Publications by authors named "Shuichi Ota"

109 Publications

Mixed Chimerism and Secondary Graft Failure in Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia.

Biol Blood Marrow Transplant 2020 03 13;26(3):445-450. Epub 2019 Oct 13.

Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Mixed chimerism (MC) and/or secondary graft failure (SGF) with recipient- or donor-type chimerism is a major obstacle in allogeneic transplantation for aplastic anemia (AA). From a registry database in Japan, patients with AA age >15 years who underwent a first allogeneic bone marrow or peripheral blood stem cell transplantation between 2000 and 2014 and achieved engraftment were included in this study. MC that did not require either granulocyte-colony stimulating factor (G-CSF) or transfusion support (group 1), MC (not SGF) that required G-CSF and/or transfusion support (group 2), SGF with MC or complete recipient-type chimerism (group 3), and SGF with complete donor-type chimerism (group 4) developed in 26, 16, 19, and 17 patients, respectively. The overall median duration of follow-up for survivors was 1727 days. The overall survival (OS) was 90.4% at 1 year and 83.5% at 5 years in patients without MC or SGF (n = 340), which was not different from the OS in groups 1 and 2. However, inferior OS was observed in group 3 (1 year, 52.1%; 5 years, 52.1%) and group 4 (1 year, 82.4%; 5 years, 56.3%). In multivariate analyses, the use of fludarabine (Flu) and the absence of irradiation in conditioning were associated with the development of SGF with MC or complete recipient-type chimerism, and the use of Flu in conditioning was associated with SGF with complete donor-type chimerism. In conclusion, the use of Flu may affect the occurrence of SGF with both recipient-type and donor-type chimerism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2019.10.004DOI Listing
March 2020

Time-Varying Effects of Graft Type on Outcomes for Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2020 02 9;26(2):307-315. Epub 2019 Oct 9.

Department of Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan.

This study aimed to investigate time-varying effects of graft type on outcomes for patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant. For this purpose we analyzed 3952 patients, 720 of whom underwent matched related bone marrow transplantation (BMT), 1004 matched related peripheral blood stem cell transplantation (PBSCT), 856 matched unrelated BMT, and 1372 umbilical cord blood transplantation (UCBT) during complete remission. The 4-year relapse-free survival (RFS) rates were 59.1%, 52.8%, 59.5%, and 50.6%, respectively. Compared with related BMT, related PBSCT, unrelated BMT, and UCBT were associated with higher risk of nonrelapse mortality and unrelated BMT and UCBT with lower risk of relapse. As a result, both RFS and overall survival were comparable between related BMT and unrelated BMT but were worse for related PBSCT and UCBT than for related BMT. Adverse impact of UCBT was observed only during the early phase of transplant, whereas that of related PBSCT continued even after 2 years post-transplant. Our findings raise concerns about the increased risk of late nonrelapse mortality with the use of PBSC grafts and suggest that related BMT is preferable to related PBSCT; matched unrelated BMT is the next choice in the absence of a matched related donor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2019.09.036DOI Listing
February 2020

Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome.

Biol Blood Marrow Transplant 2020 01 20;26(1):139-144. Epub 2019 Sep 20.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P < .001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2019.09.021DOI Listing
January 2020

[Locally Advanced Sigmoid Colon Cancer in an Elderly Patient Treated with Curative Resection after Successful Panitumumab Treatment].

Gan To Kagaku Ryoho 2019 Aug;46(8):1311-1313

Dept. of Surgery, Uji Takeda Hospital.

An 84-year-old woman had locally advanced sigmoid colon cancer that was unresectable because of deep invasion in the left pelvic wall. Transverse double-barrel colostomy was performed owing to stenosis in the sigmoid colon. The patient's performance status score was 2, and it was difficult to administer cytotoxic chemotherapy. Single-agent panitumumab chemotherapy was initiated. In addition, although S-1 was administered for 4 days in the fourth cycle, it was discontinued owing to drug intolerance. Panitumumab was administered seven times. The tumor size markedly reduced, and sigmoid colectomy was performed. Thus, single-agent panitumumab chemotherapy is a possible treatment option for advanced colorectal cancer in elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2019

Clinical efficacy and safety of first-line nilotinib therapy and evaluation of the clinical utility of the FRET-based drug sensitivity test.

Int J Hematol 2019 Oct 25;110(4):482-489. Epub 2019 Jun 25.

Department of Hematology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Nilotinib is widely used for primary treatment of patients with chronic myelogenous leukemia (CML). We previously reported that use of an FRET-based drug sensitivity test at diagnosis efficiently predicts the response to treatment with imatinib or dasatinib. Here, we conducted a phase-II study to evaluate the efficacy and safety of nilotinib treatment and identify useful biomarkers, including results of the FRET-based drug sensitivity test, for predicting treatment response. Data from 42 patients were used in the analysis. Major molecular response (MMR), MR4, and MR4.5 rates at 12 months were 64.3, 42.9, and 28.6%, respectively. Grade 3/4 non-hematologic adverse events occurred in 11 patients (26.2%). The dose intensity of nilotinib (> 76.44%) and halving time (HT, < 13.312 days) were identified as significant factors for MMR at 12 months. However, when we focused on patients whose dose intensity of nilotinib was > 76.44%, the FRET-based drug sensitivity test became a predictive factor of MR4 achievement at 12 months. Our study reconfirmed the efficacy and safety of nilotinib treatment in CML patients. Moreover, our results suggest that the FRET-based drug sensitivity test is an independent predictor for achievement of MR4 in patients treated with a sufficient dose intensity of nilotinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-019-02696-wDOI Listing
October 2019

BM is preferred over PBSCs in transplantation from an HLA-matched related female donor to a male recipient.

Blood Adv 2019 06;3(11):1750-1760

Department of Hematology, Oita University Hospital, Oita, Japan.

The use of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells (PBSCs) and sex-mismatched hematopoietic cell transplantation (HCT), especially with female donors and male recipients (FtoM), is known to be associated with an increased risk of chronic graft-versus-host disease (GVHD) compared with transplantation with bone marrow (BM). This raises the question of whether the use of PBSCs in FtoM HCT might affect allogeneic responses, resulting in fatal complications. Using a Japanese transplantation registry database, we analyzed 1132 patients (FtoM, n = 315; MtoF, n = 260; sex-matched, n = 557) with standard-risk diseases who underwent HCT with an HLA-matched related donor without in vivo T-cell depletion between 2013 and 2016. The impact of PBSC vs BM on transplantation outcomes was separately assessed in FtoM, MtoF, and sex-matched HCT. Overall survival (OS) and nonrelapse mortality (NRM) at 2 years post-HCT were significantly worse in patients with PBSCs vs those with BM in FtoM HCT (2-year OS, 76% vs 62%; = .0084; 2-year NRM, 10% vs 21%; = .0078); no differences were observed for MtoF or sex-matched HCT. Multivariate analyses confirmed the adverse impact of PBSCs in FtoM HCT (hazard ratio [HR] for OS, 1.91; = .025; HR for NRM, 3.70; = .0065). In FtoM HCT, patients with PBSCs frequently experienced fatal GVHD and organ failure. In conclusion, the use of PBSCs in FtoM HCT was associated with an increased risk of NRM in the early phase, resulting in inferior survival. This suggests that, when we use female-related donors for male patients in HCT, BM may result in better outcomes than PBSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2019000077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560341PMC
June 2019

Phase I/II Pilot Study of Wilms' Tumor 1 Peptide-Pulsed Dendritic Cell Vaccination Combined With Conventional Chemotherapy in Patients With Head and Neck Cancer.

Ther Apher Dial 2019 Jun 6;23(3):279-288. Epub 2019 Jun 6.

Department of Internal Medicine, Sapporo Hokuyu Hospital, Sapporo, Japan.

The prognosis of metastatic or relapsed head and neck squamous cell carcinoma (HNSCC) remains poor despite the introduction of immune checkpoint blockade agents. We aimed to investigate the safety and the feasibility of a vaccination with Wilms' tumor 1 peptide-loaded dendritic cells (DCs) and OK-432 adjuvant combined with conventional chemotherapy. Eleven eligible patients with metastatic or relapsed HNSCC were enrolled. No severe adverse events related to a vaccination were observed. Five patients had durable stable disease and six other patients had disease progression after DC vaccination. Median progression-free survival and overall survival was 6.4 months and 12.1 months, respectively. DC vaccination augmented Wilms' tumor 1-specific immunity which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a conventional chemotherapy is safe and feasible for patients in advanced stage of HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-9987.12831DOI Listing
June 2019

ABO blood type incompatibility lost the unfavorable impact on outcome in unrelated bone marrow transplantation.

Bone Marrow Transplant 2019 10 13;54(10):1676-1685. Epub 2019 Mar 13.

Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

The effects of ABO incompatibility on hematopoietic stem cell transplantation remain controversial. Large cohorts are required to obtain findings that allow for definite conclusions. We previously demonstrated poor overall survival and increased treatment-related mortality (TRM) in ABO-incompatible unrelated bone marrow transplantation (UR-BMT) performed during the period from 1993 to 2005. To improve our understanding of ABO-incompatible transplantation, we reanalyzed the effects of ABO mismatch in a UR-BMT cohort in Japan after 2000. Multivariate analyses for the 2000-2006 cohort showed that major ABO mismatch was associated with poor overall survival (HR, 1.211; 95% CI, 1.062 to 1.381; p = 0.004) and increased TRM (HR, 1.357; 95% CI, 1.146 to 1.608; p < 0.001). In the 2007-2015 cohort, major incompatibility had no effect on overall survival (HR, 0.987, p = 0.804) or TRM (HR, 1.020, p = 0.790). Delayed engraftment of erythrocytes, platelets, and neutrophils in cases of major mismatch was common between the two cohorts. In conclusion, the adverse effect of ABO major incompatibility has become less significant over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-019-0496-2DOI Listing
October 2019

Serum level of soluble interleukin-2 receptor is positively correlated with metabolic tumor volume on F-FDG PET/CT in newly diagnosed patients with diffuse large B-cell lymphoma.

Cancer Med 2019 03 20;8(3):953-962. Epub 2019 Feb 20.

Department of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma. High total metabolic tumor volume (TMTV) calculated using F-FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of F-FDG PET/CT. In order to explore a surrogate marker for TMTV, we evaluated the correlation between the serum levels of soluble interleukin-2 receptor (sIL-2R) and TMTV in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. Serum levels of sIL-2R were significantly correlated with TMTV. ROC analysis revealed that the cutoff value of TMTV ≥150 cm or sIL-2R ≥ 1300 U/mL could predict failure to achieve EFS24 with areas under the curve (AUC) 0.706 and 0.758, respectively. Each of TMTV ≥150 cm and sIL-2R ≥1300 U/mL was significantly associated with worse 5-year overall survival and event-free survival. Importantly, each of sIL-2R <1300 U/mL or TMTV <150 cm identified patients with favorable prognosis among NCCN-IPI high-intermediate and high-risk group. Serum level of sIL-2R represents a convenient surrogate marker to estimate metabolic tumor burden measured by F-FDG PET/CT that can predict treatment outcomes of patients with DLBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.1973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434200PMC
March 2019

Clinical impact of the loss of chromosome 7q on outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem cell transplantation.

Bone Marrow Transplant 2019 09 4;54(9):1471-1481. Epub 2019 Feb 4.

Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan.

We conducted a nationwide retrospective study to evaluate the prognostic influence of +1, der(1;7)(q10;p10) [hereafter der(1;7)] and -7/del(7q) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndromes (MDS). In this database, 69 MDS patients with der(1;7), 75 with -7/del(7q), and 511 with normal karyotype (NK) underwent allo-HSCT at advanced disease status. The 3-year overall survival (OS) and cumulative incidence of relapse (CIR) were 50.4 and 19.4% for those with der(1;7), 36.2 and 38.4% for -7/del(7q), and 51.1 and 20.7% for NK, respectively. In the multivariate analysis, the presence of -7/del(7q) correlated with a significantly shorter OS (HR [95% CI], 1.38 [1.00-1.89]; P = 0.048) and higher CIR (HR, 2.11 [1.36-3.28]; P = 0.001) than those with NK. There were 23 patients with der(1;7), 29 with -7/del(7q), and 347 with NK who underwent allo-HSCT at early disease status. The 3-year OS and CIR were as follows: 47.3 and 9.5% for the der(1;7) group, 70.5 and 13.8% for -7/del(7q), and 70.9 and 5.6% for NK, respectively. No significant differences were observed in OS and CIR among three groups. The impact of the loss of chromosome 7q on OS and CIR may differ based on its type and disease status after allo-HSCT for MDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-019-0469-5DOI Listing
September 2019

Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors.

Blood Adv 2019 01;3(2):105-115

Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan.

Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors' median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; 03) with CB, whereas it improved GRFS (HR, 0.515; < .01) and decreased grades II to IV aGVHD (HR, 0.576; < .01), extensive cGVHD (HR, 0.460; = .02), and NRM (HR, 0.545; = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2018025643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341193PMC
January 2019

Effects of recombinant thrombomodulin therapy and soluble human leukocyte antigen-G levels during hematopoietic stem cell transplantation.

Transpl Immunol 2019 04 10;53:28-33. Epub 2018 Dec 10.

Kansai Medical University, Japan.

Background: Conditioning chemotherapies for hematopoietic stem cell transplantation (HSCT), especially those that include total body irradiation, can result in serious complications such as graft-versus-host disease (GVHD). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule with multiple immunoregulatory functions.

Methods: We measured interleukin (IL)-10, transforming growth factor (TGF)β, and soluble HLA-G (sHLA-G) in HSCT patients and examined the relationship between sHLA-G levels and acute GVHD (aGVHD). Additionally, we investigated the effect of recombinant soluble thrombomodulin (rTM) therapy on sHLA-G levels. Our study cohort included 135 patients who underwent allogeneic HSCT at several institutions in Japan.

Results: Serum levels of IL-10 and TGFβ exhibited no significant changes following HSCT. In contrast, levels of sHLA-G were significantly increased at days 21 and 28 post-HSCT. For patients with confirmed complications, the frequency of aGVHD was significantly lower in those with a > 2.8-fold increase in sHLA-G levels at day 28 relative to day 7 post-HSCT. sHLA-G levels in patients who received rTM therapy were significantly higher at days 21 and 28 post-HSCT compared with those in patients who did not receive rTM therapy.

Conclusion: These data suggest that HLA-G/sHLA-G participate in prevention of GVHD, and that rTM may prevent aGVHD following HSCT by promoting elevation of sHLA-G.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trim.2018.12.001DOI Listing
April 2019

HLA discrepancy between graft and host rather than that graft and first donor impact the second transplant outcome.

Haematologica 2019 05 6;104(5):1055-1061. Epub 2018 Dec 6.

Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan.

Second allogeneic hematopoietic stem cell transplantation is a curative treatment option for patients with hematologic malignancies. However, it is unclear whether HLA discrepancy between graft and first donor has an impact on the outcome of second transplantation. We retrospectively analyzed 646 patients receiving second transplantation after an initial HLA mismatched transplantation. With regard to graft--host, the one-allele mismatch (1 mismatch) group (SHR, 1.88; 95%CI: 0.79-4.45; =0.163) and more than one-allele mismatch group (≥ 2 mismatch) (SHR, 1.84; 95%CI, 0.75-4.51; =0.182) had higher risks of grade III-IV acute graft--host disease (GvHD) compared to the HLA-matched (0 mismatch) group. In contrast, no difference in risk of acute GvHD was found among the 0, 1, and ≥ 2 mismatch group with respect to graft--first donor. With regard to graft--host, the ≥ 2 mismatch group showed a significantly higher risk of treatment-related mortality (SHR, 1.90; 95%CI, 1.04-3.50; =0.038) compared to the 0 mismatch group, while the risk of relapse was slightly lower in the ≥ 2 mismatch group (SHR, 068; 95%CI, 0.44-1.06; =0.086). In contrast, with regard to graft--first donor, there were no significant differences in treatment-related mortality or relapse among the three groups. These findings suggested that HLA discrepancy between graft and host induces transplant-related immunological responses in second transplantation leading to an increase in treatment-related mortality, in contrast, the biological effects of HLA discrepancy between graft and first donor on outcome may be negligible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2018.204438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518881PMC
May 2019

Allogeneic hematopoietic stem cell transplantation for the treatment of BCR-ABL1-negative atypical chronic myeloid leukemia and chronic neutrophil leukemia: A retrospective nationwide study in Japan.

Leuk Res 2018 12 13;75:50-57. Epub 2018 Nov 13.

Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan; Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare BCR-ABL1 fusion gene-negative myeloid neoplasms with a predominance of neutrophils. Since no standard therapeutic strategy currently exists for these diseases, we retrospectively evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aCML and CNL. Data from 14 aCML and 5 CNL patients as their diagnoses were collected using a nationwide survey. Allo-HSCT was performed between 2003 and 2014. Preconditioning regimens included myeloablative (n = 15), reduced-intensity (n = 3), and non-myeloablative (n = 1) regimens. Transplanted stem cells were obtained from HLA-matched related donors (n = 5) and alternative donors (n = 14). Neutrophil engraftment was successfully achieved in 17 patients. One-year overall survival rates (OS) were 54.4% (95% confidence interval [CI], 24.8 to 76.7%) and 40.0% (95% CI, 5.2 to 75.3%) in patients with aCML and CNL, respectively. Among aCML patients, 1-year OS were 76.2% (95% CI, 33.2 to 93.5%) and 20.0% (95% CI, 0.8 to 58.2%) in patients with <5% myeloblasts (n = 9) and ≥5% myeloblasts (n = 5) in peripheral blood before allo-HSCT, respectively. These results suggest that allo-HSCT achieves long-term survival in patients with aCML and CNL. Better pre-transplant management is required to improve the outcomes of aCML patients with ≥5% blasts in peripheral blood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2018.11.003DOI Listing
December 2018

Comparison of HLA Allele Mismatch and Antigen Mismatch in Unrelated Bone Marrow Transplantation in Patients with Leukemia.

Biol Blood Marrow Transplant 2019 03 8;25(3):436-442. Epub 2018 Oct 8.

Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan. Electronic address:

We compared the effect of HLA single-antigen and single-allele mismatched unrelated bone marrow transplantation (UBMT) without in vivo/ex vivo T cell depletion. Becasue a single DRB1 mismatch is preferred among 1-allele or 1-antigen mismatched donors, we performed mismatched allele- or antigen-specific analyses with a single DRB1 mismatch as the reference. In adjusted comparison by multivariate analyses, an HLA-DRB1 single-allele mismatch resulted in a decreased risk of nonrelapse mortality (NRM; relative risk [RR], 1.33; 95% confidence interval [CI], 1.08 to 1.63, P = .006) compared with an HLA-DR single-antigen mismatch and conferred a decreased risk of NRM (RR, 1.25; 95% CI, 1.01 to 1.57; P = .025) and overall mortality (RR, 1.16; 95% CI, 1.00 to 1.37; P = .046) compared with an HLA-C single-antigen mismatch. Relative to an HLA-DRB1 single-allele mismatch, 2-mismatch transplants, including those with 1 or more antigen mismatches, resulted in a significantly increased risk of NRM (1-antigen/1-allele mismatch: RR, 1.68; 95% CI, 1.03 to 2.05; P < .001; 2-antigen mismatch: RR, 1.58; 95% CI, 1.04 to 2.02; P = .001) and overall mortality (1-antigen/1-allele mismatch: RR, 1.27; 95% CI, 1.09 to 1.47; P = .002; 2-antigen mismatch: RR, 1.27; 95% CI, 1.03 to 1.57; P = .02). NRM correlated with the combined number of mismatches and allele or antigen mismatches, with rates of 22%, 27%, 32%, 31%, and 38% at 4years for full match, single-allele mismatch, single-antigen mismatch, 2-allele mismatch, and 2 mismatches that included an antigen mismatch, respectively. Our results support the preference for an allele mismatch rather than an antigen mismatch in unrelated bone marrow donors with 1 DR mismatch or 2 mismatches for T cell-replete UBMT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2018.10.002DOI Listing
March 2019

Clinical effects of recombinant thrombomodulin and defibrotide on sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation.

Bone Marrow Transplant 2019 05 20;54(5):674-680. Epub 2018 Aug 20.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

Sinusoidal obstruction syndrome (SOS) is a lethal complication after hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is the only drug internationally recommended for SOS treatment in Western countries. Recombinant human soluble thrombomodulin (rhTM), which is promising for the treatment of patients with disseminated intravascular coagulation, is also reported to be potentially effective for SOS. To clarify the safety and efficacy of DF and rhTM, we conducted a retrospective survey of these agents in Japan. Data from 65 patients who underwent allogeneic HSCT and received DF (n  =  24) or rhTM (n  =  41) for SOS treatment were collected. The complete response rates for SOS on day 100 were 50% and 54% in the DF and rhTM groups, respectively. The 100-day overall survival rates were 50% in the DF group, and 48% in the rhTM group. Several severe hemorrhagic adverse events were observed in one patient in the DF group and five patients in the rhTM group. The main causes of death were SOS-related death, and no patient died of direct adverse events of DF or rhTM. Our results suggest that rhTM, as well as DF, can be effective as a novel treatment option for SOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-018-0304-4DOI Listing
May 2019

Patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: trends in survival during the past two decades.

Bone Marrow Transplant 2019 04 14;54(4):578-586. Epub 2018 Aug 14.

Jikei University School of Medicine, Tokyo, Japan.

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. To address this question, we conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between the 1994-2006 and 2007-2013 periods. Significant improvement in survival was observed in the later cohort compared to the earlier cohort for unrelated HCT (P = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT was solely due to diminished non-relapse mortality (P = 0.001), while incidence of relapse did not change over time (P = 0.934). The percentage of patients receiving transplants from 8/8-matched unrelated donors was significantly higher in the later cohort (P < 0.001), and their survival was significantly better than that of those undergoing mismatched unrelated HCT (P = 0.022). These findings suggest that advances in HLA-typing technology have been vital for improvement in transplantation outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-018-0301-7DOI Listing
April 2019

Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide.

Bone Marrow Transplant 2019 03 7;54(3):432-441. Epub 2018 Aug 7.

Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.

We conducted two parallel prospective, multicenter, phase II studies to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) following myeloablative conditioning (MAC, n = 50) and reduced-intensity conditioning (RIC, n = 77). Event-free survival (EFS) at 1-year as for primary endpoint was 64% and 43% in the MAC and RIC groups, respectively. Neutrophil engraftment was achieved in 98% and 94% in the MAC and RIC groups, respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 18% and 8% in the MAC group, and 14% and 5% in the RIC group, respectively. Those of all grade and moderate to severe chronic GVHD at 2-year were 36% and 20% in the MAC group, and 27% and 20% in the RIC group, respectively. Overall survival (OS), EFS, nonrelapse mortality, and relapse rate at 2-year were 68%, 54%, 10%, and 36% in the MAC group, and 44%, 35%, 20%, and 45% in the RIC group, respectively. Notably, 83% and 86% of patients who survived without relapse stopped immunosuppressant at 2-year in the MAC and RIC groups, respectively. Our results indicate that both MAC and RIC are valid options for PTCy-haploPBSCT for adults with hematological malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-018-0279-1DOI Listing
March 2019

Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia: A Hokkaido Leukemia Net Study.

Clin Lymphoma Myeloma Leuk 2018 11 17;18(11):e469-e479. Epub 2018 Jul 17.

Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan.

Background: The prognostic effect of Wilms tumor 1 (WT1) expression at the diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of the present study was to determine the correlations of WT1 expression at the diagnosis of AML with established prognostic alterations.

Patients And Methods: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, single nucleotide polymorphism (SNP) in the WT1 gene (rs16754), and Fms-like tyrosine kinase receptor-3 internal tandem duplication (FLT3-ITD) mutation were analyzed for all patients. The nucleophosmin 1 (NPM1) mutation and CCAAT/enhancer-binding protein-α (CEBPA) double mutation were analyzed for cytogenetically normal (CN)-AML. The KIT mutation was analyzed for core-binding factor AML.

Results: Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly greater than that in AML with t(8;21). In cases with CN-AML, FLT3-ITD and NPM1 mutations both correlated with greater expression of WT1, and the CEBPA double mutation was related to lower WT1 expression. The existence of both FLT3-ITD and NPM1 mutations showed synergistically greater expression of WT1 in CN-AML. SNP in the WT1 gene (rs16754) was significantly associated with lower expression of WT1. The WT1 levels were not prognostic factors in the total cohort or any cytogenetic group or stratified by SNP status.

Conclusion: Because WT1 expression has correlated with known prognostic factors, the prognostic effect of WT1 levels could be misunderstood depending on the distribution of the collaborative mutations in each cohort. We have concluded that the prognostic significance of WT1 at the diagnosis of AML is weak compared with the other established prognostic factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clml.2018.07.291DOI Listing
November 2018

Allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia with 11q23 abnormality: a retrospective study of the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT).

Ann Hematol 2018 Nov 6;97(11):2173-2183. Epub 2018 Jul 6.

Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.

An 11q23 abnormality presents in approximately 5% of adults with acute myeloid leukemia (AML) and is associated with adverse outcomes even after allogeneic hematopoietic cell transplantation (allo-HCT). To evaluate the outcomes and prognostic factors following allo-HCT for adult AML with 11q23 abnormality, we retrospectively analyzed the Japanese registration data of 322 adult AML patients with 11q23 abnormality who had received allo-HCT between 1990 and 2014. In total, the disease status at HCT was first complete remission (CR1) in 159 (49%) patients. The probability of overall survival and the cumulative incidence of relapse at 3 years were 44 and 44%, respectively. In the multivariate analysis, disease status beyond CR1 at the time of HCT was significantly associated with a higher overall mortality and relapse. The 11q23 fusion partner did not have a significant impact on survival. We also evaluated the prognostic value of minimal residual disease (MRD) status at HCT on transplant outcomes among hematological CR patients. MRD status at HCT was the significant prognostic indicator for hematological relapse and survival. These data suggested that allo-HCT offered a curative option for adult AML with 11q23 abnormality. Pretransplant MRD status was the significant prognostic indicator for relapse and survival in CR patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-018-3419-1DOI Listing
November 2018

Vaccination of Urological Cancer Patients With WT1 Peptide-Pulsed Dendritic Cells in Combination With Molecular Targeted Therapy or Conventional Chemotherapy Induces Immunological and Clinical Responses.

Ther Apher Dial 2018 Jun 30;22(3):266-277. Epub 2018 May 30.

Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.

The prognosis of metastatic or relapsed renal cell carcinoma (RCC) or bladder cancer (BC) remains poor despite the introduction of immune checkpoint blockade agents. We aimed to investigate the safety and the feasibility of a vaccination with WT1 peptide-loaded dendritic cells (DCs) and OK-432 adjuvant combined with molecular targeted therapy or conventional chemotherapy. Five eligible patients with metastatic or relapsed RCC and five eligible patients with BC were enrolled. No severe adverse events related to a vaccination were observed. Seven patients with RCC or non-muscle invasive BC had durable stable disease and three other patients had disease progression after DC vaccination. DC vaccination augmented WT1 specific immunity and the reduction of regulatory T cells which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a molecular targeted therapy or a conventional chemotherapy is safe and feasible for patients in advanced stage of RCC or BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-9987.12694DOI Listing
June 2018

Allogeneic haematopoietic cell transplantation for adult acute myeloid leukaemia in second remission: a retrospective study of the Adult Acute Myeloid Leukaemia Working Group of the Japan Society for Haematopoietic Cell Transplantation (JSHCT).

Br J Haematol 2018 07 29;182(2):245-250. Epub 2018 May 29.

Division of Clinical Oncology and Haematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.

To evaluate the outcomes and prognostic factors following allogeneic haematopoietic cell transplantation (HCT) for adult acute myeloid leukaemia (AML) in second complete remission (CR2), we retrospectively analysed the Japanese registration data of 1080 adult AML patients in CR2 who had received allogeneic HCT. The probability of overall survival and the cumulative incidence of relapse at 3 years was 66% and 19%, respectively. In multivariate analysis, older age, poor cytogenetics and shorter duration of first complete remission were significantly associated with a higher overall mortality. Our data demonstrated the significant efficacy of allogeneic HCT for adult AML in CR2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.15399DOI Listing
July 2018

Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia.

Eur J Haematol 2018 Jul 23;101(1):95-105. Epub 2018 May 23.

Department of Hematology, Hokkaido Cancer Center, Sapporo, Japan.

Objective: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome.

Methods: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014.

Results: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89.0%, respectively. Patients with comorbidities (46.4%) and aged ≥60 years (50.4%) at diagnosis had significantly inferior OS to those without comorbidities and aged <60. Patients achieved higher rates of major molecular response (MMR) at 6 and 12 months after initial treatment with dasatinib or nilotinib compared to imatinib, but final MMR rates were almost the same. Sixty-six percent of patients required treatment modifications from first-line TKI therapy; the main reasons were AEs (48.4%) and failure (18%). Grade III-IV AEs in first-line TKI therapy were significantly correlated to inferior OS/EFS compared to grade 0-II AEs.

Conclusion: Although long-term outcomes were similar in CML-CP patients treated with each TKI regardless of first-line TKI selection, severe AEs in first-line TKI therapy decreased their survival rates. Early change in TKIs is recommended, when faced with severe AEs of specific TKIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.13081DOI Listing
July 2018

Impact of HIV Infection on Transplant Outcomes after Autologous Peripheral Blood Stem Cell Transplantation: A Retrospective Study of Japanese Registry Data.

Biol Blood Marrow Transplant 2018 08 15;24(8):1596-1601. Epub 2018 Mar 15.

Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address:

Autologous stem cell transplantation (ASCT) is a treatment option for HIV-positive patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). However, the prognosis after ASCT in HIV-positive Japanese patients remains unclear. The aim of this study was to evaluate the impact of HIV infection on transplant outcomes after ASCT in Japan. Using the national database of the Japan Society for Hematopoietic Cell Transplantation, we retrospectively evaluated patients with NHL (n = 3862) and MM (n = 2670) who underwent their first ASCT between 2001 and 2014. The presence of HIV antibody was used to diagnose HIV infection. Fifty-six patients with NHL (1.4%) and 23 with MM (.8%) were positive for HIV antibody. Among patients with NHL overall survival (OS) was lower in HIV-positive patients than in HIV-negative patients (5-year OS: HIV-positive patients, 44% versus HIV-negative patients, 65%; P < .001). In a multivariate analysis HIV infection was significantly associated with an increased risk of overall mortality (hazard ratio, 2.30; P < .001). The incidence of relapse was higher in HIV-positive patients (P = .036), whereas there was a similar incidence of nonrelapse mortality (P = .879). OS in patients with MM was similar between those with/without HIV infection (5-year OS: HIV-positive patients, 61% versus HIV-negative patients, 63%; P = .988). HIV infection was associated with a higher risk of overall mortality and relapse after ASCT for NHL in a Japanese population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2018.03.009DOI Listing
August 2018

Effect of cytogenetic risk status on outcomes for patients with acute myeloid leukemia undergoing various types of allogeneic hematopoietic cell transplantation: an analysis of 7812 patients.

Leuk Lymphoma 2018 03 28;59(3):601-609. Epub 2017 Jul 28.

q Jikei University School of Medicine , Tokyo , Japan.

This study aimed at determining how cytogenetic risk status affects outcomes for patients with acute myeloid leukemia (AML) after undergoing various types of allogeneic hematopoietic cell transplantation (HCT). Of 7812 patients eligible for analysis, cytogenetic risk was classified as favorable for 1088, intermediate for 5025, and poor for 1699. Overall, multivariate analysis showed significant intergroup differences in terms of relapse and survival, with the difference between poor- and intermediate-risk groups being greater than that between favorable- and intermediate-risk groups. Non-relapse mortality was identical for the three groups. Significant effects of cytogenetic risk status on survival were documented irrespective of donor type (related, unrelated, and umbilical cord blood), disease status at the time of transplantation (first or second complete remission, and more advanced disease status), and conditioning intensity (myeloablative and reduced-intensity). Our findings demonstrate robust and constant effects of cytogenetic risk status on survival after allogeneic HCT for patients with AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2017.1357173DOI Listing
March 2018

Multicenter analysis of transanal tube placement for prevention of anastomotic leak after low anterior resection.

J Surg Oncol 2017 Dec 25;116(8):989-995. Epub 2017 Jul 25.

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Anastomotic leak (AL) is a serious complication of low anterior resection (LAR). This study aimed to evaluate the effect of transanal tube placement for prevention of AL.

Methods: This multicenter retrospective cohort study enrolled 328 consecutive patients who underwent LAR for rectal cancer at participating hospitals from 2009 to 2014. Multivariate logistic regression was used to adjust for confounding factors.

Results: A transanal tube was placed in 205 patients (TA group) and not placed in 123 patients (non-TA group). Symptomatic AL occurred in 36 cases (11%), with significantly higher incidence of symptomatic AL in the non-TA group than in the TA group (15% vs 8.3%, odds ratio [OR] 2.02, 95% confidence interval [CI] 1.01-4.06). After adjusting for confounding factors, multivariate analysis revealed that placement of a transanal tube could decrease the incidence of symptomatic AL (adjusted OR 0.37, 95%CI 0.15-0.91). There was no significant difference in postoperative morbidity, mortality, length of hospital stay, or local recurrence rate between the two groups. Local recurrence rate tended to be higher in patients with symptomatic AL (3/36) than in those without it (10/292).

Conclusions: Transanal tube placement is effective for decreasing the incidence of symptomatic AL after LAR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.24760DOI Listing
December 2017

Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study).

Hematol Oncol 2018 Feb 6;36(1):202-209. Epub 2017 Jul 6.

Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

Complete response (CR) after treatment for multiple myeloma is associated with superior progression-free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto-HCT) between 2010 and 2012. If patients did not achieve CR after auto-HCT, BD consolidation therapy was added to target CR. After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%). After auto-HCT (n = 34), greater than or equal to CR was achieved in 9 patients (20%) and very good partial response (VGPR) was achieved in 11 (24%). Of the 24 patients who received auto-HCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses. Finally, the maximum response with or without BD consolidation was greater than or equal to CR in 19 (41%), VGPR in 7 (15%), and PR in 6 (13%). Through BD consolidation, CR was achieved in 8 of 11 patients with post-HCT VGPR and in 2 of 12 patients with post-HCT PR. In total, 4 year PFS and overall survival were 43 and 80%, respectively. After adjusting for clinical factors, there was no difference in PFS between CR patients after auto-HCT and BD consolidation, while patients with less than or equal to VGPR after consolidation had a significantly lower PFS. Patients with post-HCT CR showed good PFS, and targeting CR through BD consolidation could improve the CR rate. It would be worthwhile to prospectively compare the efficacy of consolidation only for patients who failed to achieve CR to a universal consolidation strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hon.2452DOI Listing
February 2018

Lung adenocarcinoma may be a more susceptive subtype to a dendritic cell-based cancer vaccine than other subtypes of non-small cell lung cancers: a multicenter retrospective analysis.

Cancer Immunol Immunother 2016 09 22;65(9):1099-111. Epub 2016 Jul 22.

R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Objective: The J-SICT DC Vaccine Study Group provides dendritic cell (DC) vaccines for compassionate use under unified cell production and patient treatment regimens. We previously reported beneficial effects of DC vaccines on the overall survival of 62 patients with advanced non-small cell lung cancer (NSCLC) in a single-center analysis. Here, we extended analysis to 260 patients with NSCLC who were treated at six centers.

Methods: Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks.

Results: The mean survival time (MST) from diagnosis was 33.0 months (95 % confidence interval [CI]: 27.9-39.2), and that from time of first vaccination was 13.8 months (95 % CI 11.4-16.8). An erythema reaction at the injection site that was ≥30 mm in diameter was correlated most strongly with overall survival from the first vaccine (≥30 vs. < 30 mm: MST 20.4 vs. 8.8 months, P < 0.001). We reported a similar finding in our previous analysis of patients with advanced pancreatic cancer. Interestingly, although such findings were common between patients with adenocarcinoma and those with other subtypes, the former group experienced significantly prolonged overall survival and a higher response rate for erythema (56.3 vs. 37.3 %, respectively, P = 0.014).

Conclusions: This is the first multicenter study that suggests a possible clinical benefit of DC vaccines for patients with advanced NSCLC, especially those with adenocarcinoma. These findings suggest a specific potential responder population for DC vaccines and warrant further investigation in well-controlled prospective randomized trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-016-1872-zDOI Listing
September 2016

Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation.

J Blood Med 2016 18;7:1-4. Epub 2016 Jan 18.

Department of Hematology and Oncology, Okayama University, Okayama, Japan.

Background: Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood.

Materials And Methods: The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients.

Conclusion: Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JBM.S93008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723029PMC
February 2016
-->