Y Konaka

Tazuke Kofukai Medical Research Institute, Kitano Hospital, Ōsaka, Ōsaka, Japan

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Publications (17)28.56 Total impact

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    ABSTRACT: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune responses, acute phase reactions, and hematopoiesis. In rodent models, IL-6 has been suggested to be one of the essential mediators for optimal acute phase responses to infection and tissue damage. However, in humans, the roles of IL-6 in acute phase responses after surgery remain poorly understood. We present the first case report of successful splenectomy and cholecystectomy in a severe autoimmune-associated hemolytic anemia patient during treatment with a humanized anti-IL-6 receptor antibody. This unique case suggests that IL-6 is not an essential cytokine to safely perform surgical intervention and to prevent postoperative complications and that surgical intervention may not be contraindicated but can be selected as a therapeutic modality in patients treated with anti-IL-6 receptor antibody therapy.
    Langenbeck s Archives of Surgery 06/2008; 393(3):423-5. · 1.89 Impact Factor
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    ABSTRACT: We describe a patient with Wegener granulomatosis (WG) who underwent long-term cyclophosphamide treatment and thereafter developed acute myelogenous leukemia (AML). After the AML was induced into remission, the patient received an allogeneic stem cell transplant (allo-SCT) from his sibling after undergoing a reduced-intensity conditioning regimen. His clinical course shortly after allo-SCT was uneventful. No clinically apparent acute or chronic graft-versus-host disease developed. Repeated analysis of the peripheral blood lymphocytes after transplantation showed complete donor chimerism. The level of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) remained undetectable until 4 months after transplantation, when it began to increase. When the level of PR3-ANCA peaked, the patient suddenly presented with fever and joint pain, which later spontaneously resolved in parallel with the declining titer of PR3-ANCA. He is now in remission for both AML and WG at 22 months after transplantation. The patient's clinical course after allo-SCT may provide us with valuable information regarding the establishment of allo-SCT as a therapeutic option for WG.
    International Journal of Hematology 05/2006; 83(3):262-5. · 1.68 Impact Factor
  • Akane Kunitomi, Yoshiteru Konaka, Masato Yagita
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    ABSTRACT: Hypersensitivity to mosquito bites (HMB) is known to be an allergic reaction and also a skin symptom in some cases of natural killer cell leukemia/lymphoma associated with Epstein-Barr virus (EBV) infection. We describe a patient who had suffered from HMB for 5 years, and subsequently developed mantle cell lymphoma (MCL), which resembled chronic lymphocytic leukemia in the early phase. EBV monoclonality was not detected in lymph nodes by Southern blotting. Serum levels of interleukin-4 and IgE were increased, but they decreased and HMB disappeared when MCL was predominant. We consider that HMB may be a potential sign of MCL.
    Internal Medicine 11/2005; 44(10):1097-9. · 0.97 Impact Factor
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    ABSTRACT: Refractory autoimmune hemolytic anemia (AIHA) is associated with considerable rates of mortality. Interleukin 6 (IL-6) has been reported to play a role in the pathogenesis of AIHA. This report describes a patient with AIHA who was successfully treated with a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody (MoAb). He had experienced life-threatening AIHA and had received conventional therapy with corticosteroids, azathioprine, cyclophosphamide, cyclosporin A, melphalan, plasma exchange, and irradiation to his spleen. However, the patient's symptoms and laboratory data did not show a sufficient improvement. Because his serum IL-6 level was elevated, we attempted to block IL-6 signaling by using a humanized anti-IL-6R MoAb, MRA. With 8 mg/kg of MRA administration every 2 weeks, the serum hemoglobin level gradually increased and normalized within 4 months. After 2 years of MRA treatment, the disease activity was well controlled without adverse reactions. Anti-IL-6R MoAb can be a novel and effective therapeutic agent for AIHA.
    International Journal of Hematology 10/2004; 80(3):246-9. · 1.68 Impact Factor
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    ABSTRACT: We describe a patient with bcr/abl-positive acute mixed lineage leukemia who successfully underwent transplantation in primary induction failure, using unmanipulated bone marrow from a human leukocyte antigen (HLA)-haploidentical cousin. The tumor burden was successfully reduced by the administration of imatinib mesylate (STI571) before transplantation. As graft-versus-host disease (GVHD) prophylaxis, a combination of tacrolimus and a short course of methotrexate, methylprednisolone, and mycophenolate mofetil was used. Hematopoietic reconstitution was rapid, and acute GVHD was limited to the skin (grade I). The patient is still in complete remission past day +400. This successful case suggests that HLA-haploidentical transplantation using unmanipulated marrow from a distantly related relative can be considered for patients in urgent situations who do not have HLA-identical donors.
    Bone Marrow Transplantation 07/2003; 31(12):1165-8. · 3.54 Impact Factor
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    ABSTRACT: To elucidate the differences in pathogenesis between lymphoma-associated hemophagocytic syndromes (LAHS) of the T-cell/ natural killer cell (T/NK) and B-cell (B) types, we comparatively analyzed the clinical features and serum cytokine profiles of 33 patients with LAHS registered in the Kyoto University Hematology/Oncology Study Group. The serum cytokine levels of each patient group (B-LAHS versus T/NK-LAHS) were expressed as the ratio of the median to the upper normal values of the respective cytokines and were as follows: 19.05 versus 13.99 for soluble interleukin 2 (IL-2) receptor, 0.67 versus 0.67 for granulocyte-macrophage colony-stimulating factor (GM-CSF), 0.64 versus 1.26 for G-CSF, 5.70 versus 3.61 for M-CSF, 1.54 versus 3.39 for interferon gamma (IFN-gamma), 13.17 versus 1.17 for IL-6, 6.88 versus 1.58 for tumor necrosis factor alpha (TNF-alpha), 0.71 versus 0.41 for IL-1beta, 1.99 versus 0.21 for IL-12, and 105.32 versus 29.65 for IL-10. The serum levels of IL-6, TNF-alpha, and IL-10 were significantly higher in the B-LAHS group, whereas those of IFN-y were significantly lower. These differences between the 2 groups may reflect a difference in the pathogenesis Higher serum levels of IL-6, TNF-alpha, and IL-10 may be derived at least partly from neoplastic B-cells themselves In addition, the extremely high serum levels of IL-10 suggest that a compensatory anti-inflammatory process may operate in both groups and give rise to a profound immunosuppressive state and a poor outcome.
    International Journal of Hematology 05/2003; 77(3):286-94. · 1.68 Impact Factor
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    ABSTRACT: A multi-center series of 117 patients with malignant lymphoma were analyzed to evaluate the clinical significance of soluble interleukin-2 receptor alpha chain (sIL-2R alpha). The initial levels of sIL-2R alpha ranged from 277 U/ml to 22,800 U/ml with a mean level of 3,451 +/- 4,268 U/ml and a median level of 1,600 U/ml. The sIL-2R alpha levels of the diffuse lymphoma/intermediate-grade subtypes defined by the LSG classification/Working Formulation were higher than those of the follicular lymphoma/low-grade subtypes. There was a tendency for B-cell lymphomas to show higher sIL-2R alpha levels than T-cell lymphomas. The sIL-2R alpha level was correlated with the Ann Arbor clinical stage (I, II versus III, IV), presence or absence of B symptoms, and performance status (0, 1 versus 2, 3, 4) of the patients. The sIL-2R alpha levels were in good accordance with the four risk groups defined by the International Prognostic Indices. Of 21 patients whose tumor burden was serially measured, the coefficients of correlation between sIL-2R alpha and tumor mass were > 0.6 in 18 cases. Sixty-two patients achieved complete remission (CR) during the study; the initial and minimum sIL-2R alpha levels were lower than those of the non-CR patients. This study confirmed that sIL-2R alpha is a convenient and useful marker in the management of malignant lymphoma.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 03/2002; 43(3):170-5.
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    ABSTRACT: We present here a case of aggressive Epstein-Barr virus (EBV)-associated clonal T-cell proliferation with hemophagocytosis that was successfully treated by allogeneic stem cell transplantation using an unrelated donor. A 17-year-old woman was admitted into the hospital with a high fever and liver dysfunction. Laboratory data including bone marrow aspiration revealed hemophagocytic syndrome with proliferation of immature T-lymphoid cells. The clonal proliferation of EBV-infected T cells was confirmed by Southern blot analysis using a terminal-repeat probe from the EBV genome and also by demonstrating T cell-receptor beta gene rearrangement. Intensive immunochemotherapy consisting of cyclosporin A, vincristine, etoposide, and high-dose methylprednisolone did not control the disease and relapse occurred repeatedly. Therefore, during remission after chemotherapy according to the CHOP-E regimen, the patient underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched, unrelated donor. Donor selection was performed with help from the Japanese Association for Marrow Donor Program (JMDP). The patient has remained in good condition without recurrence of disease for 18 months after BMT. Allogeneic BMT is the treatment of choice for aggressive EBV-associated hemophagocytic lymphohistiocytosis even in the case where an HLA-matched sibling donor is not available, especially when the patient is refractory to intensive chemotherapy and/or there is a ready recurrence of disease after conventional therapy.
    International Journal of Hematology 01/2002; 74(4):451-4. · 1.68 Impact Factor
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    ABSTRACT: High-dose therapy with peripheral blood stem cell transplantation (HDT/PBSCT) was performed as one aspect of front-line therapy in patients with poor-risk aggressive non-Hodgkin's lymphoma (high-intermediate/high risk) according to the age-adjusted international prognostic index (aaIPI). Twenty-nine patients were enrolled in this study between November 1994 and March 1999. CHOP + etoposide (CHOP-E) was used as an initial chemotherapy and as a chemotherapy agent for the purpose of cell harvesting. Peripheral blood stem cells were harvested from 17 patients, and HDT with CEC (carboplatin, etoposide, cyclophosphamide)/PBSCT was performed in 11 patients. Eighteen patients dropped out, including five for whom CHOP-E therapy was ineffective and 5 who did not give consent for cell harvesting or HDT/PBSCT. CHOP-E therapy produced complete remission (CR) in 15 out of 26 patients (58%) after discounting the 3 who were ineligible among the 29 who were initially enrolled. The median observation period after PBSCT in the 11 patients who underwent HDT/PBSCT was 25 months (3 to 50 months), and the 3-year disease-free survival rate was 73%. No serious complications associated with the transplantation were observed. We were able to confirm the feasibility and safety of HDT/PBSCT as one form of front-line therapy for aggressive non-Hodgkin's lymphoma in patients under 60 years of age.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 04/2001; 42(3):191-8.
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    ABSTRACT: A 67-year-old man was referred to our hospital for treatment of hemophagocytic syndrome. Hypotension, hypoxemia, pleural effusion, severe anasarca, and splenomegaly were noticed at the time of admission. Laboratory findings showed anemia (7.7 g/dl), thrombocytopenia (4.5 x 10(4)/microliter), an increase of serum LDH (1,466 IU/L) and severe hypoalbuminemia (1.9 g/dl). Bone marrow aspiration revealed an increase of reticulum cells with active hemophagocytosis and the presence of immature lymphocytes (6.0%). Lymphoma was suspected, but effective chemotherapy could not be performed because of progressive hypoxemia and severe hypoalbuminemia, and the patient died of the disease 2 weeks after admission. Autopsy revealed large lymphoid cells packed within systemic vessels as well as invasion into organs such as the liver, lungs, and spleen. The postmortem diagnosis was intravascular large B-cell lymphoma. Hypoalbuminemia and hypoxemia appear to be important clinical features of intravascular large B-cell lymphoma.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 12/2000; 41(11):1189-94.
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    ABSTRACT: We present the establishment of a natural killer (NK) leukemia cell line, designated KHYG-1, from the blood of a patient with aggressive NK leukemia, which both possessed the same p53 point mutation. The immunophenotype of the primary leukemia cells was CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16+, CD56+, CD57+ and HLA-DR+. A new cell line (KHYG-1) was established by culturing peripheral leukemia cells with 100 units of recombinant interleukin (IL)-2. The KHYG-1 cells showed LGL morphology with a large nucleus, coarse chromatin, conspicuous nucleoli, and abundant basophilic cytoplasm with many azurophilic granules. The immunophenotype of KHYG-1 cells was CD1-, CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16-, CD25-, CD33+, CD34-, CD56+, CD57-, CD122+, CD132+, and TdT-. Southern blot analysis of these cells revealed a normal germline configuration for the beta, delta, and gamma chains of the T cell receptor and the immunoglobulin heavy-chain genes. Moreover, the KHYG-1 cells displayed NK cell activity and IL-2-dependent proliferation in vitro, suggesting that they are of NK cell origin. Epstein-Barr virus (EBV) DNA was not detected in KHYG-1 cells by Southern blot analysis with a terminal repeat probe from an EBV genome. A point mutation in exon 7 of the p53 gene was detected in the KHYG-1 cells by PCR/SSCP analysis, and direct sequencing revealed the conversion of C to T at nucleotide 877 in codon 248. The primary leukemia cells also carried the same point mutation. Although the precise role of the p53 point mutation in leukemogenesis remains to be clarified, the establishment of an NK leukemia cell line with a p53 point mutation could be valuable in the study of leukemogenesis.
    Leukemia 06/2000; 14(5):922-30. · 10.16 Impact Factor
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    ABSTRACT: A 41-year-old man was given a diagnosis with of acute promyelocytic leukemia (APL) in August 1994. A chromosome analysis showed 46, XY, t(15; 17) and 47, XY, idem, +8 at that time. Because initial induction chemotherapy (BHAC-DMP) has not been successful, the patient was given 45 mg/m2 of all-trans retinoic acid (ATRA) and achieved complete remission (CR) after 26 days on this regimen. Following intensified chemotherapy, he received an autologous peripheral blood stem cell transplant (PBSCT) with high-dose busulfan and cyclophosphamide in April 1995. Competitive RT-PCR for PML-RAR alpha mRNA did not find any of APL cells in the collected stem-cell fraction. Although the patient remained in CR without therapy, a myeloblastoma was found in his left external auditory canal in August 1996. Recurrence in bone marrow, moreover, was discovered the following month. A chromosome analysis of bone marrow cells showed 47, XY, t(15; 17), +8 at this time. Thus, the extramedullary relapse developed after autologous PBSCT. This case provides information linking ATRA to the development of extramedullary relapse in patients with APL.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 10/1998; 39(9):709-15.
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    ABSTRACT: We report a high risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) in patients receiving oral administration of etoposide for recurrent breast cancer. We examined 119 patients with recurrent disease. Patients were initially treated with anthracyclines, cyclophosphamide, or cisplatin with or without radiation before etoposide treatment. Etoposide was used as the final drug in most cases. Twenty-four patients were treated with the oral administration of etoposide (50 or 100 mg/day for 5-7 days at 4-week intervals). Three cases of t-AML/MDS developed among those 24 patients exposed to etoposide. In contrast, the development of t-AML/MDS was not observed in the other 95 patients not treated with etoposide. Our data suggest that there is a substantial risk of secondary leukemia with oral administration of etoposide for a prolonged period as well as i.v. schedules.
    International Journal of Oncology 08/1998; 13(1):91-6. · 2.66 Impact Factor
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    ABSTRACT: We report a case of Philadelphia (Ph)-positive AML in which interphase fluorescence in situ hybridization (FISH) analysis was performed from diagnosis throughout the course of therapy using major (M-) breakpoint cluster region (BCR)/minor (m-) BCR and ABL cosmid probes. We also investigated the existence of the M-BCR or m-BCR at the RNA or DNA level by the reverse transcriptase polymerase chain reaction and Southern blot analysis, respectively. Complete remission with a normal karyotype was achieved after several regimens of chemotherapy and peripheral blood stem cell transplantation (PBSCT), but relapse occurred and his cells became 100% Ph-positive. We detected the m-BCR/ABL fusion gene by interphase FISH analysis using an m-BCR/ABL translocation probe, and found that FISH analysis was useful for classifying the BCR, identifying minimal residual disease, and for predicting imminent relapse after chemotherapy and PBSCT.
    Leukemia and Lymphoma 07/1997; 26(1-2):185-91. · 2.61 Impact Factor
  • Nihon Naika Gakkai Zasshi 03/1995; 84(2):287-9.
  • Y Konaka, S Namiuchi
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    ABSTRACT: A 47-year-old man presented with fever, cough and chest pain in January, 1989. He was found to have mediastinal tumor and generalized lymphadenopathy. Peripheral blood and bone marrow findings were typical for the chronic phase of chronic myelogenous leukemia (CML). Although the histological findings of a cervical lymph node were indistinguishable from those of malignant lymphoma, cytogenetic studies of the lymph node cells showed positive Ph1 chromosome and rearrangement of the bcr gene as well as bone marrow cells. Double fluorescence analysis of lymph node cells demonstrated co-existence of CD5, CD7 and CD33 positive cells and of cells sharing both CD5 or CD7 and CD33 antigens. These findings suggest that tumor cells originate from the stage at which the differentiation pathways of hematopoietic stem cells branch into precursor T and myeloid cells. Various combination chemotherapies had only partial effects on lymph node swelling. Chronic daily administration of low dose etoposide was very effective to control both lymphadenopathy and leukocytosis and the patient remained well for over 2 years until July, 1991 when hematological myeloid blast crisis developed. He died of pneumonia in October, 1991. This is a rare case of CML with extramedullary mixed crisis which survived for a long time.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 01/1994; 34(12):1556-61.
  • Nihon Naika Gakkai Zasshi 06/1988; 77(5):649-55.