Department of Hematology

Yosuke Minami, Junichiro Yuda, Nobuhiko Yamauchi, Yongmei Guo, Hirotaka Nakamura, Sunggi Chi, Akihito Nagata, Satoshi Uchiyama

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 consist of more than 100 disease entities in the WHO classification. Our department focuses on early and late phases of clinical trials on hematological malignancies in collaboration with the Research Center for Innovative Oncology.

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 Monday to Friday, 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)

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 outcomes for patients with hematologic malignancies including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, acute/chronic leukemia, and myelodysplastic syndrome.

List of papers published

Journal

1. Chi SG, Minami Y. Emerging Targeted Therapy for Specific Genomic Abnormalities in Acute Myeloid Leukemia. International journal of molecular sciences, 23:2022

2. Suga M, Fukushima K, Ueda T, Arai Y, Nakagawa S, Minami Y, Toda J, Hino A, Fujita J, Yokota T, Hosen N. Clinical implications of combination therapy with quizartinib and craniospinal irradiation for refractory acute myeloid leukemia positive for FMS-like tyrosine kinase 3-internal tandem duplication with central nervous system involvement. Clinical case reports, 10:e05384, 2022

3. Tsushima T, Sato N, Guo YM, Uchiyama S, Nakamura H, Nagata A, Song-Gi C, Yamauchi N, Minami Y, Yuda J. Combination therapy with low doses of ponatinib and steroids in elderly and frail patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Annals of hematology, 2022

4. Jinnouchi F, Mori Y, Yoshimoto G, Yamauchi T, Nunomura T, Yurino A, Hayashi M, Yuda J, Shima T, Odawara J, Takashima S, Kamezaki K, Kato K, Miyamoto T, Akashi K, Takenaka K. Incidence of refractory cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. International journal of hematology, 115:96-106, 2022

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. Annals of hematology, 101:465-467, 2022

6. Tabata R, Chi S, Yuda J, Minami Y. Emerging Immunotherapy for Acute Myeloid Leukemia. International journal of molecular sciences, 22:2021

7. 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. Journal of medical case reports, 15:164, 2021

8. H Nakamura, Y Minami, SG Chi, A Nagata, S Uchiyama, N Yamauchi. Emerging Mitochondria-Associated Molecular Target Therapies for Acute Myeloid Leukemia. Arch Clin Biomed Res, 5:419-424, 2021

9. Réa D, Mauro MJ, Boquimpani C, Minami Y, Lomaia E, Voloshin S, Turkina A, Kim DW, Apperley JF, Abdo A, Fogliatto LM, Kim DDH, le Coutre P, Saussele S, Annunziata M, Hughes TP, Chaudhri N, Sasaki K, Chee L, García-Gutiérrez V, Cortes JE, Aimone P, Allepuz A, Quenet S, Bédoucha V, Hochhaus A . A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood, 138:2031-2041, 2021

10. S Uchiyama, H Shinohara, SG Chi, YM Guo, J Yuda, T Ono, Y Minami. STAMP inhibitor Asciminib and medium-chain fatty-acid derivative AIC-47: novel therapies for chronic myeloid leukemia. Hematol Med Oncol, 6:2021

11. Fujioka Y, Sugiyama D, Matsumura I, Minami Y, Miura M, Atsuta Y, Ohtake S, Kiyoi H, Miyazaki Y, Nishikawa H, Takahashi N. Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia. Cancers, 13:2021

12. Murai K, Ureshino H, Kumagai T, Tanaka H, Nishiwaki K, Wakita S, Inokuchi K, Fukushima T, Yoshida C, Uoshima N, Kiguchi T, Mita M, Aoki J, Kimura S, Karimata K, Usuki K, Shimono J, Chinen Y, Kuroda J, Matsuda Y, Nakao K, Ono T, Fujimaki K, Shibayama H, Mizumoto C, Takeoka T, Io K, Kondo T, Miura M, Minami Y, Ikezoe T, Imagawa J, Takamori A, Kawaguchi A, Sakamoto J, Kimura S. Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial. The Lancet. Haematology, 8:e902-e911, 2021

13. Sasaki Y, Guo YM, Goto T, Ubukawa K, Asanuma K, Kobayashi I, Sawada K, Wakui H, Takahashi N. IL-6 Generated from Human Hematopoietic Stem and Progenitor Cells through TLR4 Signaling Promotes Emergency Granulopoiesis by Regulating Transcription Factor Expression. Journal of immunology (Baltimore, Md.: 1950), 207:1078-1086, 2021

14. 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. Molecular and clinical oncology, 14:125, 2021