| 1. |
Hirabayashi S, Kosugi S, Isobe Y, Nashimoto A, Oda I, Hayashi K, Miyashiro I, Tsujitani S, Kodera Y, Seto Y, Furukawa H, Ono H, Tanabe S, Akazawa K, Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer., Annals of oncology : official journal of the European Society for Medical Oncology, 10.1093/annonc/mdu125, 25, 6, 1179-84, 2014.06, BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P |
| 2. |
Takiuchi Y, Kobayashi M, Tada K, Iwai F, Sakurada M, Hirabayashi S, Nagata K, Shirakawa K, Shindo K, Yasunaga JI, Murakawa Y, Rajapakse V, Pommier Y, Takaori-Kondo A, HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia., Scientific reports, 10.1038/s41598-017-12924-0, 7, 1, 12849-12849, 2017.10, Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). We recently reported that abacavir, an anti-HIV-1 drug, potently and selectively kills ATL cells. This effect was attributed to the reduced expression of tyrosyl-DNA-phosphodiesterase 1 (TDP1), a DNA repair enzyme, in ATL cells. However, the molecular mechanism underlying the downregulation of TDP1 in ATL cells remains elusive. Here we identified the core promoter of the TDP1 gene, which contains a conserved nuclear respiratory factor 1 (NRF-1) binding site. Overexpression of NRF-1 increased TDP1-promoter activity, whereas the introduction of dominant-negative NRF-1 repressed such activity. Overexpression of NRF-1 also upregulated endogenous TDP-1 expression, while introduction of shNRF-1 suppressed TDP1 in Jurkat T cells, making them susceptible to abacavir. These results indicate that NRF-1 is a positive transcriptional regulator of TDP1-gene expression. Importantly, we revealed that HTLV-1 bZIP factor (HBZ) protein which is expressed in all ATL cases physically interacts with NRF-1 and inhibits the DNA-binding ability of NRF-1. Taken together, HBZ suppresses TDP1 expression by inhibiting NRF-1 function in ATL cells. The HBZ/NRF-1/TDP1 axis provides new therapeutic targets against ATL and might explain genomic instability leading to the pathogenesis of ATL.. |
| 3. |
Tanabe S, Hirabayashi S, Oda I, Ono H, Nashimoto A, Isobe Y, Miyashiro I, Tsujitani S, Seto Y, Fukagawa T, Nunobe S, Furukawa H, Kodera Y, Kaminishi M, Katai H, Gastric cancer treated by endoscopic submucosal dissection or endoscopic mucosal resection in Japan from 2004 through 2006: JGCA nationwide registry conducted in 2013., Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 10.1007/s10120-017-0699-4, 20, 5, 834-842, 2017.09, BACKGROUND: The Japanese Gastric Cancer Association (JGCA) initiated a new nationwide gastric cancer registry in 2008 and reported the treatment outcomes of patients with primary gastric cancer who underwent surgical therapy in 2001 and 2003. However, the outcomes of endoscopic therapy have not been reported yet. METHODS: The JGCA conducted a retrospective nationwide registry in 2013 to investigate the short-term and long-term outcomes of endoscopic mucosal resection or endoscopic submucosal dissection in patients with gastric cancer treated from January 2004 through December 2006. This registry used a computerized database with terminology in accordance with the JGCA classification (13th and 14th editions) and the Japanese Gastric Cancer Treatment Guidelines from 2010. RESULTS: Accurate data on 12,647 patients were collected from 126 participating hospitals and analyzed. The treatment procedure was endoscopic submucosal dissection in 81% of the patients and endoscopic mucosal resection in 19%. En bloc and R0 resections were achieved in 89% and 79% of the patients respectively. The total proportion of patients who underwent curative resection was 69.2%; 43.8% of patients underwent curative resection for absolute indication lesions, and 25.4% underwent curative resection for expanded indication lesions. Emergency surgery was performed to treat bleeding or perforation in very few patients (0.3% and 0.4% respectively). The 5-year follow-up rate after endoscopic resection was 70%. The 5-year overall survival rate was 91.6% in patients with absolute indications and 90.3% in patients with expanded indications after curative resection and 86.5% in patients who underwent noncurative resection. The 5-year disease-specific survival rates were 99.9%, 99.7%, and 98.7% in patients with absolute indications who underwent curative resection, patients with expanded indications who underwent curative resection, and patients who underwent noncurative resection respectively. CONCLUSION: Endoscopic resection of gastric cancer resulted in favorable short-term and long-term outcomes nationwide in Japan. Further efforts to increase the follow-up rate are needed.. |
| 4. |
Shigeki Hirabayashi, Shruti Bhagat, Yu Matsuki, Yujiro Takegami, Takuya Uehata, Ai Kanemaru, Masayoshi Itoh, Kotaro Shirakawa, Akifumi Takaori-Kondo, Osamu Takeuchi, Piero Carninci, Shintaro Katayama, Yoshihide Hayashizaki, Juha Kere, Hideya Kawaji, Yasuhiro Murakawa, NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements, Nature Genetics, 10.1038/s41588-019-0485-9, 51, 9, 1369-1379, 2019.09, Promoters and enhancers are key cis-regulatory elements, but how they operate to generate cell type-specific transcriptomes is not fully understood. We developed a simple and robust method, native elongating transcript-cap analysis of gene expression (NET-CAGE), to sensitively detect 5' ends of nascent RNAs in diverse cells and tissues, including unstable transcripts such as enhancer-derived RNAs. We studied RNA synthesis and degradation at the transcription start site level, characterizing the impact of differential promoter usage on transcript stability. We quantified transcription from cis-regulatory elements without the influence of RNA turnover, and show that enhancer-promoter pairs are generally activated simultaneously on stimulation. By integrating NET-CAGE data with chromatin interaction maps, we show that cis-regulatory elements are topologically connected according to their cell type specificity. We identified new enhancers with high sensitivity, and delineated primary locations of transcription within super-enhancers. Our NET-CAGE dataset derived from human and mouse cells expands the FANTOM5 atlas of transcribed enhancers, with broad applicability to biomedical research.. |
| 5. |
Hiroyuki Yamazaki, Kotaro Shirakawa, Tadahiko Matsumoto, Shigeki Hirabayashi, Yasuhiro Murakawa, Masayuki Kobayashi, Anamaria Daniela Sarca, Yasuhiro Kazuma, Hiroyuki Matsui, Wataru Maruyama, Hirofumi Fukuda, Ryutaro Shirakawa, Keisuke Shindo, Masaki Ri, Shinsuke Iida, Akifumi Takaori-Kondo, Endogenous APOBEC3B Overexpression Constitutively Generates DNA Substitutions and Deletions in Myeloma Cells, Scientific Reports, 10.1038/s41598-019-43575-y, 9, 1, 7122-7122, 2019.05, Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) DNA cytosine deaminases have emerged as potential genomic mutators in various cancers. Multiple myeloma accumulates APOBEC signature mutations as it progresses; however, the mechanisms underlying APOBEC signature acquisition and its consequences remain elusive. In this study, we examined the significance and clinical impact of APOBEC3B (A3B) activity in multiple myeloma. Among APOBECs, only highly expressed A3B was associated with poor prognosis in myeloma patients, independent of other known poor prognostic factors. Quantitative PCR revealed that CD138-positive primary myeloma cells and myeloma cell lines exhibited remarkably high A3B expression levels. Interestingly, lentiviral A3B knockdown prevented the generation of deletion and loss-of-function mutations in exogenous DNA, whereas in control cells, these mutations accumulated with time. A3B knockdown also decreased the basal levels of γ-H2AX foci, suggesting that A3B promotes constitutive DNA double-strand breaks in myeloma cells. Importantly, among control shRNA-transduced cells, we observed the generation of clones that harboured diverse mutations in exogenous genes and several endogenous genes frequently mutated in myeloma, including TP53. Taken together, the results suggest that A3B constitutively mutates the tumour genome beyond the protection of the DNA repair system, which may lead to clonal evolution and genomic instability in myeloma.. |
| 6. |
Tachibana T, Najima Y, Akahoshi Y, Hirabayashi S, Harada K, Doki N, Uchida N, Fukuda T, Sawa M, Ogata M, Takada S, Tanaka M, Matsuhashi Y, Tanaka J, dummy-AUTHOR_name, Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation, The impacts of BCR-ABL1 mutations in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent allogeneic hematopoietic cell transplantation., Annals of hematology, 10.1007/s00277-020-04212-1, 99, 10, 2393-2404, 2020.08, The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCR-ABL1 mutations prior to the first allogeneic hematopoietic cell transplantation (HCT). The cohort included 289 patients with a median of 48 years of age (range: 16-70). Point mutations were detected in 110 patients. Of these, 90 (82%) harbored T315I mutations, while 20 had other mutations. With a median follow-up period of 29 months (range: 1-125), outcomes after 2 years were worse with mutations than without (overall survival [OS]: 34% vs 68%, p |
| 7. |
Yanada M, Konuma T, Yamasaki S, Mizuno S, Hirabayashi S, Nishiwaki S, Uchida N, Doki N, Tanaka M, Ozawa Y, Sawa M, Eto T, Kawakita T, Ota S, Yano S, The differential effect of disease status at allogeneic hematopoietic cell transplantation on outcomes in acute myeloid and lymphoblastic leukemia., Annals of hematology, 10.1007/s00277-021-04661-2, 100, 12, 3017-3027, 2021.09, This study aimed to compare the effect of disease status at the time of allogeneic hematopoietic cell transplantation (HCT) on post-transplant outcomes between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Japanese nationwide registry data for 6901 patients with AML and 2469 patients with ALL were analyzed. In this study, 2850 (41%), 937 (14%), 62 (1%), and 3052 (44%) AML patients and 1751 (71%), 265 (11%), 23 (1%), and 430 (17%) ALL patients underwent transplantation in first complete remission (CR1), second CR (CR2), third or subsequent CR (CR3 +), and non-CR, respectively. The probabilities of overall survival at 5 years for patients transplanted in CR1, CR2, CR3 + , and non-CR were 58%, 61%, 41%, and 26% for AML patients and 67%, 45%, 20%, and 21% for ALL patients, respectively. Multivariate analyses revealed that the risks of relapse and overall mortality were similar for AML patients transplanted in CR1 and CR2 (P = 0.672 and P = 0.703), whereas they were higher for ALL patients transplanted in CR2 than for those transplanted in CR1 (P |
| 8. |
Momoko Nakamura, Yasuyuki Arai, Shigeki Hirabayashi, Tadakazu Kondo, Noriko Doki, Naoyuki Uchida, Takahiro Fukuda, Yukiyasu Ozawa, Masatsugu Tanaka, Masashi Sawa, Yuta Katayama, Yoshinobu K, a, Souichi Shiratori, Hirohisa Nakamae, Satoshi Yoshioka, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta, Shinichi Kako, Residual disease is a strong prognostic marker in patients with acute lymphoblastic leukaemia with chemotherapy‐refractory or relapsed disease prior to allogeneic stem cell transplantation, British Journal of Haematology, 10.1111/bjh.17646, 194, 2, 403-413, 2021.06, Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is one of the curative treatment options for acute lymphoblastic leukaemia (ALL). However, the outcomes in patients transplanted without complete remission (non-CR) have not yet been fully reported, and detailed analyses are required to identify subgroups in which optimal prognosis is expected and to optimize pre-transplant therapeutic strategies. Hence, we performed a multicentred retrospective cohort study including a total of 663 adult ALL patients transplanted at non-CR status; the median bone marrow (BM) blast counts at HSCT was 13·2%, and 203 patients (30·6%) were treated at primary induction failure status. The overall survival (OS) was 31·1% at two years, and the multivariate analyses identified five prognostic risk factors, including older age (≥50 years), increased BM blasts (≥10%), poor performance status, high haematopoietic cell transplantation (HCT)-comorbidity index, and relapsed disease status, among which BM blast was the most significantly related. A predictive scoring system composed of these risk factors clearly stratified OS (15·6-59·5% at two years). In conclusion, this is the first large-scale study to analyze the correlation of patient characteristics with post-transplant prognosis in ALL transplanted at non-CR status. The importance of blast control before HSCT should be focused on for better patient prognosis.. |
| 9. |
Satoshi Nishiwaki, Yu Akahoshi, Shuichi Mizuta, Akihito Shinohara, Shigeki Hirabayashi, Yuma Noguchi, Takahiro Fukuda, Naoyuki Uchida, Masatsugu Tanaka, Makoto Onizuka, Yukiyasu Ozawa, Shuichi Ota, Souichi Shiratori, Yasushi Onishi, Yoshinobu Kanda, Masashi Sawa, Junji Tanaka, Yoshiko Atsuta, Shinichi Kako, Measurable residual disease affects allogeneic hematopoietic cell transplantation in Ph+ ALL during both CR1 and CR2, Blood Advances, 10.1182/bloodadvances.2020003536, 5, 2, 584-592, 2021.01, Although measurable residual disease (MRD) at the time of allogeneic hematopoietic cell transplantation (allo-HCT) has been reported to be an important prognostic factor for Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) during first complete remission (CR1), the prognostic impact of MRD is unclear during second CR (CR2). To clarify the impact of MRD for both CR1 and CR2, we analyzed data from a registry database including 1625 adult patients with Ph+ ALL who underwent first allo-HCT during either CR1 or CR2 between 2002 and 2017. Adjusted overall and leukemia-free survival rates at 4 years were 71% and 64%, respectively, for patients undergoing allo-HCT during CR1 with MRD-, 55% and 43% during CR1 with MRD+, 51% and 49% during CR2 with MRD-, and 38% and 29% during CR2 with MRD+. Although survival rates were significantly better among patients with CR1 MRD- than among patients with CR2 MRD-, no significant difference was observed in survival rate between patients with CR1 MRD+ and CR2 MRD-. Relapse rates after 4 years were 16% in patients with CR1 MRD-, 29% in CR1 MRD+, 21% in patients with CR2 MRD-, and 46% in patients with CR2 MRD+. No significant difference was identified in relapse rate between patients with CR1 MRD- and CR2 MRD-. CR2 MRD- was not a significant risk factor for relapse in multivariate analysis (hazard ratio, 1.26; 95% confidence interval, 0.69-2.29; P = .45 vs CR1 MRD-). MRD at time of allo-HCT was an important risk factor in patients with Ph+ ALL during both CR1 and CR2.. |
| 10. |
Takaaki Konuma, Junya Kanda, Yachiyo Kuwatsuka, Masamitsu Yanada, Tadakazu Kondo, Shigeki Hirabayashi, Shinichi Kako, Yu Akahoshi, Naoyuki Uchida, Noriko Doki, Yukiyasu Ozawa, Masatsugu Tanaka, Tetsuya Eto, Masashi Sawa, Satoshi Yoshioka, Takafumi Kimura, Yoshinobu Kanda, Takahiro Fukuda, Yoshiko Atsuta, Fumihiko Kimura, Differential effect of graft-versus-host disease on survival in acute leukemia according to donor type, Clinical Cancer Research, 10.1158/1078-0432.CCR-20-4856, 27, 17, 4825-4835, 2021.06, PURPOSE: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source. EXPERIMENTAL DESIGN: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia (n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)]. RESULTS: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I-II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P |
| 11. |
Shimomura Y, Hara M, Hirabayashi S, Kondo T, Mizuno S, Uchida N, Mukae J, Kawakita T, Fukuda T, Kanda Y, Ota S, Ozawa Y, Eto T, Maruyama Y, Tanaka M, Yanada M, Comparison of fludarabine, a myeloablative dose of busulfan, and melphalan vs conventional myeloablative conditioning regimen in patients with relapse and refractory acute myeloid leukemia in non-remission status., Bone marrow transplantation, 10.1038/s41409-021-01380-0, 2021.06. |
| 12. |
Kanda J, Hirabayashi S, Yokoyama H, Kawase T, Tanaka H, Uchida N, Taniguchi S, Takahashi S, Onizuka M, Tanaka M, Sugio Y, Eto T, Kanda Y, Kimura T, Japanese Society for Transplantation and Cellular Therapy's HLA Working Group, Effect of Multiple HLA Locus Mismatches on Outcomes after Single Cord Blood Transplantation., Transplantation and cellular therapy, 10.1016/j.jtct.2022.05.005, 28, 7, 398.e1-398.e9, 2022.05, The effect of single or multiple mismatches at each HLA locus on outcomes after cord blood transplantation (CBT) is controversial. We analyzed the effects of single or multiple HLA locus mismatches on the outcomes after single CBT using Japanese registry data from the Japan Society for Hematopoietic Cell Transplantation. Patients age ≥16 years with acute leukemia and myelodysplastic syndromes who underwent their first CBT between 2003 and 2017 (n = 4074) were included. The effect of the number of HLA locus mismatches (0, 1, or 2 for the HLA-A, -B, -C, and -DRB1 loci) on outcomes was analyzed after adjusting for other significant variables. The patient cohort had a median age of 54 years. The median total nucleated and CD34 cell doses were 2.6 × 107/kg and .8 × 105/kg, respectively. The number of CBTs with single or double mismatches were 2099 and 292, respectively, for the HLA-A locus, 2699 and 341 for the HLA-B locus, 2555 and 609 for the HLA-C locus, and 2593 and 571 for the HLA-DRB1 locus. Single and double HLA-DRB1 mismatches were associated with a higher risk of grade II-IV acute graft-versus-host disease (GVHD; single: hazard ratio [HR], 1.29, P |
| 13. |
Fumihiko Nakao, Kiyoko Setoguchi, Yuichiro Semba, Takuji Yamauchi, Jumpei Nogami, Kensuke Sasaki, Hiroshi Imanaga, Tatsuya Terasaki, Manaka Miyazaki, Shigeki Hirabayashi, Kohta Miyawaki, Yoshikane Kikushige, Takeshi Masuda, Koichi Akashi, Takahiro Maeda, Targeting a mitochondrial E3 ubiquitin ligase complex to overcome AML cell-intrinsic Venetoclax resistance., Leukemia, 10.1038/s41375-023-01879-z, 2023.03, To identify molecules/pathways governing Venetoclax (VEN) sensitivity, we performed genome-wide CRISPR/Cas9 screens using a mouse AML line insensitive to VEN-induced mitochondrial apoptosis. Levels of sgRNAs targeting March5, Ube2j2 or Ube2k significantly decreased upon VEN treatment, suggesting synthetic lethal interaction. Depletion of either Ube2j2 or Ube2k sensitized AML cells to VEN only in the presence of March5, suggesting coordinate function of the E2s Ube2j2 and Ube2k with the E3 ligase March5. We next performed CRISPR screens using March5 knockout cells and identified Noxa as a key March5 substrate. Mechanistically, Bax released from Bcl2 upon VEN treatment was entrapped by Mcl1 and Bcl-XL and failed to induce apoptosis in March5 intact AML cells. By contrast, in March5 knockout cells, liberated Bax did not bind to Mcl1, as Noxa likely occupied Mcl1 BH3-binding grooves and efficiently induced mitochondrial apoptosis. We reveal molecular mechanisms underlying AML cell-intrinsic VEN resistance and suggest a novel means to sensitize AML cells to VEN.. |
| 14. |
Maki Sakurada-Aono, Takashi Sakamoto, Masayuki Kobayashi, Yoko Takiuchi, Fumie Iwai, Kohei Tada, Hiroyuki Sasanuma, Shigeki Hirabayashi, Yasuhiro Murakawa, Kotaro Shirakawa, Chihiro Sakamoto, Keisuke Shindo, Jun-Ichirou Yasunaga, Masao Matsuoka, Yves Pommier, Shunichi Takeda, Akifumi Takaori-Kondo, HTLV-1 bZIP factor impairs DNA mismatch repair system., Biochemical and biophysical research communications, 10.1016/j.bbrc.2023.03.049, 657, 43-49, 2023.03, Adult T-cell leukemia (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). Microsatellite instability (MSI) has been observed in ATL cells. Although MSI results from impaired mismatch repair (MMR) pathway, no null mutations in the genes encoding MMR factors are detectable in ATL cells. Thus, it is unclear whether or not impairment of MMR causes the MSI in ATL cells. HTLV-1 bZIP factor (HBZ) protein interacts with numerous host transcription factors and significantly contributes to disease pathogenesis and progression. Here we investigated the effect of HBZ on MMR in normal cells. The ectopic expression of HBZ in MMR-proficient cells induced MSI, and also suppressed the expression of several MMR factors. We then hypothesized that the HBZ compromises MMR by interfering with a transcription factor, nuclear respiratory factor 1 (NRF-1), and identified the consensus NRF-1 binding site at the promoter of the gene encoding MutS homologue 2 (MSH2), an essential MMR factor. The luciferase reporter assay revealed that NRF-1 overexpression enhanced MSH2 promoter activity, while co-expression of HBZ reversed this enhancement. These results supported the idea that HBZ suppresses the transcription of MSH2 by inhibiting NRF-1. Our data demonstrate that HBZ causes impaired MMR, and may imply a novel oncogenesis driven by HTLV-1.. |
| 15. |
Nakao F, Setoguchi K, Semba Y, Yamauchi T, Nogami J, Sasaki K, Imanaga H, Terasaki T, Miyazaki M, Hirabayashi S, Miyawaki K, Kikushige Y, Masuda T, Akashi K, Maeda T., Targeting a mitochondrial E3 ubiquitin ligase complex to overcome AML cell-intrinsic Venetoclax resistance., Leukemia, 10.1038/s41375-023-01879-z, 2023.05. |
| 16. |
Shimomura, Yoshimitsu; Sobue, Tomotaka; Hirabayashi, Shigeki; Kondo, Tadakazu; Mizuno, Shohei; Kanda, Junya; Fujino, Takahiro; Kataoka, Keisuke; Uchida, Naoyuki; Eto, Tetsuya; Miyakoshi, Shigesaburo; Tanaka, Masatsugu; Kawakita, Toshiro; Yokoyama, Hisayuki; Doki, Noriko; Harada, Kaito; Wake, Atsushi; Ota, Shuichi; Takada, Satoru; Takahashi, Satoshi; Kimura, Takafumi; Onizuka, Makoto; Fukuda, Takahiro; Atsuta, Yoshiko; Yanada, Masamitsu, Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia, LEUKEMIA, 10.1038/s41375-021-01474-0, 36, 4, 1132-1138, 2021.11, Cord blood transplantation (CBT) is an alternative donor transplantation method and has the advantages of rapid availability and the possibility of inducing a more potent graft-versus-leukemia effect, leading to a lower relapse rate for patients with non-remission relapse and refractory acute myeloid leukemia (R/R AML). This study aimed to investigate the impact of CBT, compared to human leukocyte antigen-matched related donor transplantation (MRDT). This study included 2451 adult patients with non-remission R/R AML who received CBT (1738 patients) or MRDT (713 patients) between January 2009 and December 2018. Five-year progression-free survival (PFS) and the prognostic impact of CBT were evaluated using a propensity score (PS) matching analysis. After PS matching, the patient characteristics were well balanced between the groups. The five-year PFS was 25.2% (95% confidence interval [CI]: 21.2–29.5%) in the CBT group and 18.1% (95% CI: 14.5–22.0%) in the MRDT group (P = 0.009). The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.69–1.00, P = 0.045); this was due to a more pronounced decrease in the relapse rate (HR: 0.78, 95% CI: 0.69–0.89, P |
| 17. |
Konuma, Takaaki; Kanda, Junya; Kuwatsuka, Yachiyo; Yanada, Masamitsu; Kondo, Tadakazu; Hirabayashi, Shigeki; Kako, Shinichi; Akahoshi, Yu; Uchida, Naoyuki; Doki, Noriko; Ozawa, Yukiyasu; Tanaka, Masatsugu; Eto, Tetsuya; Sawa, Masashi; Yoshioka, Satoshi; Kimura, Takafumi; Kanda, Yoshinobu; Fukuda, Takahiro; Atsuta, Yoshiko; Kimura, Fumihiko, Differential Effect of Graft-versus-Host Disease on Survival in Acute Leukemia according to Donor Type, CLINICAL CANCER RESEARCH, 10.1158/1078-0432.CCR-20-4856, 27, 17, 4825-4835, 2021.09, Purpose: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source.
Experimental design: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia (n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)].
Results: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I-II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P
Conclusions: These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia.. |
| 18. |
Hirabayashi, Shigeki; Kondo, Tadakazu; Oka, Tomomi; Akamatsu, Yuri; Hishizawa, Masakatsu; Shibata, Toshiya; Kitano, Toshiyuki; Takaori-Kondo, Akifumi, Successful treatment of severe acute gastrointestinal graft-versus-host disease complicated by cytomegalovirus gastroenteritis with intra-arterial steroid infusion, ANNALS OF HEMATOLOGY, 10.1007/s00277-016-2686-y, 95, 8, 1373-1375, 2016.08. |
| 19. |
Hirabayashi, Shigeki; Uozumi, Ryuji; Kondo, Tadakazu; Arai, Yasuyuki; Kawata, Takahito; Uchida, Naoyuki; Marumo, Atsushi; Ikegame, Kazuhiro; Fukuda, Takahiro; Eto, Tetsuya; Tanaka, Masatsugu; Wake, Atsushi; Kanda, Junya; Kimura, Takafumi; Tabuchi, Ken; Ichinohe, Tatsuo; Atsuta, Yoshiko; Yanada, Masamitsu; Yano, Shingo, Personalized prediction of overall survival in patients with AML in non-complete remission undergoing allo-HCT, CANCER MEDICINE, 10.1002/cam4.3920, 10, 13, 4250-4268, 2021.07. |
| 20. |
Hirabayashi S, Shirakawa K, Horisawa Y, Matsumoto T, Matsui H, Yamazaki H, Sarca AD, Kazuma Y, Nomura R, Konishi Y, Takeuchi S, Stanford E, Kawaji H, Murakawa Y, Takaori-Kondo A, APOBEC3B is preferentially expressed at the G2/M phase of cell cycle, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2021.02.008, 546, 178-184, 2021.03. |
| 21. |
Hirabayashi S, Bhagat S, Matsuki Y, Takegami Y, Takuya U, Kanemaru A, Itoh M, Shirakawa K, Takaori-Kondo A, Takeuchi O, Carninci P, Katayama S, Hayashizaki Y, Kere J, Kawaji H, Murakawa Y., NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements, NATURE GENETICS, 10.1038/s41588-019-0485-9, 51, 9, 1369-+, 2019.09. |
| 22. |
Hirabayashi S, Kosugi S, Isobe Y, Nashimoto A, Oda I, Hayashi K, Miyashiro I, Tsujitani S, Kodera Y, Seto Y, Furukawa H, Ono H, Tanabe S, Kaminishi M, Nunobe S, Fukagawa T, Matsuo R, Nagai T, Katai H, Wakai T, Akazawa K., Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer, ANNALS OF ONCOLOGY, 10.1093/annonc/mdu125, 25, 6, 1179-1184, 2014.06. |
