Publications by authors named "Hiroaki Kumagai"

7 Publications

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Reduced dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation.

Bone Marrow Transplant 2021 03 24;56(3):596-604. Epub 2020 Sep 24.

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

Posttransplant cyclophosphamide (PTCy:100 mg/kg) has been increasingly used in allogeneic hematopoietic stem cell transplantation, however, few studies compared different doses of PTCy. We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg/kg of PTCy in 137 patients who underwent HLA-haploidentical peripheral blood stem cell transplantation (haploPBSCT) following reduced-intensity conditioning (RIC). GVHD prophylaxis consisted of PTCy at a dose of 40 mg/kg/day on days 3 and 4, tacrolimus, and mycophenolate mofetil. Neutrophil engraftment was achieved in 97% and 96% in the first and second studies, respectively. The incidences of grades II-IV acute GVHD, III-IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 26%, 5%, 35%, and 18% in the first study, and 23%, 1%, 28%, and 15% in the second study, respectively. Overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 51%, 42%, and 18% in the first study, and 58%, 48%, and 16% in the second study, respectively. The rates of off-immunosuppressants in patients who survived without relapse at 2 years were 83 and 76%. Our results suggest that 80 mg/kg of PTCy is a valid option in haploPBSCT following RIC.
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http://dx.doi.org/10.1038/s41409-020-01065-0DOI Listing
March 2021

Impact of comorbidity and relative dose intensity on outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.

J Cancer Res Clin Oncol 2020 Nov 10;146(11):2995-3002. Epub 2020 Jun 10.

Department of Hematology, Yamagata Prefectural Central Hospital, 1800, Aoyagi, Yamagata, 990-2292, Japan.

Background: Comorbidity and relative dose intensity (RDI) have been associated with survival in diffuse large B-cell lymphoma (DLBCL) patients, but both relationships remain unaddressed in the same patients.

Methods: A retrospective review of consecutive DLBCL patients treated from January 2010 to October 2018 was performed. Data for the clinical characteristics of the patients, including the Charlson Comorbidity Index (CCI) and RDI, on their outcomes were evaluated.

Results: A total of 211 patients with a median age of 72 years (range 19-90 years) were analyzed. CCI ≥ 2 was associated with poor event-free survival (EFS) and overall survival (OS). RDI < 70% was associated with worse EFS and OS. A multivariate analysis revealed that RDI < 70% was only a poor risk factor for the reduction of OS in elderly DLBCL patients (65 years <) and independent from the presence of CCI. The relationship between CCI and RDI in elderly patients was analyzed in four groups, based on CCI ≥ 2 or less and RDI ≥ 70% or less. The group with CCI ≥ 2 and RDI < 70% had a poorer OS and EFS, as compared to the other three groups. The group with CCI < 2 and RDI ≥ 70% had a superior OS but an identical EFS, as compared to the two groups with CCI < 2 and RDI < 70% and CCI ≥ 2 and RDI ≥ 70%.

Conclusions: CCI ≥ 2 was associated with a poorer outcome, but maintaining RDI ≥ 70% may improve the outcome, especially in elderly DLBCL patients.
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http://dx.doi.org/10.1007/s00432-020-03279-7DOI Listing
November 2020

4,4-Diisothiocyanatostilbene Disulfonic Acid Enhanced 15-Deoxy-Δ-prostaglandin J-Induced Neuronal Apoptosis.

Biol Pharm Bull 2019 ;42(11):1913-1920

Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University (HDU).

4,4-Diisothiocyanatostilbene disulfonic acid (DIDS), an antagonist of anion channel including voltage-dependent anion channel (VDAC), acts as both neurotoxicant and neuroprotectant, resulting in the controversy. VDAC contributes to neuronal apoptosis and is a candidate target protein of 15-deoxy-Δ-prostaglandin J (15d-PGJ). Caspase-3 is activated during neuronal apoptosis caused by 15d-PGJ. In the present study, we ascertained whether DIDS was neuroprotective or neurotoxic in the primary culture of rat cortical neurons. Neuronal cell viabilities were primarily evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) reduction assay. Plasma membrane integrity and apoptosis were detected by the staining of propidium iodide (PI) and Hoechst33342, respectively. Alternatively, apoptosis was also measured by caspase-3 assay kit. DIDS did not prevent neurons from undergoing the 15d-PGJ-induced apoptosis. In contrast, DIDS caused neuronal cell death in a concentration-dependent manner by itself, confirming its neurotoxicity. The sublethal application of DIDS did not decrease MTT-reducing activity, increase caspase-3 activity, condense chromatin, allow PI to enter neuron and degenerate neuronal morphology significantly. Interestingly, DIDS enhanced the 15d-PGJ-induced neuronal apoptosis markedly under the sublethal condition. To our knowledge, this is the first report of synergistic effects of DIDS on the neurotoxicity of 15d-PGJ.
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http://dx.doi.org/10.1248/bpb.b19-00536DOI Listing
May 2020

Characterization of reemergent anti-B red blood cell antibodies in a patient with recurrent acute myeloid leukemia with ABO-incompatible allogeneic peripheral blood stem cell transplantation.

Transfusion 2019 11 10;59(11):3319-3323. Epub 2019 Sep 10.

Department of Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan.

Background: Isohemagglutinins against ABO antigens absent on both recipient and donor red blood cells (RBCs) increase or decrease after ABO-incompatible hematopoietic stem cell transplantation (HSCT). However, few reports have described the changes in the isohemagglutinin titers and the characteristics in patients with recurrent hematologic conditions after ABO-incompatible HSCT.

Case Report: A 59-year-old female with acute erythroid leukemia received a peripheral blood stem cell transplant from her HLA-haploidentical daughter. The patient was typed as group O with anti- A (4+) and B (4+) isohemagglutinins, while the donor was typed as group B. The bone marrow cells achieved complete donor cell chimerism on Day 13 after HSCT. On Day 120, the patient showed 97% B RBC type with persistent anti-A (3+) and without anti-B antibodies. On Day 375, her leukemia relapsed, and recipient type O RBCs and anti-B antibodies sequentially reemerged. However, clinicolaboratory hemolysis and erythroid aplasia were not detected in the patient.

Results: The post-HSCT sera agglutinated the allo B RBCs, but not the donor B RBCs, while the pre-HSCT sera agglutinated both RBCs. The burst-forming/colony-forming units of erythroid formation from the donor peripheral blood stem cells were impaired by only the pre-HSCT sera and not by the post-HSCT sera.

Conclusion: To our knowledge, this is the first report investigating the characteristic changes of isohemagglutinins between the pre- and post-HSCT sera in a patient with recurrent acute myeloid leukemia. The present study suggests that the plasma cells producing anti-donor B RBCs in the patient have been selectively eliminated or induced into an anergic state by the post-HSCT immunologic reconstruction.
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http://dx.doi.org/10.1111/trf.15510DOI Listing
November 2019

meningitis in a diffuse large B-cell lymphoma patient with CD4-positive lymphocytopenia and persistent oligoclonal CD8-positive lymphocytes in the peripheral blood.

Int J Clin Exp Pathol 2018 1;11(1):455-461. Epub 2018 Jan 1.

Medical Mycology Research Center, Chiba University Chuo-Ku, Chiba, Japan.

Nocardiosis, sometimes presenting with multiple granulomatous lesions, is a rare opportunistic infection occurring in immunocompromised patients. However, its immunological features remain largely unaddressed. We investigated the immunological characteristics of human nocardiosis and examined the component cells of the granulomatous lesions. A 66-year-old man with diffuse large B-cell lymphoma presented with fever and multiple nodules in the lung during chemotherapy. The blood culture formed white colonies, but their characterization was difficult by routine microbiological laboratory methods. Matrix-assisted laser desorption ionization-time of flight mass spectrometry identified the colonies as . Meanwhile, the patient suddenly experienced an epileptic seizure without a brain abscess. His cerebrospinal fluid (CSF) showed neutrophilic pleocytosis (108/mm). The conventional agar culturing failed to isolate colonies, but culturing with brain-heart infusion agar generated colonies. These colonies were completely concordant with those from the blood, as confirmed by 16S rRNA gene sequencing. Therefore, the patient had developed meningitis through sepsis induced by . His CD4-positive T-lymphocyte counts were low, and oligoclonal CD8-positive αβ T-lymphocytes were present in the blood prior to the first and after three cycles of chemotherapy. He had bone marrow granulomatous lesions comprising lymphoma and CD8-positive αβ T-cells. Treatment with sulfamethoxazole/trimethoprim relieved all of his symptoms. The combined analysis by microbiological and molecular methods determined the cause of his epileptic seizure. His immunological characteristics, including low CD4-positive or CD8-positive αβ T-lymphocytes, may have contributed to the unusual clinical presentations by , which rarely involves the central nervous system.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957946PMC
January 2018

Epstein-Barr virus clonality and plasmacytosis in a patient with atypical angioimmunoblastic T cell lymphoma.

Ann Hematol 2018 Mar 30;97(3):537-539. Epub 2017 Nov 30.

Department of Hematology, Yamagata Prefectural Central Hospital, Yamagata, 990-2292, Japan.

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http://dx.doi.org/10.1007/s00277-017-3189-1DOI Listing
March 2018

[Successful treatment in a case of podostroma cornu-damae poisoning, a deadly poisonous mushroom].

Chudoku Kenkyu 2002 Apr;15(2):177-82

Department of Internal Medicine, Yamagata Prefectural Central Hospital.

Unlabelled: In this case study, a 62-year-old man ate a piece of of Podostroma cornu-damae, poisonous mushroom, by mistake and suffered from severe diarrhea, vomiting and dehydration. The next day he received about 9 liters of solution intravenously over a 12 hour period at his neighboring hospital. The mushroom was identified as Podostroma cornu-damae and he was transported to our hospital on the same day. When he arrived, hypotension due to high capillary permeability accompanied by protein leakage, Leukocytosis, and faint erythema on the body were observed. He was immediately treated by continuous hemodiafiltration (CHDF) and large quantities of solution were given while monitoring the patient's pulmonary capillary wedge pressure and cardiac output. On the seventh day, Leukocytopenia and thrombocytopenia became severe and hemophagocytosis was observed. Plasma exchange (PE) and granulocyte colony stimulating factor (GCSF) were effectively used to treat these hematological disorders. In addition, hypouricemia was also observed, severe depilation occurred, and the skin lesions gradually changed to lameller desquamation. The patient needed over 30 days to recover from leukocytopenia.

Conclusion: It is important to infuse large quantities of solution in the initial treatment of Podostroma cornu-damae poisoning, and blood purification therapy (CHDF and PE) may be highly recommended.
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April 2002
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