Annual Report 2017

Department of Hematology

Yosuke Minami, Sachiko Seo, Junichiro Yuda, Nobihiko Yamauti, Kenichi Miyamoto

Introduction

 The staff-physicians and residents of the Department of Hematology carry out clinical and research activities related to multidisciplinary treatment of patients with hematological malignancies which consist of more than 100 disease entity in the WHO classification. Our department focuses on early and late phases of clinical trials in collaboration with the Exploratory Oncology Research & Clinical Trial Center (EPOC) for Innovative Oncology on hematological malignancies.

Our 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 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 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, 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 pathophysi-ology including geographical findings as compared to previous surveys. We also carry out trans-lational 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. Our depart-ment 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 transplant 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) 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. 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, 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 research activities and develop new research for the improvement of treatment for patients with hematologic malignancies including non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, acute/chronic leukemia, myelodysplastic syndrome.

List of papers published in January 2017 - March 2018

Journal

 1. Kakiuchi S, Minami Y, Miyata Y, Mizutani Y, Goto H, Kawamoto S, Yakushijin K, Kurata K, Matsuoka H, Minami H. NANOG Expression as a Responsive Biomarker during Treatment with Hedgehog Signal Inhibitor in Acute Myeloid Leukemia. Int J Mol Sci, 18:2017

 2. Muffly L, Pasquini MC, Martens M, Brazauskas R, Zhu X, Adekola K, Aljurf M, Ballen KK, Bajel A, Baron F, Battiwalla M, Beitinjaneh A, Cahn JY, Carabasi M, Chen YB, Chhabra S, Ciurea S, Copelan E, D'Souza A, Edwards J, Foran J, Freytes CO, Fung HC, Gale RP, Giralt S, Hashmi SK, Hildebrandt GC, Ho V, Jakubowski A, Lazarus H, Luskin MR, Martino R, Maziarz R, McCarthy P, Nishihori T, Olin R, Olsson RF, Pawarode A, Peres E, Rezvani AR, Rizzieri D, Savani BN, Schouten HC, Sabloff M, Seftel M, Seo S, Sorror ML, Szer J, Wirk BM, Wood WA, Artz A. Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood, 130:1156-1164, 2017

 3. Ogimi C, Waghmare AA, Kuypers JM, Xie H, Yeung CC, Leisenring WM, Seo S, Choi SM, Jerome KR, Englund JA, Boeckh M. Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies. Clin Infect Dis, 64:1532-1539, 2017

 4. Cornell RF, D'Souza A, Kassim AA, Costa LJ, Innis-Shelton RD, Zhang MJ, Huang J, Abidi M, Aiello J, Akpek G, Bashey A, Bashir Q, Cerny J, Comenzo R, Diaz MA, Freytes C, Gale RP, Ganguly S, Hamadani M, Hashmi S, Holmberg L, Hossain N, Kamble RT, Kharfan-Dabaja M, Kindwall-Keller T, Kyle R, Kumar S, Lazarus H, Lee C, Maiolino A, Marks DI, Meehan K, Mikhael J, Nath R, Nishihori T, Olsson RF, Ramanathan M, Saad A, Seo S, Usmani S, Vesole D, Vij R, Vogl D, Wirk BM, Yared J, Krishnan A, Mark T, Nieto Y, Hari P. Maintenance versus Induction Therapy Choice on Outcomes after Autologous Transplantation for Multiple Myeloma. Biol Blood Marrow Transplant, 23:269-277, 2017

 5. Chen YB, Wang T, Hemmer MT, Brady C, Couriel DR, Alousi A, Pidala J, Urbano-Ispizua A, Choi SW, Nishihori T, Teshima T, Inamoto Y, Wirk B, Marks DI, Abdel-Azim H, Lehmann L, Yu L, Bitan M, Cairo MS, Qayed M, Salit R, Gale RP, Martino R, Jaglowski S, Bajel A, Savani B, Frangoul H, Lewis ID, Storek J, Askar M, Kharfan-Dabaja MA, Aljurf M, Ringden O, Reshef R, Olsson RF, Hashmi S, Seo S, Spitzer TR, MacMillan ML, Lazaryan A, Spellman SR, Arora M, Cutler CS. GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes. Bone Marrow Transplant, 52:400-408, 2017

 6. Yuda J, Miyamoto T, Odawara J, Ohkawa Y, Semba Y, Hayashi M, Miyamura K, Tanimoto M, Yamamoto K, Taniwaki M, Akashi K. Persistent detection of alternatively spliced BCR-ABL variant results in a failure to achieve deep molecular response. Cancer Sci, 108:2204-2212, 2017

 7. Sahoo F, Hill JA, Xie H, Leisenring W, Yi J, Goyal S, Kimball LE, Lee I, Seo S, Davis C, Pergam SA, Flowers ME, Liaw KL, Holmberg L, Boeckh M. Herpes Zoster in Autologous Hematopoietic Cell Transplant Recipients in the Era of Acyclovir or Valacyclovir Prophylaxis and Novel Treatment and Maintenance Therapies. Biol Blood Marrow Transplant, 23:505-511, 2017

 8. Vrooman LM, Millard HR, Brazauskas R, Majhail NS, Battiwalla M, Flowers ME, Savani BN, Akpek G, Aljurf M, Bajwa R, Baker KS, Beitinjaneh A, Bitan M, Buchbinder D, Chow E, Dandoy C, Dietz AC, Diller L, Gale RP, Hashmi SK, Hayashi RJ, Hematti P, Kamble RT, Kasow KA, Kletzel M, Lazarus HM, Malone AK, Marks DI, O'Brien TA, Olsson RF, Ringden O, Seo S, Steinberg A, Yu LC, Warwick A, Shaw B, Duncan C. Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age. Biol Blood Marrow Transplant, 23:1327-1334, 2017

 9. El-Jawahri A, Chen YB, Brazauskas R, He N, Lee SJ, Knight JM, Majhail N, Buchbinder D, Schears RM, Wirk BM, Wood WA, Ahmed I, Aljurf M, Szer J, Beattie SM, Battiwalla M, Dandoy C, Diaz MA, D'Souza A, Freytes CO, Gajewski J, Gergis U, Hashmi SK, Jakubowski A, Kamble RT, Kindwall-Keller T, Lazarus HM, Malone AK, Marks DI, Meehan K, Savani BN, Olsson RF, Rizzieri D, Steinberg A, Speckhart D, Szwajcer D, Schoemans H, Seo S, Ustun C, Atsuta Y, Dalal J, Sales-Bonfim C, Khera N, Hahn T, Saber W. Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation. Cancer, 123:1828-1838, 2017

10. Boeckh M, Stevens-Ayers T, Travi G, Huang ML, Cheng GS, Xie H, Leisenring W, Erard V, Seo S, Kimball L, Corey L, Pergam SA, Jerome KR. Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia. J Infect Dis, 215:1514-1522, 2017

11. Seo S, Waghmare A, Scott EM, Xie H, Kuypers JM, Hackman RC, Campbell AP, Choi SM, Leisenring WM, Jerome KR, Englund JA, Boeckh M. Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality. Haematologica, 102:1120-1130, 2017

12. Minami Y, Minami H, Miyamoto T, Yoshimoto G, Kobayashi Y, Munakata W, Onishi Y, Kobayashi M, Ikuta M, Chan G, Woolfson A, Ono C, Shaik MN, Fujii Y, Zheng X, Naoe T. Phase I study of glasdegib (PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies. Cancer Sci, 108:1628-1633, 2017

13. Miyamoto K, Ito A, Wakabayashi M, Eba J, Arai Y, Nishiyama H, Sugimoto M, Yamashita R, Kakehi Y. A Phase III trial of a single early intravesical instillation of pirarubicin to prevent bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma (JCOG1403, UTUC THP Phase III). Jpn J Clin Oncol, 48:94-97, 2018

14. Takahashi N, Tauchi T, Kitamura K, Miyamura K, Saburi Y, Hatta Y, Miyata Y, Kobayashi S, Usuki K, Matsumura I, Minami Y, Usui N, Fukuda T, Takada S, Ishikawa M, Fujimaki K, Gomyo H, Sasaki O, Ohishi K, Miyake T, Imai K, Suzushima H, Mitsui H, Togitani K, Kiguchi T, Atsuta Y, Ohtake S, Ohnishi K, Kobayashi Y, Kiyoi H, Miyazaki Y, Naoe T. Deeper molecular response is a predictive factor for treatment-free remission after imatinib discontinuation in patients with chronic phase chronic myeloid leukemia: the JALSG-STIM213 study. Int J Hematol, 107:185-193, 2018

15. Okada M, Imagawa J, Tanaka H, Nakamae H, Hino M, Murai K, Ishida Y, Kumagai T, Sato S, Ohashi K, Sakamaki H, Wakita H, Uoshima N, Nakagawa Y, Minami Y, Ogasawara M, Takeoka T, Akasaka H, Utsumi T, Uike N, Sato T, Ando S, Usuki K, Mizuta S, Hashino S, Nomura T, Shikami M, Fukutani H, Ohe Y, Kosugi H, Shibayama H, Maeda Y, Fukushima T, Yamazaki H, Tsubaki K, Kukita T, Adachi Y, Nataduka T, Sakoda H, Yokoyama H, Okamoto T, Shirasugi Y, Onishi Y, Nohgawa M, Yoshihara S, Morita S, Sakamoto J, Kimura S. Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment. Clin Lymphoma Myeloma Leuk, 18:353-360.e1, 2018