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  • 1
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4421-4421
    Abstract: Introduction Although several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT). Methods A prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky ( 〈 10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate. Results A total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p 〈 0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1). Conclusion In our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial. Table 1. Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Total (%) R-CHOP alone group (%) R-CHOP plus RT group (%) P -value Number of patients 357 (100) 299 (83.5) 58 (16.2) Treatment response Complete response 345 (96.6) 292 (97.7) 53 (91.4) 0.030 Overall response 351 (98.3) 294 (98.3) 57 (98.3) 1.000 Rate of relapse 35 (9.8%) 14 (7.4) 11 (22.4) 〈 0.001 Median time to relapse (95% CI) 11 (7-15) 11 (8-14) 10 (5-14) 0.346 Pattern of relapse 〈 0.001 (0.062) Locoregional 14 (4.7) (63.6) 4 (6.9) (30.8) Distant 8 (2.7) (36.4) 9 (15.5) (69.2) Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 2 Figure 2. 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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  • 2
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-22)
    Abstract: Upfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL. Methods We conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles. Results Patients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS. Discussion In summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 3
    In: Oncotarget, Impact Journals, LLC, Vol. 7, No. 44 ( 2016-11-01), p. 72033-72043
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2016
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  • 4
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 54 ( 2017-11-03), p. 92171-92182
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
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  • 5
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5535-5535
    Abstract: Background: To explore a real incidence of dasatinib-induced pulmonary arterial hypertension (D-PAH) in clinical practice, we investigated 82 imatinib or other 2G tyrosine kinase inhibitor (TKI)-failed chronic myeloid leukemia (CML) patients who received dasatinib as a second-line therapy. Methods: Routine chest X-ray and Doppler echocardiography were regularly evaluated in all patients and additional tests were performed if dyspnea developed on treatment. Results: Median age at the time of starting dasatinib was 48 (16-82) years. Of 82 patients, 8 patients (9.8%) showed an elevation of right ventricular systolic pressure (RVSP 〉 35mmHg) by Doppler echocardiography. Among them, 7 patients (8.5%) were considered D-PAH with a median dasatinib treatment duration of 32.6 (10.3-108.7) months. They underwent follow-up Doppler echocardiography median 5 (2-9) times. Five patients showed severe D-PAH (RVSP 〉 70mmHg), 1 was moderate (RVSP 46mmHg), and 1 was mild (RVSP 41mmHg). Advanced studies such as pulmonary angiographic catheterization (patient 1 and 2) or pulmonary arterial computed tomography (patient 3 and 4) were performed for confirming D-PAH or ruling out PAH due to pulmonary vascular abnormality. Six patients had bilateral pleural effusion and 1 had unilateral pleural effusion. With sildenafil (n=5) + dose reduction (n=1) + switch to other TKI (n=6), all of patients improved dyspnea, and RVSP level was completely resolved in 3 patients. In addition, previous nilotinib therapy and concomitant pleural effusion were significant contributing factors for D-PAH. Conclusion: Regardless of complete resolution of pleural effusion, a patient with sustained dyspnea on dasatinib treatment should be carefully evaluated by Doppler echocardiography and a regular monitoring will be needed for early intervention. Abstract 5535. Table 1. Characteristics of patients with dasatinib-induced PAH Cohort Age at PAH diagnosis (year) Sex Treatment duration before dasatinib (month) Previous therapy for CML Duration between initiation of dasatinib and diagnosis of PAH (month) Daily mean dose of dasatinib (mg/d) Duration between diagnosis of D-PAH and last follow up (month) Treatment of D-PAH Switch to other TKI Outcome 1 53 M 54.4 Interferon, Hydroxyurea, Imatinib, nilotinib 26.4 123 73.5 Sildenafil nilotinib and ponatinib partial 2 50 M 36.6 Interferon, Hydroxyurea, Imatinib, dasatinib, nilotinib 50.3 112 55.2 Sildenafil nilotinib and radotinib partial 3 37 F 31.7 Imatinib, nilotinib 21.7 88 39.7 SildenafilDose de-escalation radotinib partial 4 45 M 70.9 Hydroxyurea, Imatinib 69.8 101 35.2 SildenafilDose de-escalation ponatinib complete 5 59 F 107.4 Interferon, Hydroxyurea, Imatinib 83.6 92 14.3 none radotinib partial 6 46 F 12.6 Imatinib 29.1 76 13.0 Steroid, Sildenafil radotinib complete 7 38 F 30.2 Imatinib 33.1 98 10.2 Dose reduction NA complete 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: 2014
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  • 6
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 11, No. 3 ( 2011-06), p. 273-279
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
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    detail.hit.zdb_id: 2193618-3
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  • 7
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3936-3936
    Abstract: Recently, we have reported on two different types of EPCs from human umbilical cord blood(ASH 2005, Abstract #1706). These EPCs had different biologic properties in angiogenic capabilities during the HCB ex vivo expansion. In this present study, the aim is to examine the synergism by mixing the conditioned medium from the early EPCs into the late EPCs on neovascularization. The mononuclear cells from the HCB were cultures using an EGM-2 medium with VEGF, IGF-1 and FGF for 21 days. We found early spindle-shaped cells(early EPCs), which were grown in the first week of the culture and late cobblestone shaped cells(late EPCs) which peaked in their growth in the third week of the culture. First, we compared the two types of cells in terms of phenotypic expressions and migration ability. Next, we examined their proliferation capacity and tube formations in the Matrigel plate under the conditions that the early outgrowing cells-contained medium was added to the cobblestone shaped cells. The late-appearing cobblestone shaped cells were positive for VEGFR2, VE-cadherin, CD31, CD34 and CXCR-4 but not for CD14 and CD54. These late outgrowing cells expressed high levels of mRNA on the endothelial marker genes and effectively formed capillary tubes in the Matrigel plates. The early spindle cells excreted more angiogenic cytokines and had more migratory ability. When the early spindle-shaped cell-conditioned medium was added to the late cobblestone shaped outgrowing cells, significantly higher proliferation and tube formation measured by the area and length of tubes were found. These results suggested that the two types of cells raised with different biologic properties during the ex vivo HCB expansion and the angiogenic capacity of late EPCs were augmented by a mutual interaction via the excreted cytokines from early EPCs. These finding may have potential applications for a “cell therapy” in situations such as vascular injuries (ie, hindlimb ischemia/myocardial infarction). Murine models are being tested to see whether the injections of two different EPCs will result in synergic noevascularization in our Lab.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5216-5216
    Abstract: Though we were able to shorten the CD34+ cell mobilization by 24~48h by using continuous intravenous rhG-CSF rather than SQ rhG-CSF, it still will take several days when used normal individuals (Lee et al, BMT2005, 36:1027–1031). Previously we had reported that LT(Leukotriene)B4 was able to mobilize HSC in the murine model within 4 hours without significant side effects(ASH 2005). However, because there are possibilities of similar mechanisms during the HSC mobilization, which are shared by rhG-CSF or LTB4, in this study, we investigated the role of LTB4 receptors by rhG-CSF during HSC mobilization. LTB4APA and U75302, which are LTB4 receptor antagonists were given to C57BL/6 mice at different dose levels(0.5μg, 1μg, 2μg or PBS with equal volume in control arm) followed by rhG-CSF(5μg, IV) 2 hours later. 24 hours after the rhG-CSF injection, peripheral blood samples were obtained via cardiac puncture. The samples were analyzed for TNC using a trypan blue stain and FACS analysis were performed using Sca-1, Lin, CD45R(B220), CD116, Gr-1, TER119. The number of WBC and HSC were decreased in the rhG-CSF mobilized mice, in which LTB4 receptor antagonists were given. In those with up to 1μg of LTB4APA or U75302, there were tendencies of the blocking of the mobilization in the dose dependent manner. However, beyond 1μg of LTB4 receptor antagonists, the blocking effects plateaued. Interestingly, the blocking effects on mobilization by LTB4 receptor antagonists were more dramatic by the rh-GCSF than by the LTB4. Through our data, one can conclude that the LTB4 receptor is involved not only in the downstream pathway of rh-GCSF mobilization, but in the LTB4 mobilization pathway in C57BL/6 mice. Currently, hematopoietic stem cells mobilization is being tested to see the effects of rh-GCSF on LTB4 K/O mice. It is necessary to have insight into understandings more precise mechanisms on rhG-CSF and LTB4 mobilization for developing efficient protocols in the clinic.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 9
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4837-4837
    Abstract: Abstract 4837 Introduction The International Prognostic Scoring System (IPSS) or the WHO Classification-Based Prognostic Scoring System (WPSS) are considered as gold standard to evaluate the patients with MDS in terms of their clinical courses. Recently, a new prognostic cytogenetic risk classification, defined as favorable (5q-, 12p-, 20q-, +21, -Y, 11q-, t(11)(q23), normal, 2 abnormalities including 5q-), intermediate-1 (+1q, 3q21/q26-abnormalities, +8, t(7q), +19, -21, any other single, any other double), intermediate-2 (-X, -7/7q-, 2 abnormalities incl. -7/7q-, complex = 3 abnormalities) or unfavorable risk group (Complex 〉 3 abnormalities), has been reported through 3 large, well-characterized international investigations (German-Austrian (GA), Spanish MDS-registry, IMRAW). This new cytogenetic classification system showed better discrimination of patients according to their prognosis with respect to overall survival and leukemic transformation. The current study attempted to evaluate the new prognostic cytogenetic risk classification in patients with MDS, retrospectively. Patients and methods Between 1996 and 2007, 180 patients with MDS, who were diagnosed and treated at the Samsung medical center, Seoul, Korea, were enrolled into the study. One hundred seventy one patients were analyzed, 115 patients receiving best supportive care were included in the present analysis. Clinical characteristics were as follows; age 59 years (median, range 16-83), male 72%; 3 patients (pts) has 5q-; 1 patient (pt), 12p-; 3 pts, 20q-; 5 pts, -Y; 1 pt, 11q-; 1 pt, t(11)(q23); 80 pts, normal; 2 pts, 2 abnormalities including 5q-; 1 pt, +1q; 1 pt, 3q21/q26-abnormalities; 18 pt, +8; 16 pts, any other single; 19 pts, any other double; 2 pts, -7/7q-; 6 pts, complex = 3 abnormalities; 12 pts, complex 〉 3 abnormalities. Results According to IPSS, 10 patients (9%) were at low risk, 77 patients (67%) at intermediate-1 (Int-1) risk, 22 patients (19%) at intermediate-2 (Int-2) risk and 6 patients (5%) at high risk. According to WPSS, 10 patients (9%) were at very low, 25 patients (22%) at low, 36 patients (31%) at intermediate, 31 patients(27%) at high and 13 patients(11%) at very high risk group. According to new cytogenetic risk classification, 66 patients (57%) were at favorable, 34 patients (30%) at intermediate-1 (Int-1), 9 patients (8%) at intermediate-2 (Int-2) and 6 patients (5%) at unfavorable subgroup. The median OS in overall population was 23.2 months. According to the IPSS, median OS in the Low, Int-1, Int-2 and High subgroup was 37.8, 27.5, 14.8 and 11.6 months, respectively (p 〈 0.001). According to the WPSS, median OS in the subgroup of Very low, Low, Intermediate, High and Very high risk was 54.6, 43.1, 27.5, 16.5 and 11.9 months, respectively (p 〈 0.001). By the new cytogenetic risk classification, median OS in the Favorable, Int-1, Int-2 and Unfavorable subgroup was 23.8, 24.1, 13.0 and 9.1 months (p=0.035). Sixteen cases (13.9%) showed documented leukemic evolutions with median 9.2 months of onset. It was difficult to analyze of leukemic evolution risk due to small number of sample size. Discussion In the present study, the new cytogenetic risk classification does not seem to be validated retrospective series of patients, we couldn't validate that the new cytogenetic subgroups are powerful predictor of prognosis as good as IPSS or WPSS. To warrant availability of the new cytogenetic risk classification, large data sets should be necessary. Also, we should be consider review about the prognostic impact of the karyotype in MDS. 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: 2009
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  • 10
    In: Oncology, S. Karger AG, Vol. 81, No. 1 ( 2011), p. 55-62
    Abstract: 〈 i 〉 Objectives: 〈 /i 〉 We evaluated whether skin changes and soft tissue infiltration patterns reflect breast cancer subtypes based on the breast hormonal receptor (HR) and human epidermal growth factor receptor 2 (HER2) status at the time of skin metastasis. 〈 i 〉 Methods: 〈 /i 〉 We retrospectively reviewed the patients’ medical records with radiologic imaging studies. 〈 i 〉 Results: 〈 /i 〉 The numbers of patients of each subtype were as follows: HR positive (HR+ve) 53 (42.4%), HER2 enriched 43 (34.4%), and triple negative (TN) 29 (23.2%). The presence of skin ulceration was found more commonly in the HR+ve group than in the others (57.1% for HR+ve vs. 25% for HER2 enriched vs. 15.4% for TN, p = 0.019). Erythematous infiltrations were shown predominantly in the TN group (19.0 vs. 54.2 vs. 84.6%, respectively, p 〈 0.000). On CT scans, soft tissue infiltration appeared to be more common in the HER2-enriched and TN groups than in the HR+ve group (24.5 vs. 41.9 vs. 48.3%, respectively, p = 0.013). Erythematous infiltrative lesions were more common in patients with epidermal growth factor receptor overexpression (p = 0.036). 〈 i 〉 Conclusion: 〈 /i 〉 The patterns of skin involvement including surrounding soft tissue infiltration may reflect breast cancer subtype. Prospective evaluation is necessary to confirm their influential effect on breast cancer subtypes.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
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    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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