Annual Report 2022

Department of Hematology

Yosuke Minami, Junichiro Yuda, Nobuhiko Yamauchi, Yongmei Guo, Hirotaka Nakamura, SungGi Chi, Satoshi Uchiyama

Introduction

 The staff-physicians and residents of the Department of Hematology conduct clinical and research activities related to multidisciplinary 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 a laminar airflow rooms at a 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 2022

Journal

1. Hosono N, Chi S, Yamauchi T, Fukushima K, Shibayama H, Katagiri S, Gotoh A, Eguchi M, Morishita T, Ogasawara R, Kondo T, Yanada M, Yamamoto K, Kobayashi T, Kuroda J, Usuki K, Utsu Y, Yoshimitsu M, Ishitsuka K, Ono T, Takahashi N, Iyama S, Kojima K, Nakamura Y, Fukuhara S, Izutsu K, Abutani H, Yamauchi N, Yuda J, Minami Y. Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01. Cancer science, 114:2098-2108, 2023

2. Nakagama Y, Chi SG, Minami Y, Watanabe R, Yamagishi M, Atsuko U, Kido Y. Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination. Journal of infection and chemotherapy, 29:112-114, 2023

3. Yuda J, Doki N, Matsuoka H, Yokota T, Tomita A, Takahashi N, Matsumura I, Kubo K, Goto T, Kirito K, Maki A, Aoki M, Allepuz A, Minami Y. Asciminib vs bosutinib in CML patients pretreated with ≧2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Cancer medicine, 12:2990-2998, 2023

4. Atallah E, Mauro MJ, Hochhaus A, Boquimpani C, Minami Y, Maheshwari VK, Saini L, Corbin R, Réa D. Matching-adjusted indirect comparison of asciminib versus other treatments in chronic-phase chronic myeloid leukemia after failure of two prior tyrosine kinase inhibitors. Journal of cancer research and clinical oncology, 2023

5. Hochhaus A, Réa D, Boquimpani C, Minami Y, Cortes JE, Hughes TP, Apperley JF, Lomaia E, Voloshin S, Turkina A, Kim DW, Abdo A, Fogliatto LM, le Coutre P, Sasaki K, Kim DDH, Saussele S, Annunziata M, Chaudhri N, Chee L, García-Gutiérrez V, Kapoor S, Allepuz A, Quenet S, Bédoucha V, Mauro MJ. Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Leukemia, 37:617-626, 2023

6. Tahir SK, Calvo E, Carneiro BA, Yuda J, Shreenivas A, Jongen-Lavrencic M, Gort E, Ishizawa K, Morillo D, Biesdorf C, Smith M, Cheng D, Motwani M, Sharon D, Uziel T, Modi DA, Buchanan FG, Morgan-Lappe S, Medeiros BC, Phillips DC. Activity of eftozanermin alfa plus venetoclax in preclinical models and patients with acute myeloid leukemia. Blood, 2023

7. Urabe A, Chi S, Minami Y. The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia. International journal of molecular sciences, 24:3727, 2023

8. Itahashi K, Irie T, Yuda J, Kumagai S, Tanegashima T, Lin YT, Watanabe S, Goto Y, Suzuki J, Aokage K, Tsuboi M, Minami Y, Ishii G, Ohe Y, Ise W, Kurosaki T, Suzuki Y, Koyama S, Nishikawa H. BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors. Science immunology, 7:eabk0957, 2022

9. Fukuhara S, Oshikawa-Kumade Y, Kogure Y, Shingaki S, Kariyazono H, Kikukawa Y, Koya J, Saito Y, Tabata M, Yoshifuji K, Mizuno K, Miyagi-Maeshima A, Matsushita H, Sugiyama M, Ogawa C, Inamoto Y, Fukuda T, Sugano M, Yamauchi N, Minami Y, Hirata M, Yoshida T, Kohno T, Kohsaka S, Mano H, Shiraishi Y, Ogawa S, Izutsu K, Kataoka K. Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies. Cancer science, 113:2763-2777, 2022

10. 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

11. Shimazu Y, Murata M, Kondo T, Minami Y, Tachibana T, Doki N, Uchida N, Ozawa Y, Yano S, Fukuda T, Kato J, Ara T, Eto T, Ishikawa J, Nakamae H, Tanaka J, Ichinohe T, Atsuta Y, Nagamura-Inoue T. The new generation tyrosine kinase inhibitor improves the survival of chronic myeloid leukemia patients after allogeneic stem cell transplantation. Hematological oncology, 40:442-456, 2022

12. Arai Y, Chi S, Minami Y, Yanada M. FLT3-targeted treatment for acute myeloid leukemia. International journal of hematology, 116:351-363, 2022

13. Katagiri S, Chi S, Minami Y, Fukushima K, Shibayama H, Hosono N, Yamauchi T, Morishita T, Kondo T, Yanada M, Yamamoto K, Kuroda J, Usuki K, Akahane D, Gotoh A. Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia. International journal of molecular sciences, 23:4694, 2022

14. Ikeda D, Chi S, Uchiyama S, Nakamura H, Guo YM, Yamauchi N, Yuda J, Minami Y. Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors. International journal of molecular sciences, 23:5950, 2022

15. Arai H, Minami Y, Chi S, Utsu Y, Masuda S, Aotsuka N. Molecular-Targeted Therapy for Tumor-Agnostic Mutations in Acute Myeloid Leukemia. Biomedicines, 10:3008, 2022