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  • American Society of Hematology  (25)
  • Lee, Won Sik  (25)
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  • American Society of Hematology  (25)
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  • 1
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 6719-6720
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 2
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1657-1657
    Abstract: Background Nodal peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of neoplasms, which include PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large-cell lymphoma-anaplastic lymphoma kinase positive (ALCL, ALK-pos), and ALCL, ALK-neg. International prognostic index (IPI) is a widely used tool for risk stratification and has shown a strong association with survival in nodal PTCL. The prognostic index for PTCL-U (PIT) is a specific prognostication tool for PTCL and has also shown prognostic relevance in nodal PTCL. The National Comprehensive Cancer Network-IPI (NCCN-IPI) has recently been reported to show better discrimination in higher risk patients with diffuse large B-cell lymphoma, but has never been investigated in nodal PTCLs. Thus, the aim of this study was to validate and compare the usefulness of risk stratification using NCCN-IPI in comparison with the IPI and PIT in patients with newly diagnosed nodal PTCL, particularly in determining high-risk patients. Methods This retrospective analysis was conducted using patient-level data from one Korean multicenter retrospective cohort (cohort A; NCT03040206; Eur J Nucl Med Mol Imaging 2018 e-pub) and two prospective Samsung Medical Center Lymphoma I (cohort B) and II (cohort C) cohorts (NCT00822731 and NCT01877109; Blood Cancer J 2016;6:e395) that included nodal PTCL patients. Among those enrolled in the three cohorts, patients were eligible if they were newly diagnosed, were histologically confirmed with nodal PTCL and had received curative intent systemic chemotherapy. Patients were excluded if the histologic subtype was uncertain or primary extranodal mature T-cell or NK/T-cell neoplasms. The study also excluded ALCL, ALK-pos. Results A total of 531 patients were screened for eligibility (A [n=396], B and C [n=135] ). Eighty-four patients were excluded from this analysis due to following reasons: relapsed nodal PTCL (n=14), no systemic lymphoma therapy (n=14), uncertain histology (n=8), primary extranodal mature T-cell or NK/T-cell neoplasms (n=9), and ALCL, ALK-pos (n=39). Thus, 447 patients were analyzed. Median age at diagnosis was 60 years (range, 19-86) and 285 (64%) were male. PTCL-NOS (n=237, 53%) was the most common histologic subtype included, and AITL (n=154, 35%) and ALCL, ALK-neg (n=56, 13%) followed. Three-fourths of the patients (n=337) were advanced stage and approximately one-fourth of the patients (n=127) had bone marrow involvement at diagnosis. The majority of the patients (n=422, 94%) were treated with anthracycline-based regimen as primary chemotherapy. 77 patients (17%) underwent up-front autologous stem cell transplantation. With a median follow-up of 55.7 months (IQR 32.7-83.5), 5-year progression-free survival rate was 35.9% (95% CI, 31.0-40.8) and overall survival (OS) rate was 46.0% (95% CI, 40.7-51.3). In the univariate analysis, all the risk stratifications, the IPI, PIT, and, NCCN-IPI, were significantly associated with OS (Fig 1A, B, C). However, the 5-yr OS rates of IPI, PIT, and NCCN-IPI differed substantially in the high-risk group,18.2% (95% CI, 9.6-26.8) vs 22.4% (95% CI, 14.0-30.8) vs 10.8% (95% CI, 2.4-19.2), as well as in the low-risk group, 77.1% (95% CI, 69.3-84.9) vs 75.9% (95% CI, 65.3-86.5) vs 85.8% (95% CI, 76.0-95.6; Table 1), respectively. The absolute difference in OS between the low-risk and high-risk groups was 75.0% with NCCN-IPI stratification compared with 58.9% and 53.5% with IPI and PIT stratifications. Notably, 13.4% of the patients were classified as high-risk group using the NCCN-IPI stratification, which was substantially different from stratifications using the IPI (19.2%) and PIT (24.2%). Finally, the NCCN-IPI and histologic subtypes were found to be independent prognostic variables for OS in multivariate analysis (for low-intermediate NCCN-IPI, hazard ratio [HR] 1.80, 95% CI 0.79-4.12; high-intermediate NCCN-IPI, HR 2.19, 95% CI 0.83-5.76; high NCCN-IPI HR 3.63, 95% CI 1.28-1032; P=0.038: for AITL, HR 1.12, 95% CI 0.69-2.01; PTCL-NOS, HR 1.96, 95% CI 1.18-3.27; P 〈 0.001). Conclusion Our study shows that the NCCN-IPI is a more powerful tool than the IPI and PIT for predicting OS in patients with nodal PTCLs. Compared with the IPI and PIT, the NCCN-IPI also shows better discrimination between low-risk and high-risk nodal PTCL patients, and may be more useful to find truly high-risk patients. 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: 2018
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  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4002-4002
    Abstract: Introduction In aggressive lymphoma, the prognostic value of FDG-PET/CT is well established to assess the response to therapy and predict long-term outcome. However, there are still many controversies for using PET/CT in indolent non-Hodgkin lymphomas because of the low FDG avidity. Therefore, this study was planned to evaluate the roles of PET/CT in marginal zone lymphoma, which is a representative of indolent lymphoma. Method We retrospectively analyzed the data of 136 patients with advanced stage marginal zone lymphoma from 13 independent institutions between January 2008 and January 2018. All of the enrolled patients had Ann Arbor stage III-IV except some patients with stage II with bulky mass or rapid progression. Patients were treated with 6th or 8th cycles of immunochemotherapy which consisted of R-CVP (Rituximab, cyclophosphamide, vincristine, prednisolone) (90.4%), R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (5.9%), R-B (Rituximab, bendamustine) (3.7%). PET/CT scan was performed at diagnosis, after 2~3 cycles of immunochemotherapy (interim), and at the end of the treatment. Interim PET/CT response was assessed according to Deauville 5-PS (DS) and semi-quantitative assessment based on the rate of reduction in the SUVmax (deltaSUVmax). Results The median age of the patients was 59.5 years (range;28.0~84.0), and 115 patients (84.6%) had stage III-IV. 119 patients (87.5%) had one or more extranodal site involvement, and gastrointestinal tract (25%) was the most commonly involved extranodal site. Fifty-one patients (37.5%) were classified into high risks and 85 patients (62.5%) were with low risks based on IPI. The median SUVmax of the lesion was 4.8 (range; 0.8-23.5) on initial PET/CT. According to Deauville 5-PS in interim PET/CT, 37 patients (27.2%) were defined in score 1, 34 patients (25.0%) in score 2, 31 (22.8%) patients in score 3, 27 patients (19.9%) in score 4, and 7 patients (5.1%) in score 5. The optimal cutoff value for the deltaSUVmax was 59.8 according to the ROC analysis. After median follow up of 35.9 months, performance status, LDH, IPI and interim PET/CT response were significant prognostic factors for progression free survival (PFS) in univariate analysis. Patients who achieved complete metabolic response (DS 1-2) showed significantly longer progression free survival (PFS) than patients with DS 3-5 grade (Figure 1A, 89.3 months vs. 43.9 months, P=0.046). However, the semi-quantitative method using deltaSUVmax did not predict the survival outcome. In regard to post-treatment PET/CT assessment, patients who achieved complete response showed long PFS (Figure 1B, P 〈 0.05). In multivariate analysis, complete metabolic response (DS 1-2) achievement in interim PET/CT was the strong prognostic factor in patients with advanced stage marginal zone lymphoma (HR 2.017, 95% CI 0.981-4.147, P 〈 0.05). Conclusion Deauville 5-PS based interim PET/CT response assessment is useful to predict the survival outcome of advanced stage marginal zone lymphoma in post-rituximab era. Whereas, the semi-quantitative assessment based on deltaSUVmax did not have the prognostic impact. Figure 1. Progression free survival of all patients according to Deauville 5-PS based interim PET/CT response (Figure A, B) and post-transplant PET/CT response (Figure C) Figure 1 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: 2019
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  • 4
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1802-1802
    Abstract: Systemic inflammatory factors such as C-reactive protein (CRP), ¥â2-microglobulin (B2MG), and ferritin were documented an prognostic factor in patients with hematologic malignancies including lymphoma. The purpose of this study was to find the significance of systemic inflammatory factors for predicting survival outcome in patients with diffuse large B cell lymphoma (DLBCL). Methods A total of 188 patients who newly diagnosed DLBCL and received an rituximab combined chemotherapy at the South Korea between September 2004 and April 2012 were enrolled retrospectively in the current study. Pretreatment serum CRP, B2MG, and ferritin were measured within 4 weeks before the beginning of first line chemotherapy. Results The median age of patients was 58 years (range, 14-84 years) and the mean level of serum CRP, B2MG, and ferritin at pre-treatment were 2.37 mg/dL (range: 0.01 – 29.80), 2.64 mg/L (range: 0.71 – 24.01), and 285.01 ng/ml (range: 5.34-4872.40). Systemic inflammatory factors score were given 1 point if serum levels were more than normal range (CRP; 0.8 mg/dL, B2MG; 2.5 mg/L and ferritin; 220 ng/ml). Systemic inflammatory risk were divided into three groups according to systemic inflammatory factors scores ; low risk was 0 score, intermediate risk was 1 or 2 score, and high risk was 3 score respectively. 5-year progression free survival rates (PFS) were 66.9%, 65.0% and 10.6% in risk groups respectively (p 〈 0.001). 5-year overall survival rates (OS) were 74.4%, 48.8% and 19.8% in risk groups respectively (p 〈 0.001). Conclusions Systemic inflammatory factor (CRP, B2MG and ferritin) score were associated with survival outcomes in patients with DLBCL treated by R-CHOP. However, further studies are needed to confirm prognostic value of systemic factors such as CRP, B2MG and ferritin. IPI, international prognostic index; LDH, lactate dehydrogenase; ECOG, Eastern Cooperative Oncology Group (ECOG) performance status; CRP, C-reactive protein; BM, bone marrow; ALC, absolute lymphocyte counts; CHOP-like (cyclophosphamide, adriamycin, vincristine, prednisolone); RCHOP (rituximab plus CHOP) Systemic inflammatory factor (normal range); ¥â2-microglobulin (2.5mg/L), CRP (0.8mg/dL), ferritin (220 ng/mL) Systemic inflammatory factor score : given 1 point if more than normal range Low risk ; 0, Intermediate risk ; 1 or 2, High risk ; 3 Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 5
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1811-1811
    Abstract: BACKGROUND: According to our prior prospective phase II trial, Rituximab in combination with chemotherapy (R-CVP) has been shown to improve response rate (RR) and progression free survival (PFS) in patients with advanced stage marginal zone lymphoma (MZL) compared with chemotherapy alone (CVP). In spite of better RR and PFS, relapses seem to continue after immunotherapeutic treatment in these patients. Thus, eventual relapse remains an important clinical issue for the majority of patients with indolent lymphoma, and defining further ways to extend the period of remission remains an essential goal. But data from clinical trials evaluating rituximab maintenance treatment in these patients are almost limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the PFS of patients with MZL. METHODS: Histologically confirmed advanced stage MZL patients who did not progress at the end of 6~8 cycles of 1st line Rituximab-CVP (cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 (maximum 2.0 mg), given intravenously on day 1, and oral prednisolone 100 mg on days 1-5) regimen were enrolled. Patients received 2 years of rituximab maintenance therapy (375 mg/m2 every 8 weeks). Primary objection was three year progression free survival. This trial is registered with ClinicalTrials.gov, number NCT012113095. RESULTS Between March 2010 and March 2013, a total of 47 patients were enrolled with informed consent at this trial from 17 institutes in Korea. Among these patients, 1 patient withdrew informed consent, 1 patient was screening failure with combined thyroid cancer. The median age of the evaluated 45 (32 males, 13 females) patients is 54 (range 33-77) years. Fifteen patients (33.3%) evidenced nodal MZL, 30 (66.7%) extranodal MZL (10 patients were lung, 6 ocular, and 5 stomach, in order of frequency). The IPI score were 1 in 13 (28.9%), 2 in 21 (46.7%), 3 in 9 (20%), and 4 in 2 (4.4%) patients. The patients received a total of 6 or 8 cycles of 1st line R-CVP chemotherapy were 10 (22.2%) and 35 (77.8%), respectively. There were 20 CR (44.4%), 22 PR (48.9%), and 3 SD (6.7%). Median treated number of rituximab maintenance followed by R-CVP was 12 (range 1-12). Thirty two patients (71.1%) patients completed planned 12 cycles of rituximab maintenance. Disease progression during rituximab maintenance was 8 patients, 2 patients stopped treatment because of side effects (1 abdominal pain, 1 recurrent pneumonia) 2 patients were follow-up loss. Four patients were expired (each 1 pneumonitis, pneumonia, sepsis, and disease progression). PFS and OS rate at 3 years were 78.9% and 90.6%, respectively. CONCLUSION: 2 years of rituximab maintenance therapy after R-CVP first-line chemotherapy for advanced stage MZL might be improve PFS with tolerable toxicities Disclosures Kim: Celltrion, Inc.: Consultancy, Honoraria. Lee:Amgen: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 6
    In: Blood, American Society of Hematology, Vol. 126, No. 6 ( 2015-08-06), p. 746-756
    Abstract: Nilotinib plus multiagent chemotherapy was feasible and showed a comparable outcome to previous results with imatinib for Ph-pos ALL. The achievement of deep MR with nilotinib at postremission correlated well with the clinical outcomes for Ph-pos ALL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3654-3654
    Abstract: Introduction: The effect of imatinib plus combination chemotherapy were assessed in 87 patients, aged 16-71 years, with newly diagnosed Philadelphia Chromosome-Positive (Ph+) acute lymphoblastic leukemia (ALL). Methods: Imatinib (600 mg/day orally) was administered continuously with combination chemotherapy, starting from eighth day of remission induction treatment, then through 5 courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Molecular response monitoring was performed at the central lab (Asan Medical Center) with quantitative RT-PCR assays for peripheral blood or bone marrow BCR-ABL RNA in serial; at the time of diagnosis, at hematologic complete remission (HCR), and every 3 months thereafter. The molecular response was defined as complete (MCR) if the BCR-ABL/G6PDH ratio was less than 1x10-5. Results: Between October 2005 and February 2009, total 89 patients with newly diagnosed Ph+ALL were enrolled. With median follow-up of 5 years among survivors (range: 2.6-8.9 years) and data were frozen up in July, 2014. Two patients were not assessed, one due to a final diagnosis of CML blastic phase and one for refusal of the protocol treatment 4 months after enrollment. Eighty-two patients (94%) achieved HCR at a median 25 days (range, 14-69 days). Among these 82 HCR patients, 40 experienced recurrence of leukemia and 5-year relapse free survival (RFS) rate was 36.8%. Median time of RFS was 33 months (95% CI 20-46 months). In all, 24 patients died without leukemia progression or recurrence. Causes of treatment related morality were infection (n=5), bleeding (n=2), and HCT related complication (n=17). The 5-year overall survival (OS) rate was 33.4% and the median time of OS was 22.9 months (95% CI, 7.95-37.97 months). In total, 56 patients (68%) underwent allogeneic HCT in first HCR and had received a median 2 courses (range, 0-5 courses) of consolidation prior to HCT. At a median follow-up of 5-years (range, 2.1-8.4 years) after HCT, 23 patients experienced leukemia recurrence (cumulative incidence, 59.1%; 95% CI, 49.7%-68.5%). Of these 23 patients, 17 showed new molecular evidence of disease recurrence before hematologic relapse. Six patients, however, experienced hematologic recurrence without preceding molecular evidence of leukemia recurrence. The 5-year OS rate of patient underwent allogeneic HCT at first HCR was 52.6% and the median time of OS was 72.0 months (95% CI, 17.49-126.50 months). In the patients who completed the five cycles of consolidation, 7 patients were maintained on imatinib. Among these 7 patients, four patients finished 2-year imatinib maintenance. At median follow-up of 4 years (range, 1.9-7.4 years) after maintenance, 6 patients relapsed. The median time of RFS of patient who received maintain therapy was 40.7 months (95% CI, 24.38-57.19 months). One patient with relapse received HCT at second HCR after salvage therapy and two patients died with leukemia recurrence. Cumulative MCR rate was 88.5%, and median time to MCR was 54 days (range, 13-384 days). Median time of MCR duration was 13 months (range, 0.9-60.3 months). MCR achievement within 3months after remission induction was significant predictor of RFS (P=0.004) and OS (P=0.003). Thirty two patients who lost of MCR had significantly inferior RFS (P 〈 0.0001) and OS (P=0.001) then 41 who maintained MCR. Total mean imatinib dose intensity over the entire treatment period was 80% (range, 22-110%) and mean imatinib dose intensity during remission induction was 85% (range, 22-131%). Imatinib dose intensity during remission induction; 〉 90% vs. ¡Â90%; was significantly associated with median HCR duration (44 vs. 13 months, P=0.001, Fig. 1), median overall survival (39 vs. 10 months, P 〈 0.0001, Fig. 2), and 3-year MCR rate (61% vs. 19%, P=0.001, Fig. 3). The probability for maintaining MCR at 3 years according to total imatinib dose intensity; 〉 80% vs. ¡Â80%; was 57% (95% CI, 43.0-75.5%) and 33% (95% CI, 12.3-55.4%), respectively (P=0.05). Conclusions: The higher imatinib dose intensity is correlated with the better molecular response and the superior overall outcome. The quantitative monitoring of BCR-ABL transcript levels is useful in identifying subgroups of Ph+ALL patients at a high risk of relapse. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. 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: 2014
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4499-4499
    Abstract: Abstract 4499 Background: CD34+ cell dose has been the most reliable measure for predicting the kinetics of hematopoietic reconstitution including rapid neutrophil and platelet engraftment in allogenic stem cell transplantation (AlloSCT). Moreover, cell phenotypes related with engraftment were reported that CD34+CD33- cells and CD34+CD41+ cells, CD26, and CD8+ cytotoxic T cells and CD56+ natural killer cells, were potential predictors of early engraftment in HCT. The purpose of our study is to investigate predictors which influence on early engraftment including cell phenotypes and clinical factors in patients with hematologic malignancy underwent AlloSCT in South Korea. Methods: Three hundred twenty four patients who received AlloSCT from at hematopoietic stem cell transplantation centers in South Korea between September 1998 and November 2011 were analyzed in this study. Subset analyses of the peripheral blood stem cells (PBSCs) and peripheral lymphocytes were conducted by using a flow-cytometric method. Two-color (FITC; PE) flow-cytometric immunophenotyping was performed. The hematopoietic stem cell (CD34+ cells), T cells (CD3+), helper T cells (CD3+/CD4+), cytotoxic T cells (CD3+/CD8+), and NK cells (CD56+) were all analyzed on a FACScan. And other clinical factors were analyzed in this study such as age, sex, disease status before AlloSCT, cormobidity index score, intensity of conditioning regimen, donor age, donor sex, and etc. The definitions of engraftment were more than 0.5×109/L and 20 ×109/L after AlloSCT in neutrophil and platelet, respectively. Results: In univariate analysis, predictive factors for engraftment of neutrophil at least day 12 were shown complete remission (CR) state befo re AlloSCT (p-value; 0.002), donor age less than 30 years old (0.004), mononuclear cell counts (MNC) more than 7.0 × 108/kg (p-value; 0.001), CD34+ cells more than 5.0 × 106/kg (p-value; 0.045), CD3+ T cells more than 3.0 × 108/kg (p-value; 0.002) and CD3+/CD8+ T cells more than 2.0 × 108/kg (p-value; 0.012). Predictive factors for engraftment of platelet at least day 14 were female (p-value; 0.004), shown complete remission (CR) state before AlloSCT (p-value; 〈 0.001), donor age less than 30 years old (0.006), mononuclear cell counts (MNC) more than 7.0 × 108/kg (p-value; 〈 0.001), CD34+ cells more than 5.0 × 106/kg (p-value; 0.050), CD3+ T cells more than 3.0 × 108/kg (p-value; 〈 0.001), CD3+/CD4+ T cells more than 3.0 × 108/kg (p-value; 〈 0.001), CD3+/CD8+ T cells more than 2.0 × 108/kg (p-value; 〈 0.001) and CD56+ NK cells (p-value; 0.001). In multivariate analysis, significant predictive factors for engraftment of neutrophil on day 12 was CR state before AlloSCT (RR; 0.466, 95% C.I.; 0.263 – 0.824, p-value; 0.009) and for engraftment of platelet on day 14 were female (RR; 2.230, 95% C.I.; 1.079 – 4.608, p-value; 0.030), CR state before AlloSCT (RR; 0.332, 95% C.I.; 0.165 – 0.669, p-value; 0.002), CD3+ T cells more than 3.0 × 108/kg (RR; 3.649, 95% C.I.; 1.659 – 8.030, p-value; 0.001), and CD3+/CD8+ T cells more than 2.0 × 108/kg (RR; 2.505, 95% C.I.; 1.123 – 5.587, p-value; 0.025). Conclusion: In our study, predictive factors for engrafment of neutrophil at least day 12 was CR state before AlloSCT and engraftment of platelet at least day 14 were female, CR state before AlloSCT, CD3+ T cells more than 3.0 × 108/kg and CD3+/CD8+ T cells more than 2.0 × 108/kg. However, further studies are needed to determine more impressive predictive cell phenotypes and clinical factors for engraftment of neutrophil and platelet after allogenic stem cell transplantation. 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: 2012
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  • 9
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 55-55
    Abstract: We previously reported the interim analysis on the clinical outcome of nilotinib (Tasigna®, Novartis Pharma, Basel, Switzerland), when combined with multi-agent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) in adults. Herein, we reported the final results of the multicenter prospective phase2 trial of Adult Acute Lymphoblastic Leukemia Working Party, the Korean Society of Hematology. Newly diagnosed Ph+ALL patients aged 18 years old or more were eligible when they had adequate organ function. Diagnosis of Ph+ALL was performed via confirmation of the presence of Ph chromosome by conventional GTL-band technique, and/or positive molecular analysis with nested RT PCR for detection of BCR-ABL fusion transcripts. Written informed consent was obtained from all subjects. All patients received induction treatment consisting of vincristine, daunorubicin, oral or parenteral prednisolone, and nilotinib. After achieving complete remission (CR), subjects received either 5 courses of consolidation followed by 2-year maintenance with nilotinib, or allogeneic hematopoietic cell transplantation (alloHCT) depending on the donor availability, his/her tolerability, and patient’s wish. Nilotinib was administered twice a day with a single dose of 400mg (800mg per day) from day8 of induction until the initiation of conditioning for alloHCT or the end of maintenance therapy. Minimal residual disease (MRD) monitoring was performed at the central lab with quantitative RT-PCR assays for peripheral blood BCR-ABL RNA using LightCycler® Technology in serial; at the time of diagnosis, at hematologic CR(HCR), and every 3 months thereafter. BCR-ABL quantification was expressed relative to the amount of glucose-6-phosphate dehydrogenase (G6PDH) mRNA. The molecular response was defined as complete (MCR, MRD-negative) if the BCR-ABL/G6PDH ratio was less than 1x10-6. Toxicity was graded according to National Cancer Institute Common Toxicity Criteria (version 2.0). Subjects had been followed up for 2 years after alloHCT or during maintenance therapy. Data were frozen up in June, 2013. A total of 91 subjects (male: female = 45: 46) were enrolled onto the study between January 2009 and May 2012. The median age was 47 (range 18-71) years old. Type of BCR breakpoint was minor (e1a2) in 71% of patients. The median BCR-ABL/G6PDH ratio was 6.09 (bone marrow) and 3.28 (peripheral blood) at diagnosis. During induction, all subjects required blood product transfusion, and incidence of nonhematologic adverse events (AE) over grade 3 was 17% (jaundice), 18% (ALT elevation), 13% (lipase elevation), and 2% (pancreatitis). Neither QTc prolongation over 500ms nor significant arrhythmia happened among any subject and any cycle. HCR rate was 90% and median time to HCR was 27 days (range, 13-72); most of failure was due to death in aplasia (n=8). MCR rate at HCR was 55%, Cumulative MCR rate was 84%, and median time to MCR was 1.1 months (range, 0.6-15.8). Most common cause of dropout from study was treatment-related death (n=22; during induction/consolidation vs. after alloHCT = 12 vs. 10), and HREL (n=15). Nilotinib was interrupted 75 times among 64 subjects, reduced 14 times among 12 subjects, and discontinued permanently due to hematologic relapse (HREL, n=14), AE (n=6, over gr3:3), and other cause (n=2). Fifty nine patients underwent alloHCT, 34 with myeloablative and 25 with reduced-intensity conditioning. Incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were 41% and 29%, respectively. With a median follow-up of 20.7 months of surviving subjects, estimated hematologic relapse-free survival (RFS), and overall survival (OS) rate at 2 years were 74% and 70%, respectively. Among subject achieving MCR, 2-year molecular RFS rate was 56%. When events were defined as ‘dropout due to AE, isolated molecular / extramedullary relapse, HREL, and death from any cause’, median event-free survival was 12.5 months. In this prospective study, nilotinib was shown to be effective for adult Ph+ALL, and concurrent administration of nilotinib with cytotoxic drug was well-tolerable, although death in aplasia during induction was the most common cause of failure of achieving HCR. In terms of MRD, potential of nilotinib to achieve and maintain MRD negativity were satisfactory (Clinicaltrials.gov NCT00844298). Disclosures: Off Label Use: Nilotinib for Ph+ALL-sientific and academic purpose.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3255-3255
    Abstract: Background Supportive care (BSC) including hematopoietic cytokines still remains an important component of treatment for lower-risk myelodysplastic syndrome (LR-MDS) including low or intermediate-1 risk by International Prognostic Scoring System (IPSS) even in the era of hypomethylating agents (HMA). The role of front-line HMA for LR-MDS has not been clearly defined yet. In the current study, we evaluated the long-term outcomes of patients with LR-MDS treated with front-line HMA compared to those treated with supportive care. Methods The data of 353 patients diagnosed with LR-MDS from Oct 1992 to Jul 2013 were retrospectively evaluated. The prognostic factors affecting overall survival were evaluated within all population. Then, we performed a case-constrol study using 122 patients with propensity score matched (PSM) population. Results Initial patient population (n=353) included 110 patients treated with BSC and 243 treated with HMA. Patients characteristics (age, gender, IPSS risk groups, IPSS blast score, IPSS cytopenia score) were similar between two groups, however, ECOG performance status (PS) and IPSS cytogenetic score were biased between two groups. ECOG-PS 2-3 were 32 patients (29.1%) in BSC and 20 (9.3%) in HMA group (p 〈 0.001) and IPSS cytogenetic score °Ã0.5 were 27 patients (25.2%) and 33 (14.6%) in HMA group (p=0.032). In the multivariate analysis, ECOG-PS 2-3 (HR 4.586, p 〈 0.001), IPSS blast °Ã0.5% (HR 2.549, p 〈 0.001) and front-line HMA therapy (HR 2.019, p=0.006) were unfavorable factors affecting OS. Using PSM population, we performed a case-control study comparing the outcomes of 61 patients in each group who treated with BSC and front-line HMA. Patient characteristics were well balanced between two group. In the multivariate analysis, ECOG-PS 2-3 (HR5.036, p 〈 0.001), IPSS blast °Ã0.5% (HR 2.157, p=0.035), and first-line HMA therapy (HR 2.213, p=0.026) were still unfavorable factors for OS. The 5-year OS rate was 62.5±10.8% in BSC group and 41.0±7.4 in HMA group, respectively (p=0.049). Conclusion Front-line HMA for patient with LR-MDS showed inferior long-term outcomes compared to BSC in PSM population. The role of front-line HMA should be elucidated in prospective studies on LR-MDS patients. Figure. Overall survival between BSC and HMA groups in propensity score matched population Figure. Overall survival between BSC and HMA groups in propensity score matched population Disclosures Off Label Use: Rituximab has been used as an off-label drug for adult ALL, and has been provided by Roche Inc. for scientific purpose. .
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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