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Okazaki, Japan

Iwase H.,Nagoya Medical Center | Shimada M.,Nagoya Medical Center | Tsuzuki T.,Nagoya Medical Center | Ina K.,Nagoya Memorial Hospital | And 5 more authors.
Oncology | Year: 2011

Objectives: To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer. Methods: A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m2) was administered by infusion for 3 h on the first day. S-1 (70 mg/m2/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m2) was administered intravenously over 24 h on day 14 of every 28-day cycle. Results: All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months. Conclusions: Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer. © 2011 S. Karger AG, Basel. Source


Nishiwaki S.,Red Cross | Inamoto Y.,Nagoya University | Sakamaki H.,Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital | Kurokawa M.,University of Tokyo | And 15 more authors.
Blood | Year: 2010

To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia (Ph- ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph- ALL patients using the registry data, particularly the details of 641 patients transplanted in CR1. Overall survival was significantly superior among patients transplanted in CR1, but no significant difference was observed between related and unrelated allo-SCTs (related vs unrelated: 65% vs 62% at 4 years, respectively; P = .19). Among patients transplanted in CR1, relapse rates were significantly higher in related allo-SCT compared with unrelated allo-SCT, and multivariate analysis demonstrated that less than 6 months from diagnosis to allo-SCT alone was associated with relapse. On the other hand, nonrelapse mortality (NRM) was significantly higher in unrelated allo-SCT compared with related allo-SCT, and multivariate analysis demonstrated that 10 months or longer from diagnosis to allo-SCT, human leukocyte antigen mismatch, and abnormal karyotype were associated with NRM. In conclusion, our study showed comparable survival rates but different relapse rates, NRM rates, and risk factors between related and unrelated allo-SCTs. After a close consideration of these factors, the outcome of allo-SCT for adult Ph- ALL in CR1 could be improved. © 2010 by The American Society of Hematology. Source


Kanda Y.,Jichi Medical University | Kanda J.,Jichi Medical University | Atsuta Y.,Nagoya University | Maeda Y.,Okayama University of Science | And 11 more authors.
British Journal of Haematology | Year: 2013

A previous Japanese study revealed that a human leucocyte antigen (HLA)-A or -B allele mismatch was associated with higher overall mortality, whereas an HLA-C or -DRB1 allele mismatch did not affect mortality after serologically matched unrelated bone marrow transplantation (BMT). This study reanalysed 3003 adult patients who underwent unrelated BMT from a serologically HLA-A, -B, or -DR matched unrelated donor between 1993 and 2009 using the latest database, that included 1966 HLA-matched unrelated BMT and 187, 31, 524, and 295 unrelated BMT with a single HLA-A, -B, -C, or -DRB1 allele mismatch, respectively. As opposed to our previous findings, HLA-C and -DRB1 mismatches had a significant negative impact [hazard ratio (HR) 1·35, P<0·001, and HR 1·45, P<0·001] on survival in the period 2000-2009. The negative impact of each single HLA allele mismatch was not significantly different among the HLA-A, -B, -C, and -DRB1 mismatches (P=0·79). An interaction test revealed that the effects of single HLA-C and -DRB1 allele mismatches significantly differed over the two time periods (P=0·032 and P=0·0072, respectively). In conclusion, the impact of a single HLA allele mismatch changed over time. In the recent cohort, the negative impact of HLA-DRB1 and -C mismatches became apparent. © 2013 John Wiley & Sons Ltd. Source


Morishima Y.,Aichi Cancer Center Research Institute | Kashiwase K.,Red Cross | Matsuo K.,Kyushu University | Azuma F.,Red Cross | And 16 more authors.
Blood | Year: 2015

We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLADQB1 double (DRB1-DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1-DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1-DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection. © 2015 by The American Society of Hematology. Source


Espinoza J.L.,Kanazawa University | Takami A.,Kanazawa University | Onizuka M.,Tokai University | Kawase T.,Aichi Cancer Center Hospital | And 10 more authors.
Bone Marrow Transplantation | Year: 2011

IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P=.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI, 0.75-45.72; P=.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P=.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD. © 2011 Macmillan Publishers Limited All rights reserved. Source

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