years in patients with the international prognostic index (IPI) 〈 2 and IPI ≥ 2 were 95.2±4.6% and 50.6±11.8%, respectively (p = 0.009), and progression free survival (PFS) at 2 years in patients with the IPI 〈 2 and IPI ≥ 2 were 75.0±9.7% and 46.7±12.9%, respectively (p = 0.049). Of the 17 genes, patients with uPA expression showed a shorter OS compared with those without the gene expression. Additionally, patients with the expression of NPM3, uPA, fibronectin, or IMAGE814622 showed a shorter PFS compared with those without the gene expressions. In conclusion, these findings suggest that the gene expression profiling with simple RT-PCR assay is useful for analysis of the prognostic implications in patients with DLBCL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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