Department of Hematology

Kunihiro Tsukasaki, Sachiko Seo, Kensuke Narukawa, Rumiko Okamoto, Kota Ohashi, Chiharu Kobayashi

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 entity in WHO classification (version 2008). Our department focuses on early and late phases of clinical trials in collaboration with Research Center for Innovative Oncology and Japan Clinical Oncology Group (JCOG), respectively, especially on lymphoid malignancies.

Our Team and What We Do

The number of patients with newly diagnosed hematologic malignancies in our department is increasing, and approximately 290 patients with newly diagnosed hematological malignancies including non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, macroglobulinemia, acute leukemia, myelodysplastic syndrome, and chronic leukemia were cared this year (Table 1). Our department is currently providing routine chemotherapy as an outpatient service for an increasing number of relatively aged patients with hematological malignancies. All patients undergoing intensive chemotherapy and autologous peripheral blood hematopoietic stem cell transplantation (APBSCT) (Table 2) are managed in laminar airflow rooms at the designated ward on the eighth floor. Besides managing patients, our department also provides consultation 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, weekly joint conferences on lymphoid malignancies with expert pathologists and educational cytology conferences on bone marrow specimens are held. Joint morning journal clubs of our department and the Department of Breast and Medical Oncology are held on Mondays and Fridays.

Table 1. Number of patients

Table 2. Type of procedures

Research activities

Ancillary studies associated with retrospective case series and clinical trials at this department have been continuously conducted focusing on several kinds of hematological malignancies and their complications. Recently, a nation-wide survey of human T-lymphotropic virus type I (HTLV-1) associated adult T-cell leukemia-lymphoma (ATL) is ongoing by our department under a grant for Cancer Research from the Ministry of Health to elucidate the pathophysiology including geographical findings as compared to surveys from the 1980's to 1990's.

Clinical trials

Clinical trials on hematological malignancies performed by our department comprise protocols prepared in-house and participation in the Lymphoma Study Group of Japan Clinical Oncology Group- (JCOG-LSG), the Japan Adult Leukemia Study Group (JALSG), and others. Our 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 tri-weekly with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with newly diagnosed CD20+ diffuse large B cell lymphoma (DLBCL) (JCOG 0601) 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 melpharan, cyclophosphamide, etoposide, and dexamethasone (LEED) with APBSCT in patients with newly diagnosed poor risk CD20+ DLBCL (JCOG 0908); 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 transplant with untreated symptomatic myeloma (JCOG 1105); and a single armed phase III study of mLSG15 chemotherapy followed by allo-HSCT, comparing the results with historical control in JCOG 9801 of mLSG15 alone to evaluate the promising efficacy of allo-HSCT, possibly associated with a graft-versus-ATL effect, especially with the view of a comparison with intensive chemotherapy (JCOG 0907). A phase III study evaluating the efficacy of combination of interferon-alpha (IFN) and zidovudine (AZT) as compared to watchful-waiting for indolent ATL (JCOG 1111) is ongoing under the highly advanced medical technology assessment system because IFN and AZT are not covered for ATL by the National Health Insurance in Japan. A single armed phase III study of interim-PET response adapted switch-strategy from ABVD to ABVD/DE-BEACOP for advanced Hodgkin Lymphoma (JCOG 1305). A phase III study of watchful waiting versus rituximab as first-line treatment in patients with low tumor burden of advanced stage follicular lymphoma (JCOG 1411).

List of papers published in 2016

Journal

1.Nakai H, Tsukasaki K, Kyota K, Itatani T, Nihonyanagi R, Shinmei Y, Yasuoka S. Factors Related to Evacuation Intentions of Power-Dependent Home Care Patients in Japan. J Community Health Nurs, 33:196-208, 2016

2.Ogura M, Ishida T, Tsukasaki K, Takahashi T, Utsunomiya A. Effects of first-line chemotherapy on natural killer cells in adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. Cancer Chemother Pharmacol, 78:199-207, 2016

3.Seo S, Gooley TA, Kuypers JM, Stednick Z, Jerome KR, Englund JA, Boeckh M. Human Metapneumovirus Infections Following Hematopoietic Cell Transplantation: Factors Associated With Disease Progression. Clin Infect Dis, 63:178-185, 2016

4.Fenske TS, Ahn KW, Graff TM, DiGilio A, Bashir Q, Kamble RT, Ayala E, Bacher U, Brammer JE, Cairo M, Chen A, Chen Y-B, Chhabra S, D'Souza A, Farooq U, Freytes C, Ganguly S, Hertzberg M, Inwards D, Jaglowski S, Kharfan-Dabaja MA, Lazarus HM, Nathan S, Pawarode A, Perales M-A, Reddy N, Seo S, Sureda A, Smith SM, Hamadani M. Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation. Br J Haematol, 174:235-248, 2016

5.Morita K, Nakamura F, Taoka K, Satoh Y, Iizuka H, Masuda A, Seo S, Nannya Y, Yatomi Y, Kurokawa M. Incidentally-detected t(9;22)(q34;q11)/BCR-ABL1- positive clone developing into chronic phase chronic myeloid leukaemia after four years of dormancy. Br J Haematol, 174:815-817, 2016

6.Williams KM, Ahn KW, Chen M, Aljurf MD, Agwu AL, Chen AR, Walsh TJ, Szabolcs P, Boeckh MJ, Auletta JJ, Lindemans CA, Zanis-Neto J, Malvezzi M, Lister J, de Toledo Codina JS, Sackey K, Chakrabarty JLH, Ljungman P, Wingard JR, Seftel MD, Seo S, Hale GA, Wirk B, Smith MS, Savani BN, Lazarus HM, Marks DI, Ustun C, Abdel-Azim H, Dvorak CC, Szer J, Storek J, Yong A, Riches MR. The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis. Bone Marrow Transplant, 51:573-580, 2016

7.Omata Y, Nakamura S, Koyama T, Yasui T, Hirose J, Izawa N, Matsumoto T, Imai Y, Seo S, Kurokawa M, Tsutsumi S, Kadono Y, Morimoto C, Aburatani H, Miyamoto T, Tanaka S. Identification of Nedd9 as a TGF-beta-Smad2/3 Target Gene Involved in RANKL-Induced Osteoclastogenesis by Comprehensive Analysis. PLoS One, 11:e0157992, 2016

8.Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. J Clin Oncol, 34:4086-4093, 2016

9.Kanda J, Brazauskas R, Hu Z-H, Kuwatsuka Y, Nagafuji K, Kanamori H, Kanda Y, Miyamura K, Murata M, Fukuda T, Sakamaki H, Kimura F, Seo S, Aljurf M, Yoshimi A, Milone G, Wood WA, Ustun C, Hashimi S, Pasquini M, Bonfim C, Dalal J, Hahn T, Atsuta Y, Saber W. Graft-versus-Host Disease after HLA-Matched Sibling Bone Marrow or Peripheral Blood Stem Cell Transplantation: Comparison of North American Caucasian and Japanese Populations. Biol Blood Marrow Transplant, 22:744-751, 2016

10.Aoki J, Seo S, Kanamori H, Tanaka M, Fukuda T, Onizuka M, Kobayashi N, Kondo T, Sawa M, Uchida N, Iwato K, Icihnohe T, Atsuta Y, Yano S, Takami A. Impact of low-dose TBI on outcomes of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for AML. Bone Marrow Transplant, 51:604-606, 2016

Book

1.Seo S, Boeckh M. Respiratory viruses after hematopoietic cell transplantation. In: Stephen J. Forman, Robert S. Negrin, Joseph H. Antin, Frederick R (eds), Thomas'Hematopoietic Cell Transplantation, Fifth Edition, Wiley-Blackwell, pp 1112-1121, 2016