Publications by authors named "Kana Miyazaki"

34 Publications

Early central nervous system relapse of monomorphic epitheliotropic intestinal T-cell lymphoma after cord blood transplantation.

Int J Hematol 2021 Jul 1;114(1):129-135. Epub 2021 Mar 1.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare subtype of intestinal T-cell lymphoma that occurs mostly in Asia. CHOP-like therapy is usually selected, but the prognosis is very poor. This report concerns a 43-year-old woman with newly diagnosed stage IVA MEITL. The patient obtained a partial response after 4 cycles of GDP (gemcitabine, dexamethasone, cisplatin) and achieved a complete response (CR) after cord blood transplantation (CBT) conditioned with total body irradiation, cyclophosphamide, and cytarabine. Seven months after transplantation, the patient experienced cognitive impairment. Magnetic resonance imaging of the brain showed a high-intensity lesion in the right cerebral peduncle and internal capsule. A cerebrospinal fluid examination confirmed central nervous system (CNS) relapse of MEITL. After 3 cycles of MPV (methotrexate, procarbazine, vincristine) followed by whole-brain radiotherapy, her cognitive impairment improved. Due to disease progression, she died 6 months after CNS relapse. Given the CNS relapse after achieving a CR with GDP and CBT in this patient, CNS prophylaxis during first-line therapy may be beneficial in the treatment of MEITL.
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http://dx.doi.org/10.1007/s12185-021-03107-9DOI Listing
July 2021

A randomized phase 2/3 study of R-CHOP vs CHOP combined with dose-dense rituximab for DLBCL: the JCOG0601 trial.

Blood Adv 2021 02;5(4):984-993

Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) is the standard of care for untreated diffuse large B-cell lymphoma (DLBCL). However, the schedule for rituximab administration has not been optimized. To compare standard R-CHOP with CHOP plus dose-dense weekly rituximab (RW-CHOP) in patients with untreated DLBCL, we conducted a phase 2/3 study (JCOG0601, jRCTs031180139). Patients were randomly assigned to R-CHOP (CHOP-21 with 8 doses of rituximab once every 3 weeks [375 mg/m2]) or RW-CHOP (CHOP-21 with 8 doses of weekly rituximab [375 mg/m2]) groups. The primary end point of the phase 2 component was percent complete response (%CR) of the RW-CHOP arm, whereas that of the phase 3 component was progression-free survival (PFS). Between December 2007 and December 2014, 421 untreated patients were randomly assigned to R-CHOP (213 patients) or RW-CHOP (208 patients). The %CR in the RW-CHOP arm was 85.3% and therefore met the prespecified decision criteria for the phase 2 component. With a median follow-up of 63.4 months, the 3-year PFS and overall survival were 79.2% and 88.7% in the R-CHOP arm and 80.3% and 90.4% in the RW-CHOP arm, respectively. There was no significant difference in PFS (hazard ratio, 0.95; 90.6% confidence interval, 0.68-1.31). Although the safety profile and efficacy of RW-CHOP was comparable with R-CHOP and its tolerability was acceptable, weekly rituximab in combination with CHOP during the early treatment period did not improve PFS in untreated patients with DLBCL. This trial was registered at jrct.niph.go.jp as #jRCTs031180139.
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http://dx.doi.org/10.1182/bloodadvances.2020002567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903239PMC
February 2021

DA-EPOCH-R combined with high-dose methotrexate in patients with newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma: a single-arm, open-label, phase II study.

Haematologica 2020 09 1;105(9):2308-2315. Epub 2020 Sep 1.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie.

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by poor prognosis and a high frequency of central nervous system relapse after standard immunochemotherapy. We conducted a phase II study to investigate the efficacy and safety of dose-adjusted (DA)- EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) combined with high-dose methotrexate (HD-MTX) in newly diagnosed patients with CD5+ DLBCL. Previously untreated patients with stage II to IV CD5+ DLBCL according to the 2008 World Health Organization classification were eligible. Four cycles of DA-EPOCH-R followed by two cycles of HD-MTX and four additional cycles of DAEPOCH- R (DA-EPOCH-R/HD-MTX) were planned as the protocol treatment. The primary end point was 2-year progression-free survival (PFS). Between September 25, 2012, and November 11, 2015, we enrolled 47 evaluable patients. Forty-five (96%) patients completed the protocol treatment. There were no deviations or violations in the DA-EPOCH-R dose levels. The complete response rate was 91%, and the overall response rate was 94%. At a median follow up of 3.1 years (range, 2.0-4.9 years), the 2- year PFS was 79% [95% confidence interval (CI): 64-88]. The 2-year overall survival was 89% (95%CI: 76-95). Toxicity included grade 4 neutropenia in 46 (98%) patients, grade 4 thrombocytopenia 12 (26%) patients, and febrile neutropenia in 31 (66%) patients. No treatment-related death was noted during the study. DA-EPOCH-R/HD-MTX might be a first-line therapy option for stage II-IV CD5+ DLBCL and warrants further investigation. (Trial registered at: UMIN-CTR: UMIN000008507.).
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http://dx.doi.org/10.3324/haematol.2019.231076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556618PMC
September 2020

Dose-adjusted EPOCH with or without rituximab for aggressive lymphoma patients: real world data.

Int J Hematol 2020 Dec 3;112(6):807-816. Epub 2020 Sep 3.

Innovative Cancer Center/Oncology-Hematology, Shimane University Hospital, 89-1 Enya, Izumo, Shimane, 693-8501, Japan.

CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) -/+ rituximab (R) is the standard chemotherapeutic regimen for aggressive lymphoma, but is insufficient for aggressive lymphoma with adverse prognostic factors. Dose-adjusted (DA)-EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisolone) -/+ R demonstrates excellent efficacy against some aggressive lymphoma. Thus, we conducted a retrospective study to evaluate the feasibility and efficacy of this therapy in clinical practice. We enrolled 149 patients from 17 institutions diagnosed between 2007 and 2015. The median follow-up period for survivors was 27 months (range 0.2-123). The complete response (CR) rate of newly diagnosed patients was 79% (95% CI 68-87%). All patients were hospitalized to receive this therapy and 94% of patients also received granulocyte-colony-stimulating factor support. There were no treatment-related deaths. Febrile neutropenia (FN) and grade 3 or 4 infection occurred in 55% and 28% of patients, respectively. There were no significant differences in FN or infection between young (≤ 65 years) and elderly patients (> 65 years). In newly diagnosed diffuse large B-cell lymphoma-not otherwise specified patients (n = 46), the CR rate was 80% (95% CI 64-91%) and the 2-year OS rate was 81% (95% CI 66-90%). In the present study, DA-EPOCH -/+ R exhibited excellent efficacy and feasibility for aggressive lymphoma.
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http://dx.doi.org/10.1007/s12185-020-02984-wDOI Listing
December 2020

Prediction and prevention of central nervous system relapse in patients with extranodal natural killer/T-cell lymphoma.

Blood 2020 11;136(22):2548-2556

Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Because non-anthracycline-based chemotherapy with l-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with that in previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose methotrexate (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into 2 groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m2. A new central nervous system-prognostic index of natural killer (CNS-PINK) model was developed using 1-point powerful predictors of CNS relapse (PINK; hazard ratio [HR], 2.908; P = .030 and extranodal involvement [≥2]; HR, 4.161; P = .001) and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation (P = .038) cohorts. Patients in the high-risk CNS-PINK group who were treated with SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effectiveness of S-ID-MTX in preventing CNS events in high-risk CNS-PINK patients should be verified in future studies.
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http://dx.doi.org/10.1182/blood.2020005026DOI Listing
November 2020

Randomised phase II study to optimise melphalan, prednisolone, and bortezomib in untreated multiple myeloma (JCOG1105).

Br J Haematol 2021 02 24;192(3):531-541. Epub 2020 Jun 24.

Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.

We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant-ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six-week cycle followed by eight five-week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1-4) or Arm B (nine four-week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1-4). The primary end-point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45·8 and 35·1 mg/m , CR rate was 18·6% [95% confidence interval (CI) 8·4-33·4] and 6·7% (95% CI 1·4-18·3), and the median progression-free survival (PFS) was 2·5 and 1·4 years in Arms A and B [hazard ratio (HR) 1·93 (95% CI 1·09-3·42)], respectively. Frequent grade ≥3 haematologic toxicities in Arms A and B were neutropenia (64·4% vs. 28·3%) and thrombocytopenia (35·6% vs. 10·9%). Grade 2/3 peripheral neuropathy was observed in 24·4/2·2% in Arm A and 8·7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB.
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http://dx.doi.org/10.1111/bjh.16878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891591PMC
February 2021

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): a multicentre, single-arm, phase 2 trial.

Lancet Oncol 2020 04 11;21(4):593-602. Epub 2020 Mar 11.

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

Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. We aimed to ascertain the safety and activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) with high-dose methotrexate and intrathecal chemotherapy as CNS-oriented therapy for patients with previously untreated IVLBCL.

Methods: PRIMEUR-IVL is a multicentre, single-arm, phase 2 trial at 22 hospitals in Japan. Eligible patients had untreated histologically confirmed IVLBCL, were aged 20-79 years, had an Eastern Cooperative Group performance status of 0-3, and had no apparent CNS involvement at diagnosis. Patients received three cycles of R-CHOP (rituximab 375 mg/m intravenously on day 1 [except cycle one, which was on day 8]; cyclophosphamide 750 mg/m, doxorubicin 50 mg/m, and vincristine 1·4 mg/m [maximum 2·0 mg] intravenously on day 1 of cycle one and day 2 of cycles two and three; and prednisolone 100 mg/day orally on days 1-5 of cycle one and days 2-6 of cycles two and three) followed by two cycles of rituximab with high-dose methotrexate (3·5 g/m intravenously on day 2 of cycles four and five) every 2 weeks and three additional cycles of R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) was administered four times during the R-CHOP phase. The primary endpoint was 2-year progression-free survival. Efficacy analyses were done in all enrolled patients; safety analyses were done in all enrolled and treated patients. The trial is registered in the UMIN Clinical Trials Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165); the trial is ongoing for long-term follow-up.

Findings: Between June 16, 2011, and July 21, 2016, 38 patients were enrolled, of whom 37 were eligible; one patient was excluded because of a history of testicular lymphoma. Median follow-up was 3·9 years (IQR 2·5-5·5). 2-year progression-free survival was 76% (95% CI 58-87). The most frequent adverse events of grade 3-4 were neutropenia and leucocytopenia, which were reported in all 38 (100%) patients. Serious adverse events were hypokalaemia, febrile neutropenia with hypotension, hypertension, and intracerebral haemorrhage (reported in one [3%] patient each). No treatment-related deaths occurred during protocol treatment.

Interpretation: R-CHOP combined with rituximab and high-dose methotrexate plus intrathecal chemotherapy is a safe and active treatment for patients with IVLBCL without apparent CNS involvement at diagnosis, and this regimen warrants future investigation.

Funding: The Japan Agency for Medical Research and Development, the Center for Supporting Hematology-Oncology Trials, and the National Cancer Center.
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http://dx.doi.org/10.1016/S1470-2045(20)30059-0DOI Listing
April 2020

Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy.

Int J Hematol 2020 May 28;111(5):686-691. Epub 2020 Jan 28.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common and life-long toxicity in lymphoma patients receiving current standard chemotherapy. The association between VIPN and genetic polymorphisms is largely unknown in adult lymphoma patients. To examine the possible relationship between known genetic polymorphisms in patients with pediatric acute lymphoblastic leukemia and incidence of VIPN in adult patients with B cell lymphoma, we examined CEP72 rs924607, ETAA1 rs17032980, MTNR1B rs12786200, CYP3A5 rs776746, rs7963521, and rs1045644 genetic polymorphisms in samples from 56 adult patients with B-cell lymphoma who received rituximab, cyclophosphamide, doxorubicin, VCR, and prednisone (R-CHOP) chemotherapy. Mutation analysis was performed by direct sequencing. The median age was 65 years (range 30-79). The median cumulative dose of VCR was 12 mg (range 2-16). VIPN was documented in 42 patients (75%), and 9 (16%) had grade 2-4 VIPN. Age, impaired glucose tolerance, number of cycles of R-CHOP, and VCR cumulative dose were not associated with incidence of VIPN. There was no association between the incidence of grade 2-4 or any grade VIPN and these six genetic polymorphisms. These results indicate that CEP72, MTNR1B, ETAA1, CYP3A5, rs7963521, and rs1045644 genetic polymorphisms are not associated with VIPN in patients with B-cell lymphoma who received R-CHOP.
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http://dx.doi.org/10.1007/s12185-020-02832-xDOI Listing
May 2020

Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin.

Ann Hematol 2019 Jul 19;98(7):1647-1655. Epub 2019 Apr 19.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.
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http://dx.doi.org/10.1007/s00277-019-03689-9DOI Listing
July 2019

R-High-CHOP/CHASER/LEED with autologous stem cell transplantation in newly diagnosed mantle cell lymphoma: JCOG0406 STUDY.

Cancer Sci 2018 Sep 28;109(9):2830-2840. Epub 2018 Jul 28.

Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.

Although induction immunochemotherapy including high-dose cytarabine and rituximab followed by high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) is recommended for younger patients (≤65 years old) with untreated mantle cell lymphoma (MCL), no standard induction and HDC regimen has been established. We conducted a phase II study of induction immunochemotherapy of R-High-CHOP/CHASER followed by HDC of LEED with ASCT in younger patients with untreated advanced MCL. Eligibility criteria included untreated MCL, stage II bulky to IV, and age 20-65 years. Patients received 1 cycle of R-High-CHOP followed by 3 cycles of CHASER every 3 weeks. Peripheral blood stem cells (PBSC) were harvested during CHASER. LEED with ASCT was delivered to patients who responded to R-High-CHOP/CHASER. Primary endpoint was 2-year progression-free survival (PFS). From June 2008 to June 2012, 45 patients (median age 59 years; range 38-65 years) were enrolled. PBSC were successfully harvested from 36 of 43 patients. Thirty-five patients completed ASCT. Two-year PFS was 77% (80% CI 68-84), which met the primary endpoint. Five-year PFS and overall survival were 52% (95% CI 34-68%) and 71% (95% CI 51-84%), respectively. Overall response and complete response rates after induction immunochemotherapy were 96% and 82%, respectively. The most common grade 4 toxicities were hematological. In younger patients with untreated MCL, R-High-CHOP/CHASER/LEED with ASCT showed high efficacy and acceptable toxicity, and it can now be considered a standard treatment option.
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http://dx.doi.org/10.1111/cas.13719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125440PMC
September 2018

Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Cancer Sci 2018 Jun 28;109(6):2056-2062. Epub 2018 Apr 28.

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

Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs.
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http://dx.doi.org/10.1111/cas.13597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989836PMC
June 2018

[Atypical hemolytic uremic syndrome with C3 p.I1157T missense mutation successfully treated with eculizumab].

Rinsho Ketsueki 2018;59(2):178-181

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

A 23-year-old man from Mie Prefecture, Japan, with past and family history of hematuria was diagnosed with influenza A and admitted to our hospital on the following day because of hemoglobinuria. He was diagnosed with thrombotic microangiopathy and was suspected of having atypical hemolytic uremic syndrome (aHUS). C3 p.I1157T missense mutation, which we had previously reported in eight aHUS patients from six families in Mie Prefecture, was identified. The laboratory findings and symptoms of our patient promptly improved after administering eculizumab. Little information is available on abnormalities of the complement system in aHUS or on mutation-specific outcomes of eculizumab therapy. Eculizumab was effective for treating our aHUS patient with C3 p.I1157T missense mutation.
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http://dx.doi.org/10.11406/rinketsu.59.178DOI Listing
February 2019

Isolated thrombocytosis in chronic myeloid leukemia without significant leukocytosis.

Rinsho Ketsueki 2017 ;58(7):766-771

Department of Hematology and Oncology, Mie University Hospital.

Chronic myeloid leukemia (CML) typically causes leukocytosis rather than thrombocytosis. We encountered two women in their thirties with remarkable thrombocytosis, whose platelet counts were over 3,000×10/µl, and without significant leukocytosis. Although their clinical findings resembled that of essential thrombocythemia (ET), they were diagnosed with CML because of the presence of Philadelphia chromosome. JAK2, CALR, and MPL were unmutated. On fluorescence in situ hybridization analysis, only 19.8% of granulocytes in case 2 were found to be BCR/ABL positive in peripheral blood (PB). We reviewed 11 CML cases whose platelet counts were over 2,000×10/µl, but their WBC counts were not significantly elevated (<12,000/µl). Most of them were young females with a normal or a high neutrophil alkaline phosphatase score and without immature myeloid cells in PB. These findings suggested that there is a subgroup of CML patients with marked thrombocytosis and without significant leukocytosis, which may be misdiagnosed as ET.
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http://dx.doi.org/10.11406/rinketsu.58.766DOI Listing
December 2017

Current treatment approaches for NK/T-cell lymphoma.

J Clin Exp Hematop 2017 Dec 6;57(3):98-108. Epub 2017 Jul 6.

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a form of lymphoma characterized by preferential extranodal involvement, Epstein-Barr virus (EBV) association, and geographic diversity in incidence. ENKL tumor cells express P-glycoprotein, which is related to multidrug resistance (MDR). This MDR phenomenon is thought to be the major reason why ENKL is resistant to anthracycline-containing chemotherapies and has led researchers to explore novel therapeutic strategies. Since the early 2000s, next-generation therapies, including upfront radiotherapy, chemotherapy, or concurrent chemoradiotherapy using non-MDR-related drugs, have markedly changed the management of ENKL. However, a recent large retrospective study in Japan revealed several limitations of next-generation therapies, in particular that they resulted in almost no improvement of early disease progression. This review will summarize the current management of ENKL, primarily based on clinical trial results, and provide clues for better future management.
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http://dx.doi.org/10.3960/jslrt.17018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144191PMC
December 2017

Management of Pulmonary Mucormycosis Based on a Polymerase Chain Reaction (PCR) Diagnosis in Patients with Hematologic Malignancies: A Report of Four Cases.

Intern Med 2017 17;56(6):707-711. Epub 2017 Mar 17.

Department of Hematology and Oncology, Mie University Hospital, Japan.

Pulmonary mucormycosis (PM) is a life-threatening fungal infection in patients with hematologic malignancies, and early and accurate diagnostic modalities are urgently needed. We conducted a polymerase chain reaction (PCR) assay targeting these fungi in peripheral blood from four patients with hematologic malignancies who were strongly suspected of having PM. In these four patients, the Rhizopus species was identified in two patients, and the Cunninghamella and Absidia species in one each. Based on these molecular findings, all of the patients were successfully treated via targeted therapy with liposomal amphotericin B. In this report, a PCR analysis proved very useful for managing PM in patients with hematologic malignancies.
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http://dx.doi.org/10.2169/internalmedicine.56.7647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410485PMC
May 2017

Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan.

J Clin Oncol 2017 Jan 31;35(1):32-39. Epub 2016 Oct 31.

Motoko Yamaguchi, Kana Miyazaki, Noriko Ii, and Naoyuki Katayama, Mie University Graduate School of Medicine, Tsu; Ritsuro Suzuki, Shimane University Hospital, Izumo; Masahiko Oguchi and Kyoko Ueda, Cancer Institute Hospital of the Japanese Foundation for Cancer Research; Yukio Kobayashi and Jun Itami, National Cancer Center Hospital; Bungo Saito, Showa University School of Medicine, Tokyo; Naoko Asano, Nagano Prefectural Suzaka Hospital, Suzaka; Jun Amaki and Takeshi Akiba, Tokai University School of Medicine, Isehara; Takeshi Maeda and Satoshi Itasaka, Kurashiki Central Hospital, Kurashiki; Nobuko Kubota and Yoshihiro Saito, Saitama Cancer Center, Ina; Naoto Tomita, Yokohama City University Graduate School of Medicine, Yokohama; Nodoka Sekiguchi, Shinshu University School of Medicine, Matsumoto; Jun Takizawa, Niigata University Faculty of Medicine, Niigata; Tohru Murayama, Hyogo Cancer Center, Akashi; Toshihiko Ando, Saga University, Saga; Hideho Wada, Kawasaki Medical School, Kurashiki; Rie Hyo, Nagoya University Graduate School of Medicine, Nagoya; Yasuo Ejima, Kobe University, Kobe; and Masatoshi Hasegawa, Nara Medical University, Kashihara, Japan.

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients' median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase-containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.
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http://dx.doi.org/10.1200/JCO.2016.68.1619DOI Listing
January 2017

Treatment of Diffuse Large B-Cell Lymphoma.

Authors:
Kana Miyazaki

J Clin Exp Hematop 2016 ;56(2):79-88

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

Diffuse large B-cell lymphoma (DLBCL) comprises a heterogeneous group with pathophysiological, genetic and clinical features. Many patients can be cured with R-CHOP therapy, which is the current standard regimen. Despite recent progress in improving patient survival, the 40% survival of DLBCL patients remains poor. Therefore, the most important issue for patients with DLBCL remains the development of a new front-line therapy. Several studies have reported that intensified chemotherapy with dose-adjusted EPOCH-R or R-ACVBP was superior to R-CHOP. Gene expression profiling has identified two distinct forms of DLBCL: activated B cell-like (ABC) and germinal center B-cell-like (GCB) types. ABC DLBCL exhibits a worse prognosis than GCB DLBCL by molecular diagnosis after R-CHOP therapy. Next-generation sequencing has identified unique oncogenic mechanisms and genetic complexity, which has provided rational therapeutic targets. There are also a number of biomarkers, including CD5, and prognostic factors. Efforts to distinguish many biomarkers will be crucial for individualized treatment in the future.
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http://dx.doi.org/10.3960/jslrt.56.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144206PMC
March 2017

MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma.

Cancer 2017 04 4;123(7):1166-1173. Epub 2016 Dec 4.

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

Background: CD5-positive (CD5 ) diffuse large B-cell lymphoma (DLBCL) is characterized by frequent central nervous system recurrence and a predominant activated B-cell-like nature. Primary DLBCL in sanctuary sites (DLBCL-SS) also demonstrates these features, and >70% of patients harbor myeloid differentiation primary response 88 (MYD88) (L265P) and CD79B mutations. The objective of the current study was to elucidate a possible relationship between CD5 DLBCL and DLBCL-SS.

Methods: MYD88, CD79B, CD79A, and caspase recruitment domain family member 11 (CARD11) mutations were examined in samples from 40 patients with CD5 DLBCL. Mutation analysis was performed by direct sequencing.

Results: MYD88 and CD79B mutations were detected in 33% (13 patients) and 38% (15 patients), respectively, of the 40 patients with CD5 DLBCL. Ten patients had these 2 gene mutations, and 1 had a CD79A mutation. One of 2 patients with testicular involvement had both MYD88 and CD79B mutations. The other patient had a MYD88 mutation alone. None of the 31 patients examined was found to have a CARD11 mutation. MYD88 and CD79B mutations were found to be associated with localized disease (P = .038 and P = .003, respectively). Primary extranodal lymphoma was associated with higher frequencies of mutations in MYD88 or both MYD88 and CD79B (P = .008 and P = .014, respectively). There was no significant difference in overall survival based on MYD88 and CD79B mutation status.

Conclusions: The incidence of MYD88 and CD79B mutations in patients with CD5 DLBCL is lower than that in patients with DLBCL-SS, suggesting that CD5 DLBCL is not the same disease as DLBCL-SS in terms of gene mutation status. CARD11 mutations are rare in patients with CD5 DLBCL. Cancer 2017;123:1166-1173. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30404DOI Listing
April 2017

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features.

Cancer Med 2016 08 17;5(8):1802-9. Epub 2016 May 17.

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

Diffuse large B-cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5-positive (CD5(+) ) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5(+) DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5, LMO3, SNAP25, SYT5, SV2C, CABP1, FGF1, FGFR2, NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B-cell-like DLBCL (P = 0.046). Compared to the SH3BP5-negative group, the SH3BP5(+) group was correlated with elderly onset (>60 years, P = 0.0096) and advanced-stage disease (stage III/IV, P = 0.037). The LMO3(+) group showed a worse performance status (>1, P = 0.0004). The SH3BP5(+) group and the LMO3(+) group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab-containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL.
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http://dx.doi.org/10.1002/cam4.753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873606PMC
August 2016

[Diffuse large B-cell lymphoma: therapeutic development based on clinical and biological heterogeneity].

Authors:
Kana Miyazaki

Rinsho Ketsueki 2015 Oct;56(10):2047-55

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, and is regarded as a heterogeneous group of lymphomas in terms of morphologic, immunologic, and cytogenetic features. The current standard therapy for DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy, which allows many patients to achieve disease cure. Despite recent progress in improving patient survival, 40% of DLBCL outcomes are still unsatisfactory. Gene expression profiling has been used to identify two distinct forms of DLBCL: the activated B-cell (ABC) subtype and the germinal center B-cell (GCB) subtype, which reflects normal B-cell differentiation. ABC DLBCL has been reported to show a more activated phenotype and a poorer prognosis than the GCB subtypes, with molecular diagnosis after R-CHOP therapy. Next generation sequencing identified unique oncogenic mechanisms and genetic complexity, which provided rational therapeutic targets. Recent studies suggest that patients with double-hit lymphoma, i.e., dual rearrangements of MYC and BCL2, have an extremely grim prognosis. Moreover, there are a number of biomarkers including CD5 and prognostic factors. Efforts to distinguish among these biomarkers will be crucial for devising individualized treatments in the future.
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http://dx.doi.org/10.11406/rinketsu.56.2047DOI Listing
October 2015

[Relapse in the nasal cavity of a patient with extranodal NK/T-cell lymphoma initially presenting as plantar subcutaneous tumor].

Rinsho Ketsueki 2015 Aug;56(8):1076-81

Department of Haematology and Oncology, Mie University Graduate School of Medicine.

A 36-year-old woman complained of a mass on the sole of her foot in February 200X. She was diagnosed with extranodal NK/T-cell lymphoma, nasal type (ENKL) by skin biopsy. Because the lesion was localized on the subcutaneous tissue of the sole, she was treated with RT/2/3DeVIC, resulting in a complete response (CR). In March of the following year, PET/CT showed significant uptake and mucosal thickening in the right nasal cavity, and a mucosal biopsy confirmed ENKL infiltration. Because the lesion was localized in the nasal cavity, she was re-treated with RT/2/3DeVIC, with a focus on local control, and she achieved a second CR. She subsequently received allogeneic hematopoietic stem cell transplantation in the hope of preventing systemic relapse. She has remained in CR for four years since the transplantation. Our case suggests that allogeneic hematopoietic stem cell transplantation to be a potentially promising approach to curative treatment for recurrent ENKL in younger patients. As nasal lesions may subsequently appear during the course of primary non-nasal ENKL, ongoing meticulous evaluation for nasal lesions is important.
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http://dx.doi.org/10.11406/rinketsu.56.1076DOI Listing
August 2015

[CD5-positive DLBCL: molecular basis and treatment strategies].

Authors:
Kana Miyazaki

Rinsho Ketsueki 2015 Aug;56(8):1038-44

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) comprises 10% of DLBCL and is one of the immunohistochemical subgroups in the 2008 WHO classification. It shows many distinct clinical characteristics including elderly onset, advanced stage at diagnosis, high serum lactate dehydrogenase level and frequent involvement of extranodal sites. CD5+ DLBCL has a poor prognosis and a relatively high incidence of central nervous system (CNS) relapse even in the rituximab era. Eighty-three percent of patients who experienced CNS relapse had brain parenchymal disease. Immunohistochemically, 82% of CD5+ DLBCLs are classified as the non-germinal center B-cell type. BCL2 protein is positive in more than 70% of patients. P-glycoprotein, which is associated with multidrug resistance, was positive in 59% of patients with CD5+ DLBCL tested at Mie University Hospital. Based on gene expression profiling, most patients with CD5+ DLBCL are classified as activated B-cell-like (ABC) DLBCL. A more effective first-line therapy for CD5+ DLBCL needs to be explored. In Mie University Hospital, four patients with newly diagnosed stage IV CD5+ DLBCL were successfully treated with dose-adjusted (DA)-EPOCH-R combined with hi-dose methotrexate (HD-MTX). Based on these observations, a phase II study of DA-EPOCH-R/HD-MTX for newly diagnosed CD5+ DLBCL (PEARL5 trial) is ongoing in Japan.
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http://dx.doi.org/10.11406/rinketsu.56.1038DOI Listing
August 2015

Gene expression profiling of diffuse large B-Cell lymphomas supervised by CD5 expression.

Int J Hematol 2015 Aug 26;102(2):188-94. Epub 2015 May 26.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan,

CD5-positive (CD5(+)) diffuse large B-cell lymphoma (DLBCL) has a poor prognosis and high incidence of central nervous system (CNS) relapse, even in the rituximab era. To determine the gene expression profile of CD5(+) DLBCL, total RNA from 90 patients with DLBCL, including 33 CD5(+) DLBCL and 57 CD5-negative (CD5(-)) DLBCL patients, was examined using Agilent human oligo microarrays. These cases were separated into 78 activated B-cell-like (ABC) DLBCLs and 12 germinal center B-cell-like (GCB) DLBCLs. All cases of CD5(+) DLBCL were classified as ABC DLBCLs. The classifier based on gene expression used in a supervised analysis correctly identified CD5 expression in the DLBCL and ABC DLBCL samples. The gene most relevant to CD5 expression was SH3BP5. Enriched GO categories in the CD5(+) ABC DLBCL signature gene set included multicellular organismal signaling, transmission of nerve impulse, and synaptic transmission. The present study, which includes the largest reported number of patients with CD5(+) DLBCL, confirmed that most CD5(+) DLBCLs are ABC DLBCLs, suggesting that therapeutic strategies for ABC DLBCL may be effective for the treatment of CD5(+) DLBCL. Our CD5(+) ABC DLBCL signature gene set may provide insights into the cause of the high frequency of CNS relapse in CD5(+) DLBCL.
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http://dx.doi.org/10.1007/s12185-015-1812-2DOI Listing
August 2015

Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Cancer Sci 2014 Nov 4;105(11):1435-41. Epub 2014 Oct 4.

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

Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61-94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057-1.013; 80% CI, 0.093-0.615; P = 0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of αβ T-cell origin and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.
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http://dx.doi.org/10.1111/cas.12526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462380PMC
November 2014

[Treatment approaches for diffuse large B-cell lymphoma].

Nihon Rinsho 2014 Mar;72(3):483-7

Diffuse large B-cell lymphoma(DLBCL) is the most common non-Hodgkin lymphoma, and is regarded as a heterogeneous group of lymphomas in terms of morphologic, immunologic, and cytogenetic features. The 2008 WHO classification divides DLBCL into subtypes based on clinical, morphological, immunological, and genetic features. The current standard of care for DLBCL is CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) combined with rituximab, anti-CD20 antibody, allowing many patients to achieve disease cure. Despite of recent progress in improving patient survival, clinical outcomes are still unsatisfactory for certain subtypes of DLBCL. This review outlines the current treatment strategy for DLBCL and focuses on recent clinical trials in Japan for particular subgroups of DLBCL.
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March 2014

Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis.

Kidney Int 2010 Nov 18;78(10):1016-23. Epub 2010 Aug 18.

Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan.

IgG4-related disease is a recently recognized multi-organ disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive cells into several organs. Although the pancreas was the first organ recognized to be affected by IgG4-related disorder in the syndrome of autoimmune pancreatitis, we present here clinico-pathological features of 23 patients diagnosed as having renal parenchymal lesions. These injuries were associated with a high level of serum IgG4 and abundant IgG4-positive plasma cell infiltration into the renal interstitium with fibrosis. In all patients, tubulointerstitial nephritis was the major finding. Although 14 of the 23 patients did not have any pancreatic lesions, their clinicopathological features were quite uniform and similar to those shown in autoimmune pancreatitis. These included predominance in middle-aged to elderly men, frequent association with IgG4-related conditions in other organs, high levels of serum IgG and IgG4, a high frequency of hypocomplementemia, a high serum IgE level, a patchy and diffuse lesion distribution, a swirling fibrosis in the renal pathology, and a good response to corticosteroids. Thus, we suggest that renal parenchymal lesions actually develop in association with IgG4-related disease, for which we propose the term 'IgG4-related tubulointerstitial nephritis.'
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http://dx.doi.org/10.1038/ki.2010.271DOI Listing
November 2010

[Long-term remission of a nasal NK/T-cell lymphoma patient with massive involvement of the orbita and liver dysfunction].

Rinsho Ketsueki 2009 Jan;50(1):44-8

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

A 49-year-old woman with high fever and diffuse swelling of the right cheek was referred to our hospital. Computed tomography showed right orbital tumor with massive involvement. Histopathologic examination of the biopsied right orbital tumor demonstrated extranodal NK/T-cell lymphoma, nasal-type. She was treated with six courses of chemotherapy consisting of etoposide and dexamethasone with 50 Gy of concurrent involved-field radiotherapy. Facial swelling and liver dysfunction improved immediately, and after five courses of chemotherapy, she achieved partial remission without any severe adverse events. L-asparaginase was administered in the final course of chemotherapy. There is no evidence of recurrence 56 months after diagnosis.
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January 2009

Gene expression profiling of peripheral T-cell lymphoma including gammadelta T-cell lymphoma.

Blood 2009 Jan 27;113(5):1071-4. Epub 2008 Oct 27.

Department of Hematology, Mie University Graduate School of Medicine, Tsu, Japan.

The gene expression profile of peripheral gammadelta T-cell lymphoma (gammadeltaTCL) has not been investigated. Using oligonucleotide microarrays, we analyzed total RNA from 7 patients with gammadeltaTCL (4 hepatosplenic, 1 cutaneous, 1 intestinal, and 1 thyroidal) and 27 patients with alphabetaTCL (11 peripheral TCL-unspecified, 15 angioimmunoblastic TCL, and 1 hepatosplenic). Unsupervised microarray analyses classified all hepatosplenic gammadeltaTCLs into a single cluster, whereas other gammadeltaTCLs were scattered within the alphabetaTCL distribution. We identified a T-cell receptor signature gene set, which accurately classified gammadeltaTCL and alphabetaTCL. A classifier based on gene expression under supervised analysis correctly identified gammadeltaTCL. One case of hepatosplenic alphabetaTCL was placed in the gammadeltaTCL grouping. gammadeltaTCL signature genes included genes encoding killer cell immunoglobulin-like receptors and killer cell lectin-like receptors. Our results indicate that hepatosplenic gammadeltaTCL is a distinct form of peripheral TCL and suggest that nonhepatosplenic gammadeltaTCLs are heterogeneous in gene expression.
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http://dx.doi.org/10.1182/blood-2008-07-166363DOI Listing
January 2009

Deletion of chromosome arm 15q in a case of minimally differentiated hypoplastic AML-M0.

Cancer Genet Cytogenet 2008 Jul;184(1):57-61

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 Japan.

Deletion of the long arm of chromosome 15 is known as a rare but recurrent chromosomal abnormality in myeloid malignancies. We report a novel case of minimally differentiated hypoplastic acute myeloid leukemia (AML M0) in a patient who initially had a normal karyotype, but clonal interstitial deletion of chromosome 15, del(15)(q11.2q22), coincided with increment of leukemic cells a year later. We also summarize 18 published cases with myeloid malignancies and this chromosomal abnormality.
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http://dx.doi.org/10.1016/j.cancergencyto.2008.03.010DOI Listing
July 2008
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