Annual Report 2019
Department of Hematology
Yosuke Minami, Junichiro Yuda, Nobuhiko Yamauchi, Kenichi Miyamoto, Yusuke Kamihara
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 patients with newly diagnosed hematologic malignancies in our department are increasing, and approximately 300 patients with newly diagnosed hematologic malignancies including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, acute/chronic leukemia, and 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
The purpose is to promote understanding about patients with hematologic malignancies including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, acute/chronic leukemia, and myelodysplastic syndrome for residents. 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 patients with hematologic malignancies including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, acute/chronic leukemia, and myelodysplastic syndrome.
List of papers published in 2019
Journal
1. 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
2. Shinohara H, Sugito N, Kuranaga Y, Heishima K, Minami Y, Naoe T, Akao Y. Potent antiproliferative effect of fatty-acid derivative AIC-47 on leukemic mice harboring BCR-ABL mutation. Cancer Sci, 110:751-760, 2019
3. Terao T, Minami Y. Targeting Hedgehog (Hh) Pathway for the Acute Myeloid Leukemia Treatment. Cells, 8:E312, 2019
4. Miyamoto K, Minami Y. Precision medicine and novel molecular target therapies in acute myeloid leukemia: the background of hematologic malignancies (HM)-SCREEN-Japan 01. Int J Clin Oncol, 24:893-898, 2019
5. Shinohara H, Minami Y, Naoe T, Akao Y. Autophagic degradation determines the fate of T315I-mutated BCR-ABL protein. Haematologica, 104:e191-e194, 2019