Publications by authors named "Osamu Imataki"

126 Publications

Oral microorganisms and bloodstream infection in allogeneic hematopoietic stem cell transplantation.

Clin Oral Investig 2021 Jan 3. Epub 2021 Jan 3.

Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

Objectives: We aimed to compare oral and pathogenic microorganisms in bloodstream infections (BSIs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We also investigated the relationship between BSIs and oral mucositis to identify the ratio of BSIs caused by oral microorganisms and the pathogenic microorganisms involved.

Materials And Methods: We collected data on BSIs in 96 patients who underwent allo-HSCT in our institute between April 2009 and December 2019, including BSI pathogens isolated from blood cultures (BBSIs) and microorganisms isolated from washing the oral cavity with sterile distilled water. Oral microorganisms obtained at the onset of BSI (OBSIs) and during allo-HSCT (OSCTs) were defined as isolates collected during the week of blood culturing. Study entry was limited to samples collected up to 1 month after allo-HSCT without BSI. When the BBSI and OBSI were the same, we considered the oral microorganism to have caused the BSI.

Results: The incidence rate of BSIs was 27%, and the predominant microorganism was coagulase-negative Staphylococci. Normal bacterial flora were decreased to 15.8% in OBSIs and 25.5% in OSCTs. The distribution of microorganisms without normal bacterial flora showed significant difference between BBSIs and OSCTs (p < 0.05). Oral mucositis was found in 72.9%, and BSI caused by oral microorganisms occurred in 46.2% of BSIs in allo-HSCT patients.

Conclusion: The distribution of microorganisms obtained from blood in patients with BSI during allo-HSCT was found to be similar to that of microorganisms from oral cultures.

Clinical Relevance: Oral microorganism monitoring may be able to predict BSI during allo-HSCT.
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http://dx.doi.org/10.1007/s00784-020-03749-9DOI Listing
January 2021

Oncolytic herpes simplex virus type 1 (HSV-1) in combination with lenalidomide for plasma cell neoplasms.

Br J Haematol 2021 01 20;192(2):343-353. Epub 2020 Nov 20.

Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Oncolytic viruses exert an anti-tumour effect through two mechanisms: direct oncolytic and indirect immune-mediated mechanisms. Although oncolytic herpes simplex virus type 1 (HSV-1) has been approved for melanoma treatment and is being examined for its applicability to a broad spectrum of malignancies, it is not known whether it has an anti-myeloma effect. In the present study, we show that the third-generation oncolytic HSV-1, T-01, had a direct oncolytic effect on five of six human myeloma cell lines in vitro. The anti-tumour effect was enhanced in the presence of peripheral blood mononuclear cells (PBMCs) from healthy individuals and, to a lesser extent, from patients with myeloma. The enhancing effect of PBMCs was abrogated by blocking type I interferons (IFNs) or by depleting plasmacytoid dendritic cells (pDCs) or natural killer (NK) cells, suggesting that pDC-derived type I IFNs and NK cells dominated the anti-tumour effect. Furthermore, the combination of T-01 and lenalidomide exhibited enhanced cytotoxicity, and the triple combination of T-01, lenalidomide and IFN-α had a maximal effect. These data indicate that oncolytic HSV-1 represents a viable therapy for plasma cell neoplasms through direct oncolysis and immune activation governed by pDCs and NK cells. Lenalidomide is likely to augment the anti-myeloma effect of HSV-1.
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http://dx.doi.org/10.1111/bjh.17173DOI Listing
January 2021

Oncolytic Virus Therapy with HSV-1 for Hematological Malignancies.

Mol Ther 2021 02 30;29(2):762-774. Epub 2020 Sep 30.

Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan. Electronic address:

Oncolytic herpes simplex virus type 1 (HSV-1) has been investigated to expand its application to various malignancies. Because hematopoietic cells are resistant to HSV-1, its application to hematological malignancies has been rare. Here, we show that the third generation oncolytic HSV-1, T-01, infected and killed 18 of 26 human cell lines and 8 of 15 primary cells derived from various lineages of hematological malignancies. T-01 replicated at low levels in the cell lines. Viral entry and the oncolytic effect were positively correlated with the expression level of nectin-1 and to a lesser extent 3-O-sulfated heparan sulfate, receptors for glycoprotein D of HSV-1, on tumor cells. Transfection of nectin-1 into nectin-1-negative tumor cells made them susceptible to T-01. The oncolytic effects did not appear to correlate with the expression or phosphorylation of antiviral molecules in the cyclic GMP-AMP (cGAS)-stimulator of interferon genes (STING) and PKR-eIF2α pathways. In an immunocompetent mouse model, intratumoral injection of T-01 into lymphoma induced regression of injected, as well as non-injected, contralateral tumors accompanied by abundant infiltration of antigen-specific CD8 T cells. These data suggest that intratumoral injection of oncolytic HSV-1 may be applicable to systemic hematological malignancies. Nectin-1 expression may be the most useful biomarker for optimal efficacy.
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http://dx.doi.org/10.1016/j.ymthe.2020.09.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854286PMC
February 2021

Sea-Blue Histiocytosis of Bone Marrow in a Patient with t(8;22) Acute Myeloid Leukemia.

Case Rep Oncol 2020 May-Aug;13(2):849-852. Epub 2020 Jul 14.

Division of Hematology and Stem Cell Transplantation, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Takamatsu, Japan.

An 80-year-old Japanese male was treated with chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisolone, for non-Hodgkin lymphoma. Nine months after the chemotherapy, he was diagnosed with acute myeloid leukemia (AML) (M4) with translocation 8p11 and 22q13. The patient bone marrow indicated a remarkable degree of sea-blue histiocytosis. His disease was aggressive, and he died of the disease. Sea-blue histiocytes are macrophages harboring blue vacuoles and granular deposition, which results from the phagocytosis of dead cells and the subsequent deposition of phospholipids. AML with the t(8; 22) (p11; q13) translocation is a rare subtype of AML, which is a rare translocation with a prevalence of less than 1.0% among all AML cases. The oncogenesis of t(8; 22) (p11; q13) is caused by the fusion protein monocytic leukemia zinc finger protein (MOZ) and transcription factor p300. MOZ can be fused to various translocation targets including CBT, TIF2, and p300, corresponding to t(8; 16), inv(8), and t(8; 22), respectively. This subgroup of AML reveals the hallmarks of the disease, including monocytic arrest and erythro/hemophagocytosis by blasts. A substantial proportion of the AML M4/M5 subtype harboring MOZ as an aberrant fusion gene represents erythrophagocytosis. Although rare, t(8; 22) is very specific to the AML M4/M5 subtype and seems to represent sea-blue histiocytosis as one of the characteristic features of monocytic AML with macrophage activation. Thus, sea-blue histiocytes are considered to be one of hallmarks in monocytic AML with MOZ translocation.
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http://dx.doi.org/10.1159/000508495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443661PMC
July 2020

A Case of Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia, Chronic Phase with ASXL1 Mutation.

Case Rep Oncol 2020 Jan-Apr;13(1):449-455. Epub 2020 Apr 22.

Division of Hematology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Hematological malignancies, including chronic myeloid leukemia (CML), exhibit mutations; however, the function and molecular mechanism of these mutations remain unclear. was originally identified as tumor suppressor gene, in which loss of function causes myelodysplastic syndrome (MDS). mutations are common and associated with disease progression in myeloid malignancies including MDS, acute myeloid leukemia, and similarly in CML. In MDS, mutations have been associated with poor prognosis; however, the impact of mutations in CML has not been well described. A 31-year-old male was diagnosed as CML-chronic phase (CP). Laboratory findings showed a white blood cell count of 187,200/µL, with asymptomatic splenomegaly. Blast count was 5.0% in peripheral blood and 7.3% in bone marrow. There was no additional chromosomal abnormality except for t(9;22)(q34;q11.2) by chromosomal analysis. At onset, the Sokal score was 1.4, indicating high risk. The patient received tyrosine kinase inhibitor (TKI) therapy, comprising nilotinib ∼600 mg/day, bosutinib ∼600 mg/day, ponatinib ∼45 mg/day, and dasatinib ∼100 mg/day. Nevertheless, after 1.5 years of continuous TKI therapy, the best outcome was a hematological response. Although additional chromosomal aberrations and kinase mutations were analyzed repeatedly before and during TKI therapy, known genetic abnormalities were not detected. Thereafter, the patient underwent bone marrow transplantation from an HLA 7/8 matched unrelated donor (HLA-Cw 1 locus mismatch, graft-versus-host direction). The patient achieved neutrophil engraftment, 18 days after transplantation, leading to complete remission with an undetectable level of mRNA. The patient, however, died from graft-versus-host disease and thrombotic microangiopathy after 121 days. Gene sequence analysis of his CML cell before stem cell transplantation revealed mutations. Physiologically, contributes to epigenetic regulation. In the CML-CP patient in this case report, mutation conferred resistance to TKI through obscure resistance mechanisms. Even though a molecular mechanism for TKI resistance in mutation in CML has remained obscure, epigenetic modulation is a plausible mode of CML disease progression. The clinical impact including prognosis of for CML is underscored. And the treatment strategy of CML with mutation has not been established. A discussion of this case was expected to facilitate treatment options.
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http://dx.doi.org/10.1159/000506452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204851PMC
April 2020

Fatal fulminant hemolysis-associated pulmonary embolism in mixed-type autoimmune hemolytic anemia: A case report.

Medicine (Baltimore) 2020 Feb;99(6):e18984

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University.

Rationale: Autoimmune hemolytic AQ5 anemia (AIHA) is an immune disorder caused by antibodies directed against unmodified autologous red blood cells. In rare cases, AIHA is comorbid with other immunological disorders; for instance, when AIHA is complicated with immunologic thrombocytopenic purpura (ITP) it is called Evans Syndrome (ES). These multiple autoimmune mechanisms are referred to as "immunological tolerance loss," which is known as a characteristic autoimmunity specific for AIHA. And there are no estimation of the risk for thromboembolism in the "immunological tolerance loss" case.

Patient Concerns: A 66-year-old man was diagnosed with ES after autologous stem cell transplantation for malignant lymphoma. His background immunological status was complicated because AIHA was mixed-type (warm and cold antibody type). The direct/indirect Coombs tests were positive. The anticomplement antibody was positive and his cold hemagglutinin level had increased. Anticardiolipin antibodies were negative: anticardiolipin β2GPI antibody ≤1.2 U/mL (<3.5), anticardiolipin immunoglobulin G antibody ≤8 U/mL (<10), and anticardiolipin immunoglobulin M antibody ≤5 U/mL (<8).

Diagnoses: ITP and mixed-type AIHA.

Interventions: The patient achieved complete response by initial prednisolone therapy; however, he did not respond to corticosteroid therapy after AIHA recurrence. He required the red blood cell transfusion due to the progression of hemolytic anemia.

Outcomes: On the fourth day of refractory treatment following AIHA recurrence, the patient had acute respiratory failure with severe hypoxia and died. The cause of death was identified as pulmonary embolism (PE) based on the laboratory data and echocardiography findings, and a literature search suggested rapidly progressive hemolysis-induced PE.

Lessons: Although infrequent, comorbid thromboembolism to AIHA is well documented; however, a mixed-type AIHA case complicated with thromboembolism has not been previously reported. The combined pathophysiology of AIHA and thromboembolism should be considered in the clinical course of hemolysis. Our case suggested multiple immunological background, ITP, and mixed type AIHA, could be associated to a risk for thromboembolism (TE).
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http://dx.doi.org/10.1097/MD.0000000000018984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015575PMC
February 2020

MGUS bone.

Oxf Med Case Reports 2019 Aug 28;2019(8):omz082. Epub 2019 Aug 28.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

A 65-year-old man was referred to our hospital to undergo orthopedic surgery due to severe cervical ossification of the posterior longitudinal ligament. Computed tomography scanning showed a massive osteolytic lesion in his pelvis. Other screening examinations including detection of bone mineral density and osteoporosis biomarkers, bone scintigram and F-fluorodeoxyglucose-positron emission tomography were all normal. Bone marrow aspiration revealed slightly increased plasmacytes at 3.8%. These findings led to a diagnosis of monoclonal gammopathy with undetermined significance (MGUS). Architectural osteolytic bone associated with MGUS without apparent abnormality in bone mineral metabolism could be a common occurrence prior to onset or occurrence of multiple myeloma.
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http://dx.doi.org/10.1093/omcr/omz082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735728PMC
August 2019

Nonclonal chromosomal alterations and poor survival in cytopenic patients without hematological malignancies.

Mol Cytogenet 2019 12;12:46. Epub 2019 Nov 12.

1Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793 Japan.

Background: Clonal chromosomal alterations (CCAs) reflect recurrent genetic changes derived from a single evolving clone, whereas nonclonal chromosomal alterations (NCCAs) comprise a single or nonrecurrent chromosomal abnormality. CCAs and NCCAs in hematopoietic cells have been partially investigated in cytopenic patients without hematological malignancies.

Methods: This single-center retrospective study included 253 consecutive patients who underwent bone marrow aspiration to determine the cause of cytopenia between 2012 and 2015. Patients with hematological malignancies were excluded. CCA was defined as a chromosomal aberration detected in more than two cells, and NCCA was defined as a chromosomal aberration detected in a single cell.

Results: The median age of the patients was 66 years. There were 135 patients without hematological malignancies (median age, 64 years; 69 females); of these, 27 patients (median age, 69 years; 8 females) harbored chromosomal abnormalities. CCAs were detected in 14 patients; the most common CCA was -Y in eight patients, followed by inv.(9) in three patients and mar1+, inv. (12), and t (19;21) in one patient each. NCCAs were detected in 13 patients; the most frequent NCCA was +Y in four patients, followed by del (20), + 8, inv. (2), - 8, and add (6) in one patient each. Moreover, nonclonal translocation abnormalities, including t (9;14), t (14;16), and t (13;21), were observed in three patients. One patient had a complex karyotype in a single cell. The remaining 106 patients with normal karyotypes comprised the control group (median age, 65 years; range, 1-92 years; 56 females). Further, follow-up analysis revealed that the overall survival of the NCCA group was worse than that of the CCA and the normal karyotype groups ( < 0.0001; log-rank test).The survival of the NCCA-harboring cytopenic patients was worse than that of the CCA-harboring cytopenic patients without hematological malignancies, suggesting that follow-up should be considered for both CCA- and NCCA-harboring cytopenic patients.
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http://dx.doi.org/10.1186/s13039-019-0458-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852952PMC
November 2019

Severe rhabdomyolysis associated with severe fever with thrombocytopenia syndrome in a married couple: a case report.

BMC Infect Dis 2019 Oct 24;19(1):885. Epub 2019 Oct 24.

Department of Integrated Medicine, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection that has recently emerged. This infectious disease is due to the transfer of SFTS virus (SFTSV) from the infected blood of animals to humans. Approximately 30% of patients who are infected with SFTS die from multiorgan failure associated with severe infection, systemic inflammatory response syndrome, or disseminated intravascular coagulation. We treated an elderly Japanese couple (husband and wife) who had genetically identical SFTSV infections and who both developed severe rhabdomyolysis.

Case Presentation: An 80-year-old man presented to the clinic with a fever; his 74-year-old wife presented with a fever 9 days later. Their laboratory results at diagnosis showed severe rhabdomyolysis with significantly elevated creatinine kinase (detected levels: husband, 9546 U/L; wife, 15,933 U/L). The creatinine kinase isozyme was 100% MM type in both patients. In both the husband and wife, SFTSV was identified with real-time polymerase chain reaction analysis. The detected SFTSVs in both the husband and wife were identical according to the genome sequence analysis. The husband's bone marrow indicated macrophage activation syndrome, but he responded to supportive therapy. He was discharged after being hospitalized for 32 days. The wife was admitted to our hospital in critical condition 2 days after SFTS symptom onset. She died of multiorgan failure 8 days after onset, despite being cared for in an intensive care unit. Both of the patients presented with rhabdomyolysis following SFTS symptom onset. The patients' clinical outcomes were different from each other; i.e., the husband survived, and the wife died.

Conclusions: SFTSV infection-associated rhabdomyolysis has been reported in one patient, and simultaneous onset in two related patients has not been described previously. Our findings suggest that similar biological responses occurred, but they resulted in different clinical outcomes in the patients infected by the identical SFTSV isolates. Notably, a patient's clinical outcome depends on their own immune response. We suggest that one component of viral rhabdomyolysis involves immune-mediated responses. Severe immunological responses may adversely affect the treatment outcome, as demonstrated by the wife's clinical course. Our findings demonstrate that a patient's immune response contributes to their prognosis following SFTSV infection.
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http://dx.doi.org/10.1186/s12879-019-4535-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813050PMC
October 2019

Effect of ultrasound-guided central venous catheter insertion on the incidence of catheter-related bloodstream infections and mechanical complications.

BMC Infect Dis 2019 Oct 16;19(1):857. Epub 2019 Oct 16.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-town, Kita-county, Kagawa, 761-0793, Japan.

Background: Central venous catheters (CVCs) are necessary for critically ill patients, including those with hematological malignancies. However, CVC insertion is associated with inevitable risks for various adverse events. Whether ultrasound guidance decreases the risk of catheter-related infection remains unclear.

Methods: We observed 395 consecutive CVC insertions between April 2009 and January 2013 in our hematological oncology unit. Because the routine use of ultrasound guidance upon CVC insertion was adopted based on our hospital guidelines implemented after 2012, the research period was divided into before December 2011 (early term) and after January 2012 (late term).

Results: Underlying diseases included hematological malignancies and immunological disorders. In total, 235 and 160 cases were included in the early- and late term groups, respectively. The median insertion duration was 26 days (range, 2-126 days) and 18 days (range, 2-104 days) in the early- and late term groups, respectively. The internal jugular, subclavian, and femoral veins were the sites of 22.6, 40.2, and 25.7% of the insertions in the early term group and 32.3, 16.9, and 25.4% of the insertions in the late term group, respectively. The frequency of catheter-related bloodstream infection (CRBSI) was 1.98/1000 catheter days and 2.17/1000 catheter days in the early- and late term groups, respectively. In the subgroup analysis, the detected causative pathogens of CRBSI did not differ between the two term groups; gram-positive cocci, gram-positive bacilli, and gram-negative bacilli were the causative pathogens in 68.9, 11.5, and 14.8% of the cases in the early term group and in 68.2, 11.4, and 18.2% of the cases in the late term group, respectively. In the multivariate analysis to determine the risk of CRBSI, only age was detected as an independent contributing factor; the indwelling catheter duration was detected as a marginal factor. A significant reduction in mechanical complications was associated with the use of ultrasound guidance.

Conclusions: Ultrasound-guided CVC insertion did not decrease the incidence of CRBSI. The only identified risk factor for CRBSI was age in our cohort. However, we found that the introduction of ultrasound-guided insertion triggered an overall change in safety management with or without the physicians' intent.
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http://dx.doi.org/10.1186/s12879-019-4487-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796423PMC
October 2019

Donor-derived XYY After BMT From a Healthy Volunteer.

Transplantation 2019 10;103(10):e323-e324

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1097/TP.0000000000002861DOI Listing
October 2019

Benefit of Reducing Body Weight Loss with A Nutritional Support Pathway in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Med Sci Monit Basic Res 2019 09 10;25:187-198. Epub 2019 Sep 10.

Division of Stem Cell Transplantation, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan.

Background: This retrospective, historically controlled investigative study examined the benefit of a nutritional support pathway that included nutritional education before the start of conditioning and emphasized oral nutrition in response to nutrition-related adverse events in patients undergoing hematopoietic stem cell transplantation (HSCT).

Material And Methods: Participants were patients undergoing allogeneic HSCT; 46 were in the control group (i.e., did not follow our nutritional pathway) and 36 were in the group that underwent nutritional intervention (enhanced nutrition group). We compared the following parameters between groups from the day before the start of conditioning to the day after completion of parenteral nutrition (PN): percent loss of body weight (%LBW), percent loss of skeletal muscle mass (%LSMM), and estimated basal energy expenditure (EBEE) sufficiency rate. The relationship between each parameter and %LBW was also examined. We also compared nutritional indices, gastrointestinal graft versus host disease (GvHD) grade, oral energy intake, and %LBW between groups.

Results: There was a relationship between %LBW, %LSMM, and EBEE sufficiency rate in both groups. Compared with the control group, the enhanced nutrition group had significantly improved energy intake amount, EBEE sufficiency rate, PN duration, and oral energy intake over time. The enhanced nutrition group also had increased oral energy intake, no difference in gastrointestinal GvHD grade, and improved %LBW compared with the control group.

Conclusions: Use of our nutritional support pathway in patients undergoing HSCT may be beneficial for %LBW and gastrointestinal GvHD grade, enabling early enhanced nutritional intervention after HSCT.
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http://dx.doi.org/10.12659/MSMBR.917329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754707PMC
September 2019

Diagnostic Value of Flow Cytometry Standardized Using the European LeukemiaNet for Myelodysplastic Syndrome.

Acta Haematol 2020 22;143(2):140-145. Epub 2019 Jul 22.

Department of Clinical Laboratory Medicine, Kagawa University, Kagawa, Japan.

Background: Myelodysplastic syndromes (MDS) and idiopathic cytopenia of undetermined significance (ICUS) are heterogeneous hematological disorders characterized by hematopoietic dysplasia and/or chromosomal aberrancy.

Objectives: This study aimed to evaluate the diagnostic value of flow cytometry standardized using the European LeukemiaNet (ELN) for MDS and ICUS by analyzing samples obtained from patients with cytopenia based on morphological examination, cytogenetic analysis, and flow cytometry.

Methods: We retrospectively analyzed bone marrow samples aspirated from 253 consecutive patients (median age: 66 years [range: 1-92]) to identify the cause of cytopenia.

Results: Sixty patients presented with MDS, and 16 with ICUS. MDS subtypes were distributed as follows: MDS with single-lineage dysplasia (n = 10); MDS with multi-lineage dysplasia (n = 10); MDS with ringed sideroblasts (n = 4); MDS with excess blasts-1 (n = 9); MDS with excess blasts-2 (n = 13), MDS unclassified (n = 5); 5q-syndrome (n = 6); and MDS/myeloproliferative neoplasms (n = 3). Four representative ELN indexes were used. Two or more ELN MDS indexes were in the abnormal range in 35 MDS cases (58.3%) and 4 ICUS cases (25.0%).

Conclusions: Morphological examination remains the standard for MDS diagnosis. Considering the low incidence of genetically proven ICUS (20.2-27.5%), the low sensitivity of ELN MDS indexes for ICUS is considered a valuable alternative.
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http://dx.doi.org/10.1159/000501147DOI Listing
April 2020

Graft failure after reduced-intensity stem cell transplantation for congenital sideroblastic anemia.

Pediatr Hematol Oncol 2019 Feb 26;36(1):46-51. Epub 2019 Mar 26.

a Division of Hematology, Department of Internal Medicine, Faculty of Medicine , Kagawa University , Kagawa , Japan.

Congenital sideroblastic anemia (CSA) is a rare hereditary disease causing disorders of hemoglobin synthesis. Severe, progressive congenital sideroblastic anemia becomes transfusion dependent and results in iron overload. In such cases, patients must undergo stem cell transplantation (SCT) before critical organ dysfunction occurs. However, there has been no consensus on the criteria for SCT for congenital sideroblastic anemia. A 17-year-old Japanese boy was newly diagnosed with congenital sideroblastic anemia manifesting dyspnea on effort. His gene analysis revealed ALAS2 R170L. He gradually become dependent on RBC transfusion. Vitamin B6 (pyridoxal, 30 mg/day) therapy and high-dose alpha-linoleic acid supplementation (150 mg/day) had not been effective. We treated the patient with reduced-intensity SCT from a human leukocyte antigen (HLA) alle 8/8-identical unrelated female donor. The preparation regimen applied consisted of cyclophosphamide, fludarabine, total body irradiation (2 Gy), and anti-thymocyte globulin. We experienced secondary graft failure, nevertheless we used enough immunosuppression. Here we discuss the optimal transplantation regimen for an adult-onset congenital sideroblastic anemia patient with transfusion dependency and mild hemosiderosis. We consider a positive indication for SCT in younger (< 20-year-old) patients with congenital sideroblastic anemia with transfusion dependency. Each case should be individually considered for their suitability for SCT depending on the feasibility and the clinical condition of the patient.
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http://dx.doi.org/10.1080/08880018.2019.1578844DOI Listing
February 2019

Lethal cardiac damage resulting from eosinophilia caused by anaplastic large cell lymphoma.

Br J Haematol 2019 05 21;185(4):642. Epub 2019 Feb 21.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1111/bjh.15809DOI Listing
May 2019

Central Nervous System Peripheral T Cell Lymphoma Manifesting as Lymphomatosis Cerebri That Was Misdiagnosed as Neuro-Behçet's Disease: A Case Report.

Case Rep Oncol 2018 Sep-Dec;11(3):806-813. Epub 2018 Nov 29.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Background: Lymphomatosis cerebri (LC) is a unique form of primary central nerves lymphoma (PCNSL), which presents as diffuse infiltration of lymphoma cells characteristically in the white matter rather than tumor formation. However, the involvement of central nervous system (CNS) is unclear because of the lack of contrast enhancement.

Case Presentation: We treated a 53-year-old woman with LC and brain lesions resembling neuro-Behcet's disease. She had a past history of acute uveitis and current symptoms of somnolence and gait disturbances progressing for one month. Cranial magnetic resonance imaging (MRI) revealed high signal lesions in the brain stem. Based on her past history and present clinical findings, she was clinically diagnosed with neuro-Behcet's disease, which was treated with 1 g of methylprednisolone (mPSL) pulse therapy. Repeated mPSL pulse therapy resulted in a minor response, but the cerebral lesions persisted. After a short remission of several months, signal changes of the brain stem lesion recurred and her consciousness level worsened at 4 months after diagnosis. Upon admission to our hospital, positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography revealed abnormal uptake in the systemic lymph nodes (LNs), including the bilateral inguinal LNs. A diagnosis based on a biopsy of the left inguinal LNs was primary central nervous system lymphoma with inguinal LN lesions, manifesting as LC from malignant peripheral T cell lymphoma, not otherwise specified. Four courses of high-dose methotrexate (3.5 g/m) therapy lead to temporary recovery of consciousness, but there was no improvement in other neurological findings. All nodal lesions tentatively regressed. Serum soluble interleukin-2 receptor (sIL-2R) (normal range: 121-613 U/mL) was constitutively decreased from 8,520 U/mL before chemotherapy to 740 U/mL after chemotherapy. We observed cerebral micro-bleeds in the center of LC lesions during chemotherapy, but no surgical intervention was required. Two months later, LC recurred in the brain, which was fatal.

Conclusions: Neuro-Behçet's disease is difficult to distinguish from LC when other clinical findings, including human leukocyte antigen disparity, serum sIL-2R, or cerebrospinal IL-6, are lacking. LC should be differentiated from CNS lymphoma before corticosteroid therapy.
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http://dx.doi.org/10.1159/000495033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323408PMC
November 2018

c-D-index is a risk factor for prolonged febrile neutropenia during chemotherapy in patients with acute myeloid leukemia.

Int J Clin Oncol 2019 May 2;24(5):590-595. Epub 2019 Jan 2.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, Kagawa, 761-0793, Japan.

Background: D-index is a recently established clinical tool for assessing neutropenia severity. This study examined whether the D-index can predict the onset of various infections in patients with febrile neutropenia (FN).

Methods: We retrospectively investigated FN events in consecutive patients aged < 65 years who were treated for newly diagnosed acute myeloid leukemia at our institution. We collected data on all FN events during chemotherapy and evaluated the association of FN severity with infectious events.

Results: This study included 35 patients (18 women and 17 men; median age, 51 years [range 18-65 years]) with 122 FN events. The response rate to induction chemotherapy was 60% (21/35), and all but one patient survived the treatment. The D-index did not predict FN onset. However, in multivariate analysis, high-dose cytarabine and total D-index were statistically significant explanatory factors for microbiological-proven infections. In addition, multivariate analysis showed that diabetes mellitus is the only risk factor for FN onset. Furthermore, older age, consolidation therapy, and cumulative D-index (c-D-index) were risk factors for prolonged FN. The FN period was the longest in patients with respiratory infections.

Conclusion: The D-index did not predict the onset of infection. However, FN duration might be prolonged during consolidation therapy in elderly patients with diabetes mellitus, and it is important to manage respiratory infections. These findings indicate the c-D-index is a useful tool to predict prolonged FN.
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http://dx.doi.org/10.1007/s10147-018-01384-9DOI Listing
May 2019

Small Primary Cutaneous γδT-Cell Lymphoma Lesions Successfully Treated With Pralatrexate.

Clin Nucl Med 2019 Feb;44(2):e85-e86

From the Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Here we report on the treatment of a 38-year-old woman with primary cutaneous γδT-cell lymphoma, which is a rare subset of cutaneous T-cell lymphoma. She presented with multiple subtle subcutaneous nodules, which were not clearly observed on computed tomography scans or after biopsy. However, F-fluorodeoxyglucose positron emission tomography (F-FDG-PET) accurately detected small cutaneous lesions. She achieved a second complete remission, as demonstrated by F-FDG-PET performed after pralatrexate infusion.
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http://dx.doi.org/10.1097/RLU.0000000000002409DOI Listing
February 2019

Asymptomatic hepatosplenomegaly in chronic myeloid leukemia.

Oxf Med Case Reports 2018 Oct 18;2018(10):omy048. Epub 2018 Sep 18.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.

A 39-year-old male diagnosed as chronic myeloid leukemia, had no abdominal symptoms. However, his physical examination revealed apparent abdominal fullness. His liver and spleen were palpable. His abdominal CT revealed that a narrow space to pass intestinal digestive contents. Asymptomatic hepatosplenomegaly is somewhat typical in these chronic type hematological diseases.
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http://dx.doi.org/10.1093/omcr/omy048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142714PMC
October 2018

B-chronic lymphocytic leukemia showed triple transformation, to diffuse large B cell, CD20-negative, and T-cell neoplasm during ofatumumab treatment: a case report.

BMC Clin Pathol 2018 22;18. Epub 2018 May 22.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-town, Kita-county, Kagawa, 761-0793 Japan.

Background: Chronic lymphocytic leukemia (CLL) is a mature lymphoid neoplasm currently categorized as an indolent type of malignant lymphoma. CLL progresses slowly over years, but it eventually transforms to a more aggressive lymphoma such as the diffuse large B-cell (DLBCL) type, also known as Richter's syndrome.

Case Presentation: We treated a 69-year-old Japanese male who was histologically diagnosed with Richter's syndrome after 6 years of CLL. His lymphadenopathy had systemically progressed for years, with lymphocyte counts of less than 10,000 cells/μL and a disease status of Rai classification stage I and Binet classification B. He had high fever and hepatosplenomegaly upon Richter's transformation. The patient was treated with ofatumumab for refractory CLL, which relieved his febrile lymphadenopathy. He received a total of 11 ofatumumab courses and achieved partial remission. On the day of the 12th course of ofatumumab, his disease relapsed with febrile lymphadenopathy. Computed tomography revealed multiple liver masses and systemic lymphadenopathy, while a liver biopsy confirmed T-cell lymphoma. Concomitantly, CD20-lacking CLL cells were detected in his peripheral blood and bone marrow, and pathological examination of his left cervical lymph node biopsy showed CD20-positive DLBCL. The final diagnosis was three different types of lymphoma pathologies: (1) CD20-positive DLBCL of the lymph nodes, (2) CD20-lacking CLL of the peripheral blood and bone marrow, and (3) peripheral T-cell lymphoma (PTCL) of the liver. He received intravenous and oral dexamethasone therapy as palliative care. He died because of the rapid progression of abdominal masses 2 months after the diagnosis of triple transformation CLL. An autopsy revealed aggressive PTCL with aggressive systemic involvement of the liver, spleen, gall bladder, pericardium, bone marrow, and mediastinal-paraaortic-intraceliac lymph nodes. T-cell receptor study of an autopsy specimen supported the diagnosis of PTCL that spread to the intraceliac organs and lymph nodes. We concluded that his pathogenicity progressed to a mixture of triple lymphoma as a result of double malignant transformations, which included PTCL from CLL, CD20-negative CLL, and CD20-positive DLBCL by Richter's transformation.

Conclusions: Our case provides information on the biology of CLL, to transform from a low-grade chemosensitive status to a malignant chemoresistant status.
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http://dx.doi.org/10.1186/s12907-018-0072-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964677PMC
May 2018

Pure erythroid leukemia in a polymyositis patient treated with azathioprine.

Rare Tumors 2018 14;10:2036361318773847. Epub 2018 May 14.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Miki, Japan.

Acute erythroid leukemia, also known as acute myeloid leukemia-M6, may be associated with previous chemotherapy or immunosuppressive therapy. For 10 years, a 69-year-old Japanese female patient with pure erythroid leukemia (or acute myeloid leukemia-M6b) was treated for polymyositis with 50-100 mg/day azathioprine. She complained of dyspnea with low-grade fever and was diagnosed as having pure erythroid leukemia. Chromosomal analysis revealed a complex karyotype abnormality, with the deletion of 5q, -6, -7 and addition of 11q13. No morphological myelodysplastic changes were observed in her bone marrow cells. In this study, azathioprine accumulation was considered to be associated with the patient's leukemogenesis.
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http://dx.doi.org/10.1177/2036361318773847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954579PMC
May 2018

Voriconazole concentration is inversely correlated with corticosteroid usage in immunocompromised patients.

Transpl Infect Dis 2018 Aug 10;20(4):e12886. Epub 2018 Apr 10.

Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan.

Background: Voriconazole (VRCZ) is a broad-spectrum antifungal agent that can be administered both orally and intravenously. A high level of intra- and interindividual variability in serum drug therapeutic concentrations has been reported. We analyzed the influence of corticosteroid use on serum VRCZ concentration by assessing the correlation between corticosteroid dose and VRCZ trough level.

Methods: Immunocompromised patients treated with VRCZ with or without corticosteroid use from June 2010 to March 2017 (6 years and 8 months) were reviewed in our institute. VRCZ and the corticosteroids were administered orally or intravenously. Corticosteroid treatment was considered as "concurrent" only if it was administered within 3 days before or after the initiation of VRCZ. All corticosteroids were converted to a prednisolone-based dosage according to their anti-inflammatory effect (relative glucocorticoid activity). VRCZ concentration was measured at the trough point on the day of steady state.

Results: A total of 85 samples were obtained from 38 patients. The medical records of 23 women and 15 men, with a median age of 61 years (range: 35-86), were reviewed. Twenty-one patients (55.3%, 21/38) received chemotherapy, and 28 (73.7%, 28/38) received corticosteroid therapy. The average and median daily doses of corticosteroids were 59.2 and 89.8 mg, respectively (range: 0.714-377). VRCZ concentration was inversely correlated with corticosteroid dose (r = -.26). The VRCZ concentration was significantly decreased in the corticosteroid user compared to nonuser (P = .013). We evaluated the association of VRCZ concentration and corticosteroid dose in 3 patients among our cohorts for whom more than 5 points of data were available. Intraindividual analysis revealed the trough level of VRCZ concentration decreased as the corticosteroid dose increased. The patients' underlying diseases were hematological diseases (n = 25) and immunological diseases (n = 13). Among accrual patients, no patients were undergoing stem cell transplantation, and no patients were treated with known confounders such as calcineurin inhibitors or phenytoin.

Conclusions: VRCZ might be metabolized by an enzyme induced by corticosteroid treatment; therefore, intraindividual variation in VRCZ metabolism should be considered prior to concurrent treatment, especially for patients with hematological malignancies treated with corticosteroids.
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http://dx.doi.org/10.1111/tid.12886DOI Listing
August 2018

Lemongrass essential oil and citral inhibit Src/Stat3 activity and suppress the proliferation/survival of small-cell lung cancer cells, alone or in combination with chemotherapeutic agents.

Int J Oncol 2018 May 13;52(5):1738-1748. Epub 2018 Mar 13.

Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan.

Small-cell lung cancer (SCLC) is intractable due to its high propensity for relapse. Novel agents are thus needed for SCLC treatment. Lemongrass essential oil (LG-EO) and its major constituent, citral, have been reported to inhibit the proliferation and survival of several types of cancer cells. However, the precise mechanisms through which LG-EO and citral exert their effects on SCLC cells have not been fully elucidated. SCLC cells express Src and have high levels of Src-tyrosine kinase (Src-TK) activity. In most SCLC cell lines, constitutive phosphorylation of Stat3(Y705), which is essential for its activation, has been detected. Src-TK can phosphorylate Stat3(Y705), and activated Stat3 promotes the expression of the anti-apoptotic factors Bcl-xL and Mcl-1. In the present study, LG-EO and citral prevented Src-TK from phosphorylating Stat3(Y705), resulting in decreased Bcl-xL and Mcl-1 expression, in turn suppressing the proliferation/survival of SCLC cells. To confirm these findings, the wild-type-src gene was transfected into the LU135 SCLC cell line (LU135‑wt-src), in which Src and activated phospho-Stat3(Y705) were overexpressed. The suppression of cell proliferation and the induction of apoptosis by treatment with LG-EO or citral were significantly attenuated in the LU135-wt-src cells compared with the control LU135-mock cells. The signal transducer and activator of transcription 3 (Stat3) signaling pathway is also associated with intrinsic drug resistance. LU135-wt-src cells were significantly resistant to conventional chemotherapeutic agents compared with LU135-mock cells. The combined effects of citral and each conventional chemotherapeutic agent on SCLC cells were also evaluated. The combination treatment exerted additive or more prominent effects on LU135-wt-src, LU165 and MN1112 cells, which are relatively chemoresistant SCLC cells. These findings suggest that either LG-EO or citral, alone or in combination with chemotherapeutic agents, may be a novel therapeutic option for SCLC patients.
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http://dx.doi.org/10.3892/ijo.2018.4314DOI Listing
May 2018

Bendamustine and G-CSF support.

Support Care Cancer 2019 05 26;27(5):1581-1582. Epub 2018 Feb 26.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita-county, Miki-town, Kagawa, 761-0793, Japan.

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http://dx.doi.org/10.1007/s00520-018-4118-0DOI Listing
May 2019

Comparison of Nutrition-Related Adverse Events and Clinical Outcomes Between ICE (Ifosfamide, Carboplatin, and Etoposide) and MCEC (Ranimustine, Carboplatin, Etoposide, and Cyclophosphamide) Therapies as Pretreatment for Autologous Peripheral Blood Stem Cell Transplantation in Patients with Malignant Lymphoma.

Med Sci Monit Basic Res 2018 Feb 5;24:31-39. Epub 2018 Feb 5.

Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, Naga-izumi, Shizuoka, Japan.

BACKGROUND The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation. MATERIAL AND METHODS We enrolled patients who underwent autologous peripheral blood stem cell transplantation between 2007 and 2012. Outcomes were compared between ICE therapy (n=14) and MCEC therapy (n=14) in relation to nutrient balance, engraftment day, and length of hospital stay. In both groups, we compared the timing of nutrition-related adverse events with oral caloric intake, analyzed the correlation between length of hospital stay and duration of parenteral nutrition, and investigated the association between oral caloric intake and the proportion of parenteral nutrition energy in total calorie supply. Five-year survival was compared between the groups. RESULTS Compared with the MCEC group, the ICE group showed significant improvement in oral caloric intake, length of hospital stay, and timing of nutrition-related adverse events and oral calorie intake, but a delay in engraftment. Both groups showed a correlation between duration of parenteral nutrition and length of hospital stay (P=0.0001) and between oral caloric intake (P=0.0017) and parenteral nutrition energy sufficiency rate (r=-0.73, P=0.003; r=-0.76, P=0.002). Five-year survival was not significantly different between the groups (P=0.1355). CONCLUSIONS Our findings suggest that compared with MCEC therapy, ICE therapy improves nutrition-related adverse events and reduces hospital stay, conserving medical resources, with no significant improvement in long-term survival. The nutritional pathway may serve as a tool for objective evaluation of pretreatment for autologous peripheral blood stem cell transplantation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810616PMC
http://dx.doi.org/10.12659/msmbr.908113DOI Listing
February 2018

Complete mimicry: a case of alveolar rhabdomyosarcoma masquerading as acute leukemia.

Diagn Pathol 2017 Nov 2;12(1):77. Epub 2017 Nov 2.

Division of Hematology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Background: A small number of rhabdomyosarcoma (RMS) cases involve the bone marrow. A leukemic presentation of RMS has been reported in a few case series, although almost all cases of leukemic RMS are not completely mimicking leukemia. We encountered a case with RMS cell infiltration of the bone marrow that resembled floating hematological cells.

Case Presentation: We encountered a rare case of a 15-year-old boy with a 2-week history of left femoral pain. Upon admission, he was afebrile with no other symptoms. No apparent cause of femoral pain was detected on an initial examination. Laboratory findings revealed normal white blood cell (WBC) count and hemoglobin concentration, with a platelet count of 10.3 × 10/μL. WBCs included 2.0% metamyelocytes, 4.5% myelocytes, and 0.5% blasts. Lactate dehydrogenase concentration was 1299 U/L, creatine kinase was 437 U/L, and C-reactive protein was 1.25 mg/dL. Bone marrow aspiration demonstrated hypercellular marrow (nucleated cell count 1.84 × 10/μL) and 89.0% of blast-like cells of all nucleated cells. The proliferating cells were negative for myeloperoxidase and esterase, and strongly positive for CD56. Positron emission tomography exhibited extensive accumulation of F-fludeoxyglucose with a SUVmax of 7.09. Magnetic resonance imaging revealed T1-low intensity, gadolinium-enhanced, diffuse, and irregular lesions on his pelvis and bilateral femurs. These laboratory and imaging findings suggested hematological malignancy with diffuse bone involvement, suggestive of acute leukemia. However, the pathological diagnosis of bone marrow and basal penile muscle biopsy was alveolar RMS. Karyotype analysis of bone marrow cells revealed the characteristic translocation of t(2;13)(q35;q14). The final diagnosis was alveolar RMS with massive involvement of the bone marrow and the primary site in the perineal muscles. The tumor cells both of the primary site and bone marrow were positive for myogenin.

Conclusions: A literature review found a misdiagnosed case of completely mimicking leukemic RMS as natural-killer (NK)-cell leukemia. Such a misdiagnosis can have critical consequences. We experienced a rare case of alveolar RMS with symmetrical diffuse bone marrow involvement completely masquerading as acute leukemia. The results of a surface marker study showing that the tumor cells had a near NK-cell phenotype were misleading.
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http://dx.doi.org/10.1186/s13000-017-0667-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669030PMC
November 2017

[Fresh Frozen Plasma Provides Endothelial Protection When Administered Early after Stem Cell Transplantation].

Gan To Kagaku Ryoho 2017 Oct;44(10):861-865

Division of Hematology and Stem Cell Transplantation, Faculty of Medicine, Kagawa University.

Background: Veno-occlusive disease(VOD)is a fatal coagulopathy, which is caused by an endothelial disorder among patients who undergo hematopoietic stem cell transplantation(SCT). Some protective agents, such as administration of fresh frozen plasma(FFP), have been evaluated for both prophylactic and targeted therapy.

Purpose: We evaluated the prophylactic efficacy of FFP for VOD in a retrospective study.

Methods: We surveyed patients who received SCT in our hospital between January 2011 and December 2011. We reviewed their data and compared those who were administered prophylactic FFP in the early transplantation period(up to day 60)with those who did not receive prophylactic FFP.

Results: A total of 14 cases were evaluated: 7 female and 7 male, with a median age of 50 years(range of 24 to 63 years). Fibrinogen significantly increased in the FFP group compared with the non-FFP group(p=0.0125). Although the hemostasis parameters of prothrombin time, activated partial thromboplastin time, and D-dimer were all comparable between the 2 groups, the level of fibrinogen degradation products(FDP)was significantly attenuated in the FFP group compared with the non-FFP group(p= 0.0140). Of note, we observed 2 peaks in the D-dimer/FDP ratio in the engraftment period(around day 18)and postengraftment( around day 35)compared with the non-FFP group. Overall survival did not significantly differ between the 2 groups(502 days for FFP, and 586 days for non-FFP, p=0.777).

Discussion: Prophylactic administration of FFP improved hypofibrinogenemia and FDP accumulation in this retrospective analysis of patients who received SCT. We speculate that prophylactic FFP treatment for dyscoagulopathy is effective due to supplementation of coagulation factors. Further study, including randomized trials, is warranted in order to confirm this hypothesis.
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October 2017

Anemia and hypogammaglobulinemia caused by Ménétrier's disease.

Int J Hematol 2018 Jan 12;107(1):3-4. Epub 2017 Oct 12.

Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.

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http://dx.doi.org/10.1007/s12185-017-2349-3DOI Listing
January 2018

A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter retrospective study).

Am J Hematol 2017 Dec 28;92(12):1324-1332. Epub 2017 Sep 28.

Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences. The overall survival (OS) and AML progression-free survival (AML-PFS) of hMDS were higher than those of non-hMDS, especially in patients at age ≥50 and of lower risk in Revised International Prognostic Scoring System (IPSS-R). In competing risks analysis, hMDS exhibited decreased risk of AML-progression in lower IPSS or IPSS-R risk patients, and higher risk of death from BMF in patients at age ≥50. Poor performance status (PS ≥2) and high karyotype risks in IPSS-R (high and very high) were significant risk factors of death and AML-progression in Cox proportional hazards analysis.
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http://dx.doi.org/10.1002/ajh.24905DOI Listing
December 2017