Annual Report 2020
Department of Hematology
Yosuke Minami, Junichiro Yuda, Nobuhiko Yamauchi, Yongmei Guo, Hirotaka Nakamura, SungGi Chi, Akihito Nagata
Introduction
The staff-physicians and residents of the Department of Hematology carry out clinical and research activities related to multi-disciplinary treatment of patients with hematological malignancies which consists of more than 100 disease entities in the WHO classification. Our department focuses on early and late phases of clinical trials in collaboration with the Research Center for Innovative Oncology on hematological malignancies.
The Team and What We Do
The number of patients with newly diagnosed hematologic malignancies in our department is increasing, and approximately 300 patients newly diagnosed with hematologic malignancies including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, acute/chronic leukemia, myelodysplastic syndrome were cared for this year. Our department is currently providing routine chemotherapy as an outpatient service for an increasing number of relatively aged patients with hematologic malignancies. All patients undergoing intensive chemotherapy and autologous peripheral blood hematopoietic stem cell transplantation (APBSCT) are managed in laminar airflow rooms at the designated ward on the eighth floor. Besides managing patients, our department also provides consultations on hematological abnormalities detected in the Department of Clinical Laboratories. Morning case conferences on the inpatient care of our department are held from Mondays to Fridays, and weekly case conferences for new patients visiting our clinic are held on Thursday evenings. On Wednesday evenings, joint conferences on lymphoid malignancies with expert pathologists and educational cytology conferences on bone marrow specimens are held.
Research activities
Ancillary studies associated with retrospective case series and clinical trials at this department have been continuously conducted focusing on several kinds of hematologic malignancies and their complications. Recently, a nationwide survey of human T-lymphotropic virus type I (HTLV-1) associated adult T-cell leukemia-lymphoma (ATL) is ongoing by us under a grant for Cancer Research from the Ministry of Health, Labour and Welfare to elucidate the pathophysiology including geographical findings as compared to the previous surveys. We also carry out translational research regarding hematologic malignancies.
Clinical trials
Clinical trials on hematological malignancies performed by our department comprise protocols prepared in-house and participation in the Japan Clinical Oncology Group-Lymphoma Study Group (JCOG-LSG), the Japan Adult Leukemia Study Group (JALSG) and others.
The department participated in pharmaceutical company-sponsored and investigator-initiated new-agent trials including international ones for hematological malignancies. The following JCOG clinical trials are ongoing: a randomized phase III trial of rituximab administered weekly or triweekly with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in patients with newly diagnosed CD20+ diffuse large B cell lymphoma (DLBCL) (JCOG0601) in which a dose-intense schedule of rituximab is evaluated; a randomized phase II trial comparing biweekly rituximab-CHOP or biweekly rituximab-CHOP/cyclophosphamide, cytarabine, dexamethasone, etoposide and rituximab (CHASER) followed by high dose melphalan, cyclophosphamide, etoposide and dexamethasone (LEED) with APBSCT in patients with newly diagnosed poor risk CD20+ DLBCL (JCOG0908); a randomized phase II study of two induction treatments of melphalan, prednisolone, plus bortezomib (MPB), JCOG-MPB versus modified PETHEMA-MPB, in elderly patients or non-elderly patients refusing transplants with untreated symptomatic myeloma (JCOG1105); and a single armed phase III study of mLSG15 chemotherapy followed by allo-HSCT, comparing the results with historical control in JCOG9801 of mLSG15 alone to evaluate the promising efficacy of allo-HSCT, possibly associated
with a graft-versus-ATL effect, especially in view of a comparison with intensive chemotherapy (JCOG0907). A phase III study evaluating the efficacy of the combination of interferon-alpha (IFN) and zidovudine (AZT) as compared to watchful-waiting for indolent ATL (JCOG1111) is ongoing under a highly advanced medical technology assessment system because IFN and AZT are not covered for ATL by National Health Insurance in Japan. A single armed phase III study of interim-PET response adapted a switch-strategy from ABVD to ABVD/DE-BEACOP for advanced Hodgkin Lymphoma (JCOG1305).
Education
We train our residents to promote understanding about patients with hematologic malignancies including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, acute/chronic leukemia, myelodysplastic syndrome. To disseminate knowledge about hematologic malignancies, we held several workshops for medical staff in the National Cancer Center Hospital East (NCCHE).
Future Prospects
Our Department will continue the above activities and develop new research to improve the treatment for patients with hematologic malignancies including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, acute/chronic leukemia, myelodysplastic syndrome.
List of papers published in 2020
Journal
1. Yamauchi N, Maruyama D, Choi I, Atsuta Y, Sakai R, Miyashita K, Moriuchi Y, Tsujimura H, Kubota N, Yamamoto G, Igarashi T, Izutsu K, Yoshida S, Kojima K, Uchida T, Inoue Y, Tsukamoto N, Ohtsuka E, Suzuki S, Inaguma Y, Ichikawa S, Gomyo H, Ushijima Y, Nosaka K, Kurata M, Tanaka Y, Ueda R, Mizokami M, Kusumoto S. Prophylactic antiviral therapy for hepatitis B virus surface antigen-positive patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy. Cancer Sci, 112:1943-1954, 2021
2. Nozaki K, Maruyama D, Maeshima AM, Tajima K, Itami J, Shichijo T, Yuda S, Suzuki T, Toyoda K, Yamauchi N, Makita S, Fukuhara S, Munakata W, Kobayashi Y, Taniguchi H, Izutsu K, Tobinai K. The role of local radiotherapy following rituximab-containing chemotherapy in patients with transformed indolent B-cell lymphoma. Eur J Haematol, 106:213-220, 2021
3. Tabata R, Chi S, Yuda J, Minami Y. Emerging Immunotherapy for Acute Myeloid Leukemia. Int J Mol Sci, 22:2021
4. Ohmachi K, Kinoshita T, Tobinai K, Ogawa G, Mizutani T, Yamauchi N, Fukuhara N, Uchida T, Yamamoto K, Miyazaki K, Tsukamoto N, Iida S, Utsumi T, Yoshida I, Imaizumi Y, Tokunaga T, Yoshida S, Masaki Y, Murayama T, Yakushijin Y, Suehiro Y, Nosaka K, Dobashi N, Kuroda J, Takamatsu Y, Maruyama D, Ando K, Ishizawa K, Ogura M, Yoshino T, Hotta T, Tsukasaki K, Nagai H. A randomized phase 2/3 study of R-CHOP vs CHOP combined with dose-dense rituximab for DLBCL: the JCOG0601 trial. Blood Adv, 5:984-993, 2021
5. Tabata R, Sato N, Yamauchi N, Guo YM, Nakamura H, Nagata A, Song-Gi C, Minami Y, Yuda J. Cytomegalovirus reactivation in patients with multiple myeloma administered daratumumab-combination regimens. Ann Hematol, 2021
6. Yuda J, Yamauchi N, Kuzume A, Guo YM, Sato N, Minami Y. Molecular remission after combination therapy with blinatumomab and ponatinib with relapsed/refractory Philadelphia chromosome-positive acute lymphocytic leukemia: two case reports. J Med Case Rep, 15:164, 2021
7. Terao T, Yuda J, Yamauchi N, Guo YM, Shimada K, Sugano M, Ishii G, Minami Y. Brentuximab vedotin maintenance after autologous stem cell transplantation for refractory gray zone lymphoma with long-term remission. Mol Clin Oncol, 14:125, 2021
8. Murata M, Suzuki R, Nishida T, Shirane S, Shimazu Y, Minami Y, Mori T, Doki N, Kanda Y, Uchida N, Tanaka M, Ishikawa J, Togitani K, Fukuda T, Ichinohe T, Atsuta Y, Nagamura-Inoue T, Kiyoi H. Allogeneic Hematopoietic Stem Cell Transplantation for Post-essential Thrombocythemia and Post-polycythemia Vera Myelofibrosis. Intern Med, 59:1947-1956, 2020
9. Izutsu K, Minami Y, Fukuhara N, Terui Y, Jo T, Yamamoto G, Ishikawa T, Kobayashi T, Kiguchi T, Nagai H, Ohtsu T, Kalambakas S, Fustier P, Midorikawa S, Tobinai K. Analysis of Japanese patients from the AUGMENT phase III study of lenalidomide + rituximab (R(2)) vs. rituximab + placebo in relapsed/refractory indolent non-Hodgkin lymphoma. Int J Hematol, 111:409-416, 2020
10. Yuda J, Odawara J, Minami M, Muta T, Kohno K, Tanimoto K, Eto T, Shima T, Kikushige Y, Kato K, Takenaka K, Iwasaki H, Minami Y, Ohkawa Y, Akashi K, Miyamoto T. Tyrosine kinase inhibitors induce alternative spliced BCR-ABL(Ins35bp) variant via inhibition of RNA polymerase II on genomic BCR-ABL. Cancer Sci, 111:2361-2373, 2020
11. Miyamoto K, Minami Y. Cutting Edge Molecular Therapy for Acute Myeloid Leukemia. Int J Mol Sci, 21:2020
12. Eguchi M, Minami Y, Kuzume A, Chi S. Mechanisms Underlying Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia. Biomedicines, 8:2020
13. Kuzume A, Chi S, Yamauchi N, Minami Y. Immune-Checkpoint Blockade Therapy in Lymphoma. Int J Mol Sci, 21:2020
14. Nagasaki J, Togashi Y, Sugawara T, Itami M, Yamauchi N, Yuda J, Sugano M, Ohara Y, Minami Y, Nakamae H, Hino M, Takeuchi M, Nishikawa H. The critical role of CD4+ T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma. Blood Adv, 4:4069-4082, 2020
15. Shichijo T, Maruyama D, Yamauchi N, Maeshima AM, Sugano M, Yuda S, Tajima K, Kurihara H, Shimada K, Suzuki T, Toyoda K, Makita S, Fukuhara S, Munakata W, Suzuki T, Kobayashi Y, Taniguchi H, Minami Y, Izutsu K, Tobinai K. Transformation Scoring System (TSS): A new assessment index for clinical transformation of follicular lymphoma. Cancer Med, 9:8864-8874, 2020
16. Izumi S, Minami Y, Masuda S, Utsu Y, Sakaida E, Aotsuka N. Emergence of natural killer cell large granular lymphocytes during gilteritinib treatment in acute myeloid leukemia with FLT3-ITD mutation. Reports, 3:E25, 2020