Department of Hematology

Koji Izutsu, Tatsuya Suzuki, Wataru Munakata, Suguru Fukuhara, Noriko Iwaki, Shinichi Makita, Yoshikazu Hori, Hirokazu Sasaki, Daiki Hattori

Introduction

The Department of Hematology of the National Cancer Center Hospital is dedicated to supporting patients with hematologic malignancies including leukemia, lymphoma, and myeloma by offering state-of-the-art diagnosis and treatment options and developing novel treatment and diagnostic methods through clinical trials and translational research. Our Lymphoma Program has a history of pioneering clinical research on adult T-cell leukemia/lymphoma and other lymphoid malignancies, and has been leading the development of novel agents and cell therapies for lymphoid malignancies in Japan.

The Team and What We Do

We offer the most advanced diagnostic procedures and care for patients with hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndrome, and multiple myeloma), both on an outpatient and inpatient basis (Table 1). The medical treatments we offer include chemotherapy, immunotherapy, and chimeric antigen receptor (CAR) T-cell therapy. We treat patients in collaboration with experts from our center's Department of Hematopoietic Stem Cell Transplantation, Department of Radiation Oncology, and Department of Experimental Therapeutics. Moreover, experts at our center's Department of Pathology and Department of Clinical Laboratories offer state-of-the-art diagnosis to guide treatment.

Table 1. The number of patients with newly diagnosed hematologic malignancies who were managed in the Department of Hematology.

Research activities

We have launched a tumor sample banking system for hematological malignancies for future research use. These samples include tumor DNA derived from bone marrow, peripheral blood, and other tumor tissue obtained through core needle biopsy. We are conducting clinical and clinical-pathology research for hematological malignancies, especially for malignant lymphoma. In 2018, in collaboration with other departments, we launched the MASTER KEY HEM registration study for rare hematologic malignancies incorporating biomarkers. In 2019, we launched an investigator-initiated clinical trial of a PD-L1 antibody for extranodal NK/T-cell lymphoma. Our department is devoted to activities of the leading clinical study groups on hematological malignancies in Japan, namely, the Japan Clinical Oncology Group ― Lymphoma Study Group (JCOG LSG) and the Japan Adult Leukemia Study Group (JALSG). This year, we authored or coauthored 29 articles related to hematological malignancies.

Clinical trials

In 2021, we conducted 69 corporate-sponsored clinical trials, including many global studies, one first-in-human study, and 8 new studies that started from April 2021 to March 2022. We also conducted several investigator-initiated clinical trials of JCOG and JALSG.

Education

We have been offering a training program for young hematologists and/or oncologists. Many of our graduates are actively engaged in hematology and oncology societies.

Future prospects

The Department of Hematology will continue to address unmet needs in the treatment of hematological malignancies. We are focusing on developing treatments for rare hematologic malignancies including rare subtypes of lymphoma. Our future plans include genome-based medicine. Information obtained from genomic tests has become imperative in the diagnosis according to the current WHO classification of hematologic malignancies, prognosis prediction, and for guiding selection of molecular-targeted agents.

List of papers published

Journal

1. Kato K, Makita S, Goto H, Kanda J, Fujii N, Shimada K, Akashi K, Izutsu K, Teshima T, Fukuda N, Sumitani T, Sumi H, Shimizu S, Kakurai Y, Yoshikawa K, Tobinai K, Usui N, Hatake K. Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma. International journal of clinical oncology, 27:213-223, 2022

2. Onishi A, Fuji S, Kitano S, Maeshima AM, Tajima K, Yamaguchi J, Kawashima I, Kawajiri A, Takemura T, Ito A, Tanaka T, Okinaka K, Inamoto Y, Kurosawa S, Kim SW, Munakata W, Maruyama D, Tobinai K, Fukuda T. Prognostic implication of CTLA-4, PD-1, and PD-L1 expression in aggressive adult T-cell leukemia-lymphoma. Annals of hematology, 101:799-810, 2022

3. Horwitz S, O’Connor OA, Pro B, Trümper L, Iyer S, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Menne T, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Zinzani PL, Miao H, Bunn V, Fenton K, Fanale M, Puhlmann M, Illidge T . The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Annals of oncology: official journal of the European Society for Medical Oncology, 33:288-298, 2022

4. Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G . Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. The New England journal of medicine, 386:351-363, 2022

5. Maeshima AM, Taniguchi H, Hattori D, Sasaki H, Hori Y, Makita S, Iwaki N, Fukuhara S, Munakata W, Suzuki T, Izutsu K. CD3-and CD20-negative extramedullary non-Hodgkin leukemia/lymphoma: a histopathological study of 118 cases. Human pathology, 124:14-23, 2022

6. Fukuhara N, Suehiro Y, Kato H, Kusumoto S, Coronado C, Rappold E, Zhao W, Li J, Gilmartin A, Izutsu K. Parsaclisib in Japanese patients with relapsed or refractory B-cell lymphoma (CITADEL-111): A phase Ib study. Cancer science, 113:1702-1711, 2022

7. Sekiguchi N, Rai S, Munakata W, Suzuki K, Handa H, Shibayama H, Endo T, Terui Y, Iwaki N, Fukuhara N, Tatetsu H, Iida S, Ishikawa T, Iguchi D, Izutsu K. Two-year outcomes of tirabrutinib monotherapy in WaldenstrÖm's macroglobulinemia. Cancer science, 113:2085-2096, 2022

8. Fujino T, Maruyama D, Maeshima AM, Saito Y, Ida H, Hosoba R, Yuda S, Makita S, Fukuhara S, Munakata W, Suzuki T, Kuroda J, Izutsu K. The outcome of watchful waiting in patients with previously treated follicular lymphoma. Cancer medicine, 11:2106-2116, 2022

9. Murayama K, Kiguchi T, Izutsu K, Kameoka Y, Hidaka M, Kato H, Rai S, Kuroda J, Ishizawa K, Ichikawa S, Ando K, Ogura M, Fukushima K, Terui Y. Bendamustine plus rituximab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma. Annals of hematology, 101:979-989, 2022

10. Nakamura N, Maruyama D, Machida R, Ichinohe T, Takayama N, Ohba R, Ohmachi K, Imaizumi Y, Tokunaga M, Katsuya H, Yoshida I, Sunami K, Kurosawa M, Kubota N, Morimoto H, Kobayashi M, Kato H, Kameoka Y, Kagami Y, Kizaki M, Takeuchi K, Munakata W, Iida S, Nagai H. Single response assessment of transplant-ineligible multiple myeloma: a supplementary analysis of JCOG1105 (JCOG1105S1). Japanese journal of clinical oncology, 51:1059-1066, 2021

11. Terui Y, Rai S, Izutsu K, Yamaguchi M, Takizawa J, Kuroda J, Ishikawa T, Kato K, Suehiro Y, Fukuhara N, Ohmine K, Goto H, Yamamoto K, Kanemura N, Ueda Y, Ishizawa K, Kumagai K, Kawasaki A, Saito T, Hashizume M, Shibayama H. A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B-cell lymphoma. Cancer science, 112:2845-2854, 2021

12. Kasane M, Kurosawa S, Kojima M, Iwashita N, Kase Y, Tsubokura M, Nakabayashi S, Ikeda C, Kawamura K, Matsushita H, Narita R, Fukumoto H, Fujino T, Makita S, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Ito A, Tanaka T, Inamoto Y, Kim SW, Tajima K, Tanosaki R, Izutsu K, Fukuda T. Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study. Transfusion and apheresis science: official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis, 60:103150, 2021

13. Kawai H, Ando K, Maruyama D, Yamamoto K, Kiyohara E, Terui Y, Fukuhara N, Miyagaki T, Tokura Y, Sakata-Yanagimoto M, Igarashi T, Kuroda J, Fujita J, Uchida T, Ishikawa T, Yonekura K, Kato K, Nakanishi T, Nakai K, Matsunaga R, Tobinai K. Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. Cancer science, 112:2426-2435, 2021

14. Izutsu K, Ando K, Nishikori M, Shibayama H, Teshima T, Kuroda J, Kato K, Imaizumi Y, Nosaka K, Sakai R, Hojo S, Nakanishi T, Rai S. Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan. Cancer science, 112:3627-3635, 2021

15. Takizawa J, Izutsu K, Nagai H, Fukase K, Nakamura M, Jinushi M, Suzumiya J. Real World Treatment Practices for Chronic Lymphocytic Leukemia in Japan: An Observational Database Research Study (CLIMBER-DBR). Journal of clinical and experimental hematopathology: JCEH, 61:126-134, 2021

16. Ida H, Inamoto Y, Fukuhara S, Maeshima AM, Takeda W, Hirakawa T, Kuno M, Aoki J, Tanaka T, Ito A, Kim SW, Izutsu K, Fukuda T. Outcomes of hematopoietic cell transplantation for transformed follicular lymphoma. Hematological oncology, 39:650-657, 2021

17. Izutsu K, Suzumiya J, Takizawa J, Fukase K, Nakamura M, Jinushi M, Nagai H. Real World Treatment Practices for Mantle Cell Lymphoma in Japan: An Observational Database Research Study (CLIMBER-DBR). Journal of clinical and experimental hematopathology: Journal of Clinical and Experimental Hematopathology, 61:135-144, 2021

18. Yuda S, Miyagi Maeshima A, Taniguchi H, Ito Y, Hatta S, Suzuki T, Makita S, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Izutsu K. Clinicopathological factors and tumor microenvironment markers predicting watch-and-wait discontinuation in 82 patients with follicular lymphoma. European journal of haematology, 107:157-165, 2021

19. Ito Y, Maeshima AM, Hatta S, Saito Y, Fujino T, Makita S, Fukuhara S, Munakata W, Taniguchi H, Suzuki T, Maruyama D, Sone M, Izutsu K. Use of Core-Needle Biopsy for the Diagnosis of Malignant Lymphomas in Clinical Practice. Acta haematologica, 144:641-648, 2021

20. Kaji D, Kusakabe M, Sakata-Yanagimoto M, Makishima K, Suehara Y, Hattori K, Ota Y, Mitsuki T, Yuasa M, Kageyama K, Taya Y, Nishida A, Ishiwata K, Takagi S, Yamamoto H, Asano-Mori Y, Ubara Y, Izutsu K, Uchida N, Wake A, Taniguchi S, Yamamoto G, Chiba S. Retrospective analyses of other iatrogenic immunodeficiency-associated lymphoproliferative disorders in patients with rheumatic diseases. British journal of haematology, 195:585-594, 2021

21. Nishimura Y, Fajgenbaum DC, Pierson SK, Iwaki N, Nishikori A, Kawano M, Nakamura N, Izutsu K, Takeuchi K, Nishimura MF, Maeda Y, Otsuka F, Yoshizaki K, Oksenhendler E, van Rhee F, Sato Y. Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease. American journal of hematology, 96:1241-1252, 2021

22. Munakata W, Tobinai K. Tirabrutinib hydrochloride for B-cell lymphomas. Drugs of today (Barcelona, Spain: 1998), 57:277-289, 2021

23. Maeshima AM, Taniguchi H, Hori Y, Ida H, Hosoba R, Makita S, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Izutsu K. Diagnostic utility and prognostic significance of the Ki-67 labeling index in diffuse large B-cell lymphoma transformed from follicular lymphoma: a study of 76 patients. Pathology international, 71:674-681, 2021

24. Suzuki T, Maruyama D, Miyagi-Maeshima A, Nomoto J, Tajima K, Ito Y, Hatta S, Yuda S, Makita S, Fukuhara S, Munakata W, Suzuki T, Taniguchi H, Izutsu K, Kobayashi Y, Tobinai K. Clinicopathological analysis of primary refractory diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy. Cancer medicine, 10:5101-5109, 2021

25.  Matsumoto M, Suzuki K, Kuroda J, Taniwaki M, Sunami K, Kosugi H, Ando K, Maruyama D, Tobinai K, Kher U, Farooqui M, Liao J, Marinello P, Matsuda K, Koh Y, Shimamoto T, Iida S. Pembrolizumab plus pomalidomide and dexamethasone for relapsed or refractory multiple myeloma (KEYNOTE-183): subgroup analysis in Japanese patients. International journal of hematology, 113:777-784, 2021

26. Ri M, Iida S, Maruyama D, Sakabe A, Kamei R, Nakashima T, Tohkin M, Osaga S, Tobinai K, Fukuhara N, Miyazaki K, Tsukamoto N, Tsujimura H, Yoshimitsu M, Miyamoto K, Tsukasaki K, Nagai H. HLA genotyping in Japanese patients with multiple myeloma receiving bortezomib: An exploratory biomarker study of JCOG1105 (JCOG1105A1). Cancer science, 112:5011-5019, 2021

27. Kagiyama Y, Fujita S, Shima Y, Yamagata K, Katsumoto T, Nakagawa M, Honma D, Adachi N, Araki K, Kato A, Inaki K, Ono Y, Fukuhara S, Kobayashi Y, Tobinai K, Kitabayashi I. CDKN1C-mediated growth inhibition by an EZH1/2 dual inhibitor overcomes resistance of mantle cell lymphoma to ibrutinib. Cancer science, 112:2314-2324, 2021

28. Nowakowski GS, Chiappella A, Gascoyne RD, Scott DW, Zhang Q, Jurczak W, Özcan M, Hong X, Zhu J, Jin J, Belada D, Bergua JM, Piazza F, Mócikova H, Molinari AL, Yoon DH, Cavallo F, Tani M, Yamamoto K, Izutsu K, Kato K, Czuczman M, Hersey S, Kilcoyne A, Russo J, Hudak K, Zhang J, Wade S, Witzig TE, Vitolo U . ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 39:1317-1328, 2021

29. Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT . Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. The Lancet. Oncology, 22:1403-1415, 2021