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  • Hatake, Kiyohiko  (8)
  • Inoue, Norihito  (8)
  • Yamauchi, Hirofumi  (8)
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  • 1
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5554-5554
    Abstract: Introduction: Myelodysplastic syndromes (MDS) are clonal hematopoietic neoplasms characterized by abnormal maturation of precursor cells which often translates into peripheral blood cytopenias and a high rate of transformation to acute myeloid leukemia (AML) due to accumulation of genetic alterations. The AZA-001 trial showed azacitidine (AZA) significantly prolonged median overall survival compared with conventional care regimens (24.5 vs 15.0 months; P=0.0001). AZA is standard first-line treatment for Intermediate-2 and High-risk myelodysplastic syndrome patients who are not immediate candidates for allogeneic stem cell transplantation, but this study included no cases of therapy related MDS (t-MDS). T-MDS is known to have poor prognosis, therefore it is very important to analyze the outcome of patients with t-MDS treated in the front-line with AZA. Methods: We studied newly diagnosed 29 MDS patients who were treated by AZA in our hospital from July, 2010 to April, 2016, retrospectively. AZA was given subcutaneously at 75 mg/㎡per day for 5 or 7 days every 28 days. Results: We analyzed 29 MDS patients. According to the WHO classification, there were 12 RA, 15 RCMD, 10 RAEB-1, 2 RAEB 2 and 1 MDS-U. The median age was 70 year (range 49-88), and men was 12 (41.3%). There were 12 de novoMDS cases (41.3%) and 17 t-MDS cases (58.6%). All of the t-MDS patients had previously received chemotherapy (17 patients, 100%) and 9 patients had also received radiotherapy (9 patients, 53%). Very poor risk group was 47.1% (9/17) in t-MDS group compared to 25.0% (3/12) in de novo MDS group (P=0.26). Median follow up time was 11.4 months (range 1.4-47.8). Twenty five patients (86.3%) were treated by AZA for 5 days. Four patients (13.7%) were treated by AZA for 7 days, but all 4 patients decreased the dosing period to 5 days due to unacceptable toxicity. AZA was given for a median of 4 cycles (range 1-33). In 29 MDS patients, 1-year overall survival (OS) was 60.5% (95% CI, 38.7-76.7%) and 1-year PFS was 40.1% (95% CI, 18.8-60.6%). After a median follow-up of 11.4 months, median OS was 18.7 months (95% CI, 9.4-21). One-year OS was 59.3% in t-MDS group compared to 63.6% in de novo MDS group (P=0.294). 1-year PFS was 38.4% in t-MDS group compared to 40.4% in de novo MDS group (P=0.626). One-year OS was 37.5% in very poor risk karyotype group (R-IPSS) compared to 74.6% in not very poor risk karyotype group (P=0.000748). 1-year PFS was 43.2% in very poor risk karyotype group compared to 39.0% in not very poor risk karyotype group (P=0.594). Focusing on t-MDS group, 1-year OS was 46.9% in very poor risk karyotype group (8/17 47%) compared to 74.1% in not very poor risk karyotype group (9/17 53%) (P=0.054). 1-year PFS was 48.0% in very poor risk karyotype group compared to 26.0% in not very poor risk karyotype group (P=0.339). Conclusions: In our study, 1-year OS in all MDS patients was 60.5%. It was slightly poor prognosis than 1-year OS in AZA-001 trial (about 70%). Our study include t-MDS cases (58.6%). Additionally, AZA was given for a median of 4 cycles in our study but 6 cycles in the AZA-001 trial. It showed severe patient's background of our study. These difference may cause the lower median OS and poorer prognosis. There trended to be more patients who had very poor risk karyotype in t-MDS group, but there was no significant difference between t-MDS and de novoMDS for the 1-year OS and PFS. Azacitidin is effective in the therapy related myelodysplastic syndrome. Disclosures Yokoyama: Chugai: Consultancy. Mishima:Chugai: Consultancy. Nishimura:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Kyowa Kirin: Honoraria, Research Funding; Chugai: Research Funding; Otsuka: Consultancy; Meiji-Seika: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 2
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4221-4221
    Abstract: Background: Introduction of Rituximab has shown a remarkable improvement on survival for the patients with diffuse Large B cell Lymphoma (DLBCL). However, involvement of central nervous system (CNS) at relapse in these patients is still an issue and a mostly fatal with a median survival of 2.5 - 4 months when they treated with conventional therapies. The Memorial Sloan - Kettering Cancer Center (MSKCC) prognostic score has been used as a statistically powerful model to patients with newly diagnosed primary central nervous system lymphoma (PCNSL) before rituximab introduction. By contrast, effective prognostic model for the relapsed DLBCL patients with CNS involvement in the rituximab era is unclear. The purpose of this study was to address treatment response and detailed prognosis of CNS recurrence of DLBCL after initial treatment with Rituximab contained chemotherapy. Patients and Methods: In total, 560 newly diagnosed de novo DLBCL patients treated with R- Results: Among the 25 patients assessed in this study, median age was 61 years (range, 34-81 years) at relapse.Sixteen (64%) patients were male. Primary sites at initial diagnosis were mostly extra-nodal sites such as nasal cavity, paranasal sinuses, skin, primary effusion, breasts, testes, ovaries, gastro-intestine, kidneys, adrenal glands, and bone in 88% (22/25) of the patients. The cell of origin of germinal center (GC) subtype by Hans algorithm were shown in 47.6% (10/25). All patients other than one with stage I were to receive 6 to 8 cycles of R-CHOP and the patient with stage I were to receive combined modality therapy with 3 cycles of R-CHOP followed by involved field radiation therapy as an initial treatment. Only two patients received intrathecal prophylaxis. The median interval between the initial diagnosis and CNS relapse was 22 months (range, 1-100 months). The patients status at relapse were 44% of (11/25) first complete response (CR), 32% of (8/25) first partial response (PR), 20% (5/25) of second CR, and 4% (1/25) of second PR after the latest chemotherapy. There were 15 patients (60%) with brain intra- parenchymal lesions identified by brain imaging and the others (40%) with leptomeningeal infiltration revealed with cerebrospinal fluid analysis. Front-line treatment for relapse at CNS lesion was chemotherapy with or without whole brain radiotherapy (WBRT) in 13 patients (52%). A total of 6 patients (24%) received WBRT without chemotherapy. The others received the best supportive care. In addition, most patients through those three groups received intrathecal chemotherapy with MTX, Ara-C, and prednisone. The median overall survival (OS) after CNS relapse was 7 months (95% CI: 5-12) for the whole population, 12 months for chemotherapy group, 6.5 months for WBRT group, and 2 months for BSC group (p = 0.02). To date 22 patients (88%) had died. At univariate analysis significant prognostic factors for overall survival were age at relapse (P=0.02), elevated b2- microglobulin (b2-MG) (p=0.03), and response for the latest chemotherapy (p=0.01) that was only a significant factor in multivariate analysis. Thus we established Relapsed-MSKCC prognostic score consisting of age 〈 50, KPS 〉 =70, and response for the latest chemotherapy; add 1 to MSKCC score if they did not achieve CR after the latest therapy. The median OS in patients with a R-MSKCC prognostic score of 1 was not reached, and differed significantly from the 13 months in patients with a R-MSKCC score of 2, 8 months in patients with a R-MSKCC score of 3, and 2 months in patients with a R-MSKCC score of 4 (P=0.01). Conclusions: The Survival of CNS recurrence in patients with DLBCL remains lethal. R-MSKCC prognostic score may predict survival better in these patients. Figure Figure. Disclosures Nishimura: Chugai pharmaceutical co.LTD: Consultancy. Terui:Yanssen: Honoraria. Mishima:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Hatake:Meiji-Seika: Consultancy; Kyowa Kirin: Honoraria, Research Funding; Otsuka: Consultancy; Chugai: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5360-5360
    Abstract: Introduction Extranodal NK/T cell lymphoma (ENKTL) is a rare aggressive lymphoma, and more prevalent in Asians, Mexico, Central America, and South America. ENKTL relates to Epstein-Barr Virus (EBV) reactivation, and occurs most often in adults. The prognosis of ENKTL relates to NK/T Cell Lymphoma Prognostic Index (NKPI), which includes presence of B symptom, elevated serum lactate dehydrogenase (LDH), stageⅢ or Ⅳ, and regional lymph node involvement. Recently, EBV-DNA level is known to be an important prognosis factor of ENKTL. We retrospectively analyzed relationship among NKPI, EBV-DNA level and other factors in patients with ENKTL. Patients and methods We analyzed the data of ENKTL patients who were diagnosed and treated at our hospital from April 2007 to July 2016, retrospectively. Data of the blood test and EBV-DNA level, when we diagnosed were also analyzed. PET-CT examination was performed for staging of ENKTL before treatment. The event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method. Results A total of 26 ENKTL patients (14 male, 12 female) were analyzed. All patients were treated with radiation therapy (RT) and 2/3DeVIC (dexamethasone 40mg/body days 1 through 3, ifosfamide 1000mg/m² days 1 through 3, carboplatin 200mg/m² day 1, etoposide 67mg/m² days 1 through 3). Median age was 58 years old (range; 18-77 years old). Median OS was 17 months (range; 1-105 months), and EFS was 12 months (range 1-105 months). Seven patients had B symptoms, and serum LDH level (median 192.5 U/L, range 153-540 U/L) was elevated in 10 patients at diagnosis. The patients with stage Ⅰ, Ⅱand Ⅳ were 19, 5, and 2 patients, respectively. The patients with stage Ⅳ were treated with RT and 2/3DeVIC, because patient's performance status, age or other factor is not good. According to the NKPI, the patients were stratified into low score (10 patients), low intermediate (13 patients), and high intermediate (3 patients). In our analysis, 2 year-EFS (p=0.125) was not changed among all score groups o However,, low score group was associated with better 2 year-OS (p=0.0734) than intermediate and high score groups. Twenty patients were tested EBV-DNA level at diagnosis. Median EBV-DNA at diagnosis was 113.5 copies/10⁶WBC (range; 0-38000 copies/10⁶WBC). We analyzed relationship between the prognosis and EBV-DNA level. However, EBV-DNA level (EBV-DNA cut-off; 140 copies/10⁶WBC ) was not related to 2 year-OS (p=0.838) and 2 year-EFS (p=0.686). Twenty-six patients were tested serumβ2-microglobulin (β2MG) and soluble IL-2 receptor (sIL2R). Serum β2MG level (median; 2.035 mg/l , range; 1.10-4.95 mg/l) was increased in 13 patients, and serum sIL2R level (median; 543 U/ml, range; 264-2490 U/ml) was increased in 14 patients. β2MG level was not related to 2 year-OS (p=0.152) and 2 year-EFS (p=0.181). Low sIL2R level was associated with better OS (p=0.0445) and EFS (p=0.0793) than high level. Discussion NKPI score and serum sIL2R were related to the prognosis of patients with ENKTL with early stage, although EBV-DNA copies were not related to the prognosis. Disclosures Nishimura: Chugai: Consultancy. Mishima:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Chugai: Research Funding; Meiji-Seika: Consultancy; Otsuka: Consultancy; Kyowa Kirin: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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    detail.hit.zdb_id: 80069-7
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  • 4
    In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 97, No. 2 ( 2018-2), p. 289-297
    Type of Medium: Online Resource
    ISSN: 0939-5555 , 1432-0584
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 1458429-3
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  • 5
    In: Annals of Oncology, Elsevier BV, Vol. 28 ( 2017-10), p. ix82-
    Type of Medium: Online Resource
    ISSN: 0923-7534
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2003498-2
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  • 6
    In: Annals of Oncology, Elsevier BV, Vol. 29 ( 2018-10), p. vii59-
    Type of Medium: Online Resource
    ISSN: 0923-7534
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2003498-2
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  • 7
    In: British Journal of Haematology, Wiley, Vol. 183, No. 4 ( 2018-11), p. 661-664
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1475751-5
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  • 8
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5682-5682
    Abstract: Introduction: Autologous stem cell transplantation (ASCT) is standard therapy for newly diagnosed multiple myeloma (NDMM) patients who are younger than 70 years old. In the IFM 90 trial, 5-year OS was 52% in the ASCT group compared to 12% in the initial chemotherapy group (p=0.03). 5-year EFS was 28% in the ASCT group compared to 10% in the chemotherapy only group (p=0.01). MRC Ⅳ trial also showed a higher rate of OS (p=0.04) and PFS (p 〈 0.001) in the ASCT group. However, there was no result about the differences of the prognosis between CR and PR before ASCT. In this study, we studied the response level before ASCT to understand if it is related to the prognosis after ASCT. Methods: We studied 25 NDMM patients who received ASCT in our hospital from 2005 to 2015. Induction therapies were VRD, VCD, VAD, VD, Rd or VTD-PACE. Stem cells were collected using G-CSF or cyclophosphamide plus G-CSF. After stem cell harvest, all patients underwent high dose melpharan (200mg/m2) before ASCT. The responses according to the IMWG guidelines were performed at the point of 4-6 weeks after ASCT. Statistical analyses were performed using a software, EZR version 1. Results: The total number of NDMM patients was 25. The median age was 55 years (range 33-62), the median follow-up period was 1,375 days (range 340-3,763). Male were 16 (64%), 11 patients (44%) were ISS Ⅱor more and 20 (80%) were D & S stageⅡor more. ECOG PS 2 was 4 patients (8%) and one (4%) is ECOG PS 3. Before ASCT, 21 patients (84%) received 1 regimen and 4 (16%) received 2 regimens. In the 1 regimen group, 9 patients (43%) were treated by VCD with 2-4 cycles, 9 received VD with 4-5 cycles and 5 (24%) were received VAD with 3 cycles before ASCT. In the 2 regimens group, details of induction therapy were VD with BCD, VCD with Rd, VCD with VRD and VCD with VTD-PACE. In all patients, 3-year OS was 91.6% (95% CI, 70-98%) and 3-year PFS was 56% (95% CI, 34-74%). After induction therapy, CR was achieved in 11 (44%), VGPR was 2 (8%), PR was 11 (44%) and MR was 1 (4%). After ASCT, CR was achieved in 18 (72%), VGPR was 2 (8%), PR was 4 (16%) and PD was 1 (4%). 4 patients (16%) died for progression of multiple myeloma. There were no statistical differences in 3-year OS and PFS between CR group and VGPR + PR group after induction therapy (3-year OS; 100% vs 92%, p=0.11, 3-year PFS; 70% vs 50%, p=0.26). There were also no differences between the two groups CR group and PR without VGPR group (3-year OS; 100% vs 90%, p=0.18a, 3-year PFS; 70% vs 60%, p=0.4). As sub-analysis, the achievement time until normalization of FLC and disappearance of serum or urine M-protein in IFE did not affect 3-year OS and PFS. Discussion and Conclusions: When MM patients having residual disease did the stem-cell harvest, it has been possible to contaminate of myeloma cells in their collected stem cells. Several literatures described the contamination of myeloma cells in the stem cells induced inferior prognosis after ASCT. However our limited data suggested that the prognosis of patients who had residual disease after induction therapy, if they had achieved better than PR, were not inferior to CR group. This is reasonable data for recommendation of ASCT to MM patients getting PR after induction therapy. Disclosures Mishima: Chugai: Consultancy. Nishimura:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Chugai: Research Funding; Otsuka: Consultancy; Kyowa Kirin: Honoraria, Research Funding; Meiji-Seika: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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