Publications by authors named "Eijiro Omoto"

17 Publications

  • Page 1 of 1

Clarithromycin As an Alternative and Prophylactic Agent in a Hematopoietic Stem Cell Transplantation Patient.

Am J Case Rep 2021 Jun 15;22:e931731. Epub 2021 Jun 15.

Medical Mycology Research Center, Chiba University, Chiba, Japan.

BACKGROUND Nocardia infections have rarely been reported in hematopoietic stem cell transplantation (HSCT) patients, who usually receive the prophylactic use of sulfamethoxazole/trimethoprim (ST) against Pneumocystis jiroveci. However, the ST prophylaxis, sensitive to Nocardia species, sometimes induces renal toxicities. Therefore, alternative prophylactic or therapeutic drugs are required for nocardiosis in HSCT patients. CASE REPORT A 34-year-old Japanese man with acute mixed phenotypic leukemia with t(9; 22) received allogenic peripheral blood HSCT from a haplo-identical sibling donor. He developed graft versus host disease (GVHD) with grade II, and was treated with prednisolone and cyclosporine A with concurrent ciprofloxacin, fluconazole, valacyclovir, and ST. However, the prophylactic ST was ceased because of its renal toxicity. He developed a pulmonary nodular lesion with elevated ß-D-glucan and Aspergillus galactomannan antigen. Repeated blood and sputum culture isolated no pathogens. Voriconazole treatment administered once improved these lesions and laboratory findings. One month later, he presented with right pleuritic chest pain and multiple ring-enhancing cavitation lesions along the ribs. A needle biopsy demonstrated Nocardia elegans, which is an extremely rare infection induced by Nocardia species, in the cavitation lesions, shown by 16S rRNA gene sequencing. He was started on doripenem and liposomal amphotericin B, and a subsequent treatment kept him free from Nocardia elegans infection, without any adverse effects, while continuing the cyclosporine A and prednisolone treatment for chronic GVHD. CONCLUSIONS Clarithromycin has fewer adverse effects than ST. This case suggests that clarithromycin is an appropriate alternative and prophylactic therapy for patients with nocardiosis and ST toxicities.
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http://dx.doi.org/10.12659/AJCR.931731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216568PMC
June 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

Continuous lenalidomide treatment after bortezomib-melphalan-prednisolone therapy for newly diagnosed multiple myeloma.

Ann Hematol 2020 May 4;99(5):1063-1072. Epub 2020 Apr 4.

Higashi Nagoya National Hospital, Nagoya, Japan.

These are the results of phase II study of bortezomib-melphalan-prednisolone (VMP) induction therapy followed by lenalidomide-dexamethasone (Rd) consolidation and lenalidomide maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rates (ORRs), and safety. Eighty-three eligible patients were enrolled between October 2012 and August 2014. The median PFS was 28.0 months (95% CI 19.6-36.7) and the median OS was 55.3 months (95% CI 51.6-NA). Among the patients who received lenalidomide maintenance therapy, median PFS was significantly improved in patients who had achieved a very good partial response (VGPR) or better (41.8 vs 20.7 months, p = 0.0070). As the best response, the rates of partial response or better were 85.5% comprising stringent complete response (sCR, 21.7%), complete response (CR, 10.8%), VGPR (18.1%), and partial response (PR, 34.9%). The most frequently observed grade 3 or higher adverse events during the VMP therapy were anemia (28.9%), neutropenia (15.6%), thrombocytopenia (6.0%), and peripheral neuropathy (2.4%). The most frequently observed grade 3 or higher adverse events during the Rd therapy were anemia (3.5%), neutropenia (1.8%), and skin rush (5.3%). The most frequently observed grade 3 or higher adverse events during lenalidomide maintenance therapy were anemia (7.4%) and neutropenia (24.1%). Thus, VMP induction therapy followed by Rd consolidation and lenalidomide maintenance is considered a well-tolerated and effective regimen in transplant-ineligible NDMM. This trial is registered with UMIN-CTR with the identification number UMIN000009042.
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http://dx.doi.org/10.1007/s00277-020-03988-6DOI 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

Bortezomib-based strategy with autologous stem cell transplantation for newly diagnosed multiple myeloma: a phase II study by the Japan Study Group for Cell Therapy and Transplantation (JSCT-MM12).

Int J Clin Oncol 2019 Aug 1;24(8):966-975. Epub 2019 Apr 1.

Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: The Japan Study Group for Cell Therapy and Transplantation (JSCT) organized a phase II study to evaluate the efficacy and safety of a treatment protocol (JSCT-MM12) for multiple myeloma (MM) patients who were previously untreated and transplantation-eligible. Since bortezomib-based therapy is known to be effective for MM, the protocol is intensified more than the previous protocol (JSCT-MM10) and comprised the subsequent treatments: bortezomib + cyclophosphamide + dexamethasone (VCD) induction; bortezomib + high-dose-melphalan (B-HDM) conditioning with autologous stem cell transplantation (ASCT); bortezomib + thalidomide + dexamethasone (VTD) consolidation; and lenalidomide (LEN) maintenance.

Methods: Sixty-four symptomatic patients aged between 20 and 65 years were enrolled for treatment and received three cycles of VCD, followed by cyclophosphamide administration for autologous stem cell harvest and B-HDM/ASCT, and subsequently two cycles of VTD, after that LEN for 1 year.

Results: Complete response (CR)/stringent CR (sCR) rates for induction, ASCT, consolidation, and maintenance therapies were 20, 39, 52, and 56%, respectively. The grade 3/4 toxicities (≥ 10%) with VCD treatment included neutropenia (27%), anemia (19%), and thrombocytopenia (11%). There was no treatment-related mortality. After median follow-up of 41 months, estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 64% and 88%, respectively. The high-risk group revealed lower CR/sCR, PFS, and OS than the standard-risk group.

Conclusions: The study revealed that the treatment protocol consisting of VCD induction, B-HDM/ASCT followed by VTD consolidation, and LEN maintenance could produce highly beneficial responses and favorable tolerability in newly diagnosed MM. However, future study is required for improving treatment in the high-risk group.
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http://dx.doi.org/10.1007/s10147-019-01436-8DOI Listing
August 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

[Examination of Measures for Preventing Exposure in Nurses Who Handle Cyclophosphamide].

Gan To Kagaku Ryoho 2015 Dec;42(13):2457-9

Dept. of Hospital Pharmacy, Yamagata Prefectural Central Hospital.

Health hazards due to long-term exposure to anticancer drugs have been reported among health care professionals. In Yamagata Prefectural Central Hospital, constant use of personal protective equipment(gloves and mask with face shield)is mandatory, but there is no clear description of the protective gown. To verify the exposure status of nurses while handling cyclophosphamide and the usefulness of a protective gown as a protective measure, urinary concentration of cyclophosphamide was measured for nurses who handled cyclophosphamide. No cyclophosphamide was detected in the urine samples collected from nurses who handled cyclophosphamide while wearing protective gowns or in the samples collected from nurses who handled cyclophosphamide without protective gowns. This finding suggests that gloves and a mask with a face shield are sufficient for preventing exposure to cyclophosphamide. However, considering that only experienced nurses were included as subjects in this study, we cannot conclude that a protective gown is unnecessary, because inexperienced nurses may be exposed to cyclophosphamide. Our study's findings may be one reference to examine measures for preventing exposure in nurses.
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December 2015

An isolated myeloid blast crisis presenting as optic nerve sarcoma in a patient with chronic myeloid leukaemia treated with imatinib.

Br J Haematol 2015 Aug 1;170(3):290. Epub 2015 Jun 1.

Research Centre for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba-shi, Chiba, Japan.

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http://dx.doi.org/10.1111/bjh.13503DOI Listing
August 2015

Hepatic portal venous gas associated with severe graft-versus-host disease of the gastrointestinal tract.

Intern Med 2012 1;51(17):2417-21. Epub 2012 Sep 1.

Department of Hematology, Yamagata Prefectural Central Hospital, Japan.

We report a 67-year-old woman who was diagnosed with hepatic portal venous gas associated with severe graft-versus-host disease (GVHD) of the gastrointestinal tract. The patient received allogenic peripheral blood stem cell transplantation from a haploidentical son against Philadelphia chromosome-positive acute lymphocytic leukemia. The patient developed grade 3 intestinal GVHD on day 90 from the transplantation. On day 149, she presented septic shock and computed tomography (CT) scan revealed hepatic portal venous gas (HPVG); an ileocecal resection was performed immediately. The damage of gastrointestinal mucosa by GVHD resulted in the invasion of gas-producing bacteria. Although HPVG-associated gastrointestinal GVHD is extremely rare, we should pay special attention to this pathogenesis.
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http://dx.doi.org/10.2169/internalmedicine.51.7419DOI Listing
April 2013

[Sequential monitoring of plasma EBV-DNA level in a patient with EBV-positive Hodgkin lymphoma].

Rinsho Ketsueki 2012 Jan;53(1):87-91

Department of Hematology, Tokyo Medical and Dental University Hospital.

A 58-year-old woman was admitted to our hospital because of fever, systemic lymphadenopathy with abnormal Epstein-Barr virus (EBV) antibody titers, and a high EBV-DNA load in the serum. She had been diagnosed as possibly having chronic active EBV infection (CAEBV) during a previous hospitalization. The EBV-DNA load of the plasma (pEBV-DNA), examined at our hospital, was elevated to 1.8×10(4) copies/ml, whereas that of the peripheral blood mononuclear cells was 3.4×10(1) copies/μg DNA, which was not clearly elevated, unlike in cases with CAEBV. Biopsy of the cervical lymph node was performed and the diagnosis of mixed cellularity classical Hodgkin lymphoma, Stage4B was made. Hodgkin cells were positive for EBV. COPP therapy was started and pEBV-DNA decreased drastically. The treatment was followed by ABVD therapy and pEBV-DNA turned negative after one course of ABVD therapy. She achieved complete response after 4 courses of the treatment. Reports from abroad indicate that pEBV-DNA parallels the disease state of EBV-positive Hodgkin lymphoma. Our results were consistent with these reports, and demonstrated that, in a Japanese patient, EBV-DNA load and its localization in the peripheral blood fractions could be useful tools for diagnosis as well as evaluating the disease status.
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January 2012

Fournier's gangrene in a patient receiving treatment for idiopathic thrombocytopenic purpura.

Intern Med 2011 15;50(18):2015-9. Epub 2011 Sep 15.

Department of Hematology, Yamagata Prefectural Central Hospital, Japan.

We report the case of a 68-year-old man who was diagnosed with Fournier's gangrene (FG), which developed during immunosuppresive treatment for idiopathic thrombocytopenic purpura (ITP). The patient was administered steroids for ITP but on the 36th day, he developed FG and septic shock. We initiated antibiotic treatment and drained a periproctal abscess immediately. On day 53, extensive drainage to progressive FG and a splenectomy was performed, following which both FG and thrombocytopenia improved. This is the first case of FG has developing in a ITP patient. It appears that high-dose immunoglobulin therapy and splenectomy should be considered earlier especially for a patient complicated with FG.
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http://dx.doi.org/10.2169/internalmedicine.50.5323DOI Listing
January 2012

[Case report: a case of cholesterol crystal embolism mimicking vasculitis].

Nihon Naika Gakkai Zasshi 2011 Aug;100(8):2247-9

Department of Internal Medicine, Yamagata Prefecutural Central Hospital, Japan.

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http://dx.doi.org/10.2169/naika.100.2247DOI Listing
August 2011

Disseminated Mycobacterium genavense infection in a healthy boy.

Hum Pathol 2010 Nov 22;41(11):1646-9. Epub 2010 Jul 22.

Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata 990-2292, Japan.

Mycobacterium genavense (M genavense) has been recognized as a life-threatening pathogen in severely immunocompromised patients. To our knowledge, disseminated M genavense infection has never been described in immunocompetent individuals. Here, we report a case of disseminated M genavense infection in a healthy Japanese boy. A 15-year-old boy who had never been diagnosed with an immunodeficiency disorder was hospitalized because of ileus. Tumorous lesions were identified in the ileum, cecum, and ascending colon, resulting in stenosis of ileocecal valve. There was diffuse proliferation of histiocytes throughout the intestinal wall, along with lymphocytic infiltration. No nuclear or cellular atypia was present in these cells. Ziehl-Neelsen staining revealed numerous acid-fast bacteria in histiocytes. After surgery, systemic lymph node swelling was noticed by generalized examination, including the mesenteric and cervical lymph nodes. M genavense DNA was identified by direct sequencing of 16S ribosomal DNA that had been amplified by polymerase chain reaction.
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http://dx.doi.org/10.1016/j.humpath.2010.02.017DOI Listing
November 2010

[Serum free light-chain assay for nonsecretory multiple myeloma with light chain cast nephropathy and light chain deposition disease].

Rinsho Ketsueki 2010 Apr;51(4):270-4

Department of Medicine, Yamagata Prefectural Central Hospital.

Quantitative assay for serum free light chains (sFLC) is reported as a useful test for diagnosis and monitoring of patients with nonsecretory multiple myeloma (NSM). We performed serial sFLC assays in a patient with NSM with light chain cast nephropathy (LCCN) and light chain deposition disease (LCDD). After 3 cycles of VAD induction therapy, while plasma cells in the marrow decreased from 93.0% to 0.2%, sFLCkappa/lambda ratio remained abnormal. Flow cytometry assay also showed that these plasma cells were CD19 negative. After the subsequent high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation (PBSCT), the sFLCkappa/lambda ratio returned to normal and the patient achieved a stringent complete response (sCR). One year after PBSCT, the patient remained in sCR with improved renal function. The quantitative FLC assay was useful for the diagnosis and monitoring of NSM and LCDD in this patient.
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April 2010

Cerebrovascular disease in acute leukemia: a clinicopathological study of 14 patients.

Intern Med 2002 Dec;41(12):1130-4

Third Department of Internal Medicine, Yamagata University School of Medicine, Yamagata.

Objective: Cerebrovascular disease (CVD) is a serious complication of acute leukemia, and the underlying conditions are different from the common risk factors for CVD. The aim of this study was to characterize the clinical and pathological features of CVD in patients with acute leukemia.

Patients Or Materials: In our series of 116 autopsied cases of acute leukemia during the period between January 1978 and December 1998, we had 14 patients who had CVD during the course of acute leukemia. The neuropathological and clinical features of those patients were examined.

Results: Neuropathological examination showed hemorrhagic infarction due to disseminated aspergillosis or mucormycosis (5 cases), multiple hemorrhages due to leukemic cell infiltration (2 cases) and a single massive hemorrhage with petechial hemorrhages in various regions of the brain (4 cases). Three patients had CVD due to miscellaneous causes. Clinicopathological correlation revealed that fungal disseminations occurred under agranulocytosis, while leukemic cell infiltration occurred under a marked leukocyotosis (peripheral white blood cell count >100,000/microl). Four patients with coagulopathy, including three with disseminated intravascular coagulation (DIC) had a single massive hemorrhage.

Conclusion: Our study demonstrated that there were at least three types of CVD with specific clinicopathological features. Hemorrhagic infarction under agranulocyotosis was due to disseminated aspergillosis or mucormycosis. Multiple cerebral hemorrhages under marked leukocyotosis was due to leukemic cell infiltration into the brain. Massive cerebral hemorrhage was associated with coagulopathy including DIC.
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http://dx.doi.org/10.2169/internalmedicine.41.1130DOI Listing
December 2002
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