Annual Report 2023
Department of Hematology
Yosuke Minami, Junichiro Yuda, Nobuhiko Yamauchi, Yongmei Guo, Hirotaka Nakamura, SungGi Chi, Ryo Yoshimaru
Introduction
The staff-physicians and residents of the Department of Hematology conduct clinical and research activities related to multi-disciplinary treatment of patients with hematological malignancies, including more than 100 disease entities classified by the WHO. Our department focuses on the 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 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 outpatient chemotherapy 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. In addition to managing patients, our department provides consultations on hematological abnormalities detected by the Department of Clinical Laboratories. Morning case conferences on the inpatient care of our department are held from Mondays to Fridays, while weekly case conferences for new patients visiting our clinic are held every Thursday evening. Joint conferences on lymphoid malignancies with expert pathologists and educational cytology conferences on bone marrow specimens are held every Wednesday evening.
Research Activities
Ancillary studies associated with retrospective case series and clinical trials have been continuously conducted at this department, focusing on several kinds of hematologic malignancies and their complications. Recently, our nationwide survey of human T-lymphotropic virus type I (HTLV-1) associated adult T-cell leukemia-lymphoma (ATL) is ongoing 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 conduct translational research regarding hematologic malignancies.
Clinical Trials
Our department performed clinical trials on hematological malignancies, including protocols prepared in-house and in participation with 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:
1. 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.
2. 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).
3. 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).
4. 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).
5. 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.
6. 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 at the National Cancer Center Hospital East (NCCHE).
Future Prospects
Our department will continue the above activities and develop new research to improve management of 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 2023
Journal
1. Arai H, Matsui H, Chi S, Utsu Y, Masuda S, Aotsuka N, Minami Y. Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome. International journal of molecular sciences, 25:652, 2024
2. Hashimoto T, Nakamura Y, Oki E, Kobayashi S, Yuda J, Shibuki T, Bando H, Yoshino T. Bridging horizons beyond CIRCULATE-Japan: a new paradigm in molecular residual disease detection via whole genome sequencing-based circulating tumor DNA assay. International journal of clinical oncology, 29:495-511, 2024
3. Uchiyama S, Fukushima K, Katagiri S, Tsuchiya J, Kubo T, Chi S, Minami Y. Advancements in minimal residual disease detection: a practical approach using single-cell droplet PCR for comprehensive monitoring in hematological malignancy. Therapeutic advances in hematology, 15:20406207241245510, 2024
4. Jabbour E, Kantarjian HM, Aldoss I, Montesinos P, Leonard JT, Gómez-Almaguer D, Baer MR, Gambacorti-Passerini C, McCloskey J, Minami Y, Papayannidis C, Rocha V, Rousselot P, Vachhani P, Wang ES, Wang B, Hennessy M, Vorog A, Patel N, Yeh T, Ribera JM. Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA, 331:1814-1823, 2024
5. Izutsu K, Kumode T, Yuda J, Nagai H, Mishima Y, Suehiro Y, Yamamoto K, Fujisaki T, Ishitsuka K, Ishizawa K, Ikezoe T, Nishikori M, Akahane D, Fujita J, Dinh M, Soong D, Noguchi H, Buchbjerg JK, Favaro E, Fukuhara N. Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. Cancer science, 114:4643-4653, 2023
6. Réa D, Boquimpani C, Mauro MJ, Minami Y, Allepuz A, Maheshwari VK, D'Alessio D, Wu Y, Lawrance R, Narbutas S, Sharf G, Hochhaus A. Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial. Leukemia, 37:1060-1067, 2023
7. Katagiri S, Furuya N, Akahane D, Chi S, Minami Y, Harada Y, Harada H, Gotoh A. Gilteritinib Affects the Selection of Dominant Clones in Clonal Hematopoiesis: Sequential Genetic Analysis of an FLT3-ITD Positive AML Patient with Long-Term Gilteritinib Therapy. OncoTargets and therapy, 16:571-576, 2023
8. Yoshimaru R, Minami Y. Genetic Landscape of Chronic Myeloid Leukemia and a Novel Targeted Drug for Overcoming Resistance. International journal of molecular sciences, 24:2023
9. Yuda J, Will C, Phillips DC, Abraham L, Alvey C, Avigdor A, Buck W, Besenhofer L, Boghaert E, Cheng D, Cojocari D, Doyle K, Hansen TM, Huang K, Johnson EF, Judd AS, Judge RA, Kalvass JC, Kunzer A, Lam LT, Li R, Martin RL, Mastracchio A, Mitten M, Petrich A, Wang J, Ward JE, Zhang H, Wang X, Wolff JE, Bell-McGuinn KM, Souers AJ. Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients. Communications medicine, 3:154, 2023
10. Ogata H, Minami Y. An HSP90 Inhibitor Overcomes FLT3 Inhibitor Resistance in FLT3/ITD-Positive Leukemia Cells with an N676K Mutation. International Journal of Translational Medicine, 3:389-398, 2023