Management of Hematological Cancer in Older People. Ulrich Wedding Riccardo A. Audisio Editors

Transcription

1

2 Management of Hematological Cancer in Older People Ulrich Wedding Riccardo A. Audisio Editors 123

3 Management of Hematological Cancer in Older People

4

5 Ulrich Wedding Riccardo A. Audisio Editors Management of Hematological Cancer in Older People

6 Editors Ulrich Wedding Department of Palliative Care University Hospital Jena Jena, Thüringen Germany Riccardo A. Audisio St Helens Teaching Hospital University of Liverpool St Helens United Kingdom ISBN ISBN (ebook) DOI / Springer London Heidelberg New York Dordrecht Library of Congress Control Number: Springer-Verlag London 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (

7 Contents 1 Hematological Malignancies in the Elderly: The Epidemiological Perspective Alberto Quaglia, Marina Vercelli, and Roberto Lillini, AIRTUM Working Group 2 Anemia, Fatigue and Aging Lodovico Balducci 3 Myelodysplastic Syndromes in Older Patients Reinhard Stauder 4 Acute Myeloid Leukemia Heidi D. Klepin and Timothy S. Pardee 5 Chronic Myelogeneous Leukemia Andreas Hochhaus and Susanne Saussele 6 Myeloproliferative Neoplasms Farah Shariff and Claire Harrison 7 Chronic Lymphocytic Leukemia (CLL) Valentin Goede and Michael Hallek 8 Indolent Lymphomas in Older Patients Andreas Viardot and Christian Buske 9 The Challenge of Treating Elderly Patients with Mantle Cell Lymphoma Simone Ferrero and Martin Dreyling 10 Hodgkin Lymphoma in the Elderly Paul Fields 11 Diffuse Large B-Cell Non-Hodgkin s Lymphoma (DLBCL- NHL) Nils Winkelmann and Ulrich Wedding v

8 vi Contents 12 Multiple Myeloma Roberto Mina and Antonio Palumbo 13 Geriatric Assessment Martine Extermann 14 Nursing Issues Corien M. Eeltink, Angelina Beumer-Grootenhuis, and Carolien Burghout 15 General Considerations on Treatment in Older Patients with Hematological Malignancies Pierre Soubeyran, Camille Chakiba, and Anne-Sophie Michallet 16 General Consideration on Radiotherapy in Older Patients with Hematological Malignancies Youlia M. Kirova 17 Supportive Care in Older Patients with Hematological Malignancies Karin Jordan, Berit Jordan, Camilla Leithold, and Jörn Rüssel 18 Patients Reported Outcome/Quality of Life Barbara Deschler 19 Palliative Care in Elderly Patients with Hematological Malignancies Ulrich Wedding Index

9 Contributors Riccardo A. Audisio, MD, FRCS St Helens Teaching Hospital, University of Liverpool, St Helens, UK Lodovico Balducci, MD H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, FL, USA Angelina Beumer, MD Department of Oncology, Deventer Ziekenhuis, Ziekenhuis, The Netherlands Angelina Beumer-Grootenhuis, RN Department of Oncology, Deventer Ziekenhuis, Deventer, The Netherlands Carolien Burghout, RN, M ANP Department of Haematology, Jeroen Bosch Hospital, s-hertogenbosch, The Netherlands Christian Buske, MD Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research, University Hospital Ulm, Ulm, Germany Camille Chakiba, MD Department of Medical Oncology, Institut Bergonié, Bordeaux Cedex, France Site de Recherche Intégrée sur le Cancer, BRIO (Bordeaux Recherche Intégrée Oncologie), Bordeaux Cedex, France Barbara Deschler, MD Interdisciplinary Clinical Trials Office, Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany Department of Hematology/Oncology, University of Freiburg Medical Center, Freiburg, Germany Martin Dreyling, MD, PhD Department of Medicine III, University Hospital Großhadern/LMU München, Munich, Germany Corien M. Eeltink, RN, MA, ANP Department of Haematology, VU University Medical Center, Amsterdam, Netherlands vii

10 viii Contributors Martine Extermann Moffitt Cancer Center, University of South Florida, Tampa, FL, USA Simone Ferrero, MD Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy Paul Fields, MD Department of Haematology, Guy s and St Thomas, and Kings College Hospitals, Kings Health Partners AHSC, London, UK Valentin Goede, MD German CLL Study Group (GCLLSG), Department of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, Cologne, Germany Department of Geriatric Medicine and Research, St. Marien Hospital and University of Cologne, Cologne, Germany Michael Hallek, MD, PhD German CLL Study Group (GCLLSG), Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University of Cologne, Cologne, Germany Cluster of Excellence Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Cologne, Germany Claire Harrison, MD, DM, FRCP, FRCPath Department of Haematology, Guy s and St Thomas NHS Foundation Trust, Great Maze Pond, London, UK Andreas Hochhaus, Prof. Dr Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany Berit Jordan, MD Department of Neurology, University Hospital Halle (Saale), Halle (Saale), Germany Karin Jordan, MD Department of Hematology/Oncology, Universitätsklinikum Halle (Saale), Halle (Saale), Germany Youlia M. Kirova, MD Radiation Oncology, Institut Curie, Paris, France Heidi D. Klepin, MD, MS Department of Internal Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA Camilla Leithold, MSc Department of Hematology and Oncology, University Hospital Halle (Saale), Halle (Saale), Germany Roberto Lillini, PHD, AIRTUM Working Group IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy Department of Sociology, University of Milan-Bicocca, Milan, Italy Anne-Sophie Michallet, MD Department of Hematology, Hôpital Lyon-Sud, Hospices Civils de Lyon, Lyon, France

11 Contributors ix Roberto Mina, MD Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino, Italy Antonio Palumbo, MD Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino, Italy Timothy S. Pardee, MD, PhD Department of Internal Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA Alberto Quaglia, MD Liguria Region Cancer Registry, Descriptive Epidemiology Unit, IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy Jörn Rüssel, MD Department of Hematology and Oncology, University Hospital Halle (Saale), Halle (Saale), Germany Susanne Saussele, MD III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim, der Universität Heidelberg, Mannheim, Germany Farah Shariff, MD, MBBS, BSc (Hons), MRCP Department of Haematology, Guy s and St Thomas NHS Foundation Trust, Great Maze Pond, London, UK Pierre Soubeyran, MD Department of Medical Oncology, Institut Bergonié, Bordeaux Cedex, France Site de Recherche Intégrée sur le Cancer, BRIO (Bordeaux Recherche Intégrée Oncologie), Bordeaux Cedex, France Université Bordeaux, Segalen, France Reinhard Stauder, MD, MSc Department of Internal Medicine V (Haematology and Oncology), Innsbruck Medical University, Innsbruck, Austria Marina Vercelli, PHD Department of Health Sciences, University of Genoa, Genoa, Italy Andreas Viardot, MD Department of Internal Medicine III, Universitätsklinikum Ulm, Ulm, Germany Ulrich Wedding, MD Department of Palliative Care, University Hospital Jena, Jena, Thüringen, Germany Nils Winkelmann, MD Department of Internal Medicine II, Department of Hematology and Medical Oncology, Jena University Hospital, Jena, Germany

12 Chapter 1 Hematological Malignancies in the Elderly: The Epidemiological Perspective Alberto Quaglia, Marina Vercelli, and Roberto Lillini, AIRTUM Working Group Deceased AIRTUM Working Group: R.T. Alto Adige (Guido Mazzoleni), R.T. Trento (Silvano Piffer), R.T. Friuli-Venezia Giulia (Diego Serraino), R.T. Veneto (Sandro Tognazzo), R.T. Mantova (Paolo Ricci), R.T. ASL Milano (Luigi Bisanti), R.T. Lombardia Varese (Paolo Crosignani), R.T. Brescia (Michele magoni), R.T. Como (Gemma Gola), R.T. Sondrio (Maria Eugenia Sanoja Gonzalez), R.T. Piemonte Torino (Roberto Zanetti), R.T. Piemonte Biella (Adriano Giacomin), R.T. Liguria Genova (Marina Vercelli), R.T. Parma (Maria Michiara), R.T. Reggio Emilia (Lucia Mangone), R.T. Modena (Massimo Federico), R.T. Ferrara (Stefano Ferretti), R.T. Romagna (Fabio Falcini), R.T. Toscano (Adele Caldarella), R.T. Macerata (Susanna Vitarelli), R.T. Umbria (Francesco La Rosa), R.T. Latina (Fabio Pannozzo), R.T. Sassari (Ornelia Sechi), R.T. Nuoro (Mario Usala), R.T. Salerno (Luigi Cremone), R.T. Catanzaro (Antonella Sutera Sardo), R.T. Palermo (Francesco Vitale), R.T. Trapani (Giuseppina Candela), R.T. Catania-Messina (Salvatore Sciacca), R.T. Siracusa (Francesco Tisano), R.T. Ragusa (Rosario Tumino) M. Vercelli, PHD (*) Department of Health Sciences, University of Genoa, Italy, Genoa, Italy marina.vercelli@unige.it R. Lillini, PHD IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy Department of Sociology, University of Milan-Bicocca, Milan, Italy Springer-Verlag London 2015 U. Wedding, R.A. Audisio (eds.), Management of Hematological Cancer in Older People, DOI / _1 1

13 2 A. Quaglia et al. Abstract In the more developed countries the total number of new cases with a hematological tumour was 415,433 for all ages, whilst 188,654 occurred in people aged 70 or more years, representing the 45 % of total cases, equally divided into two sexes. The most these malignancies is closely linked to age and incidence rates increased exponentially after 50 years of age. Aetiology of hematological tumours is largely unknown. However the basic causal mechanism could be a decline in adaptive immunity, strongly related with individual age. In addition to such immunodeficiency, some specific risk factors have been found: viral infections, overweight and obesity (particularly for non- Hodgkin s lymphomas NHL), ionising radiation and chemical compounds (particularly for leukemia). Moreover, it must to be taken into account that mortality and survival, more specifically in the elderly, are influenced negatively by socio- economic deprivation. Considering geographical distribution, substantial variations in incidence and mortality across the world were observed. Incidence of younger and older adults was for all hematological malignancies higher in more developed countries. As regards mortality, younger people showed rates higher in developing countries, while the elderly in Western and developed areas. The epidemic growth of NHL incidence was not finished in the first decade of 2000, even if in Italian and US old populations the rates started leveling off. Unlike incidence, mortality was descending in the elderly. Leukemia incidence trends were very often stable or weakly growing, without any tendency to decrease, but for leukemia mortality it was possible to highlight an encouraging general picture with rates often decreasing. The elderly had always survival rates lower than those of middle aged adults. The prognostic disadvantage was larger at 1 than 5 years from diagnosis. The gap was smaller for NHL and acute myeloid leukemia, whereas the difference in survival was much larger for chronic myeloid leukemia and Hodgkin s lymphoma. Summarizing, elderly patients had a marked prognostic disadvantage with respect younger adults. However, if an elderly subject survives the first period immediately after detection and overcomes the first difficulties of access to healthcare, experiences a prognosis similar to that of a younger patient. Keywords Hematological tumours Aetiology Descriptive epidemiology Elderly Incidence Mortality Survival Trend Introduction Hematological malignancies are a heterogeneous group of tumours arising from lymphatic system and bone marrow. They are divided into three groups: leukaemia, lymphomas and plasma cells malignancies (multiple myeloma) and in 2008 in the world they accounted for 7 % of overall newly diagnosed cases and deaths, considering both sexes [ 1 ]. In the more developed countries for all ages the total number of new cases diagnosed with a hematological neoplasm was 415,433, whilst 188,654 occurred in people aged 70 or more years, representing 45 % of total hematological tumours, equally

14 1 Hematological Malignancies in the Elderly: The Epidemiological Perspective 3 Incidence Men Women 58 % 1 % 16 % 8 % 17 % HL 70+ Leukemias 70+ MM 70+ NHL 70+ HEM % 1 % 16 % 10 % 22 % HL 70+ Leukemias 70+ MM 70+ NHL 70+ HEM 0 69 Men Mortality Women 42 % 1 % 20 % 25 % 12 % HL 70+ Leukemias 70+ MM 70+ NHL 70+ HEM % 25 % 1 % 26 % 15 % HL 70+ Leukemias 70+ MM 70+ NHL 70+ HEM 0 69 Fig. 1.1 Hematopoietic system cancers: incidence and mortality in the aged 70 years and more vs. the less than 70 years ones by site and gender (proportion per 100). HL Hodgkin s Lymphoma, MM Multiple Myeloma, NHL Non - Hodgkin Lymphomas, HEMO Hematological Tumours divided into two sexes. As most cancers also some tumours of this group of malignancies is closely linked to age and its incidence rates increase exponentially after 50 years of age. In the more developed macro-areas, considering all the hematological tumours the number of incident cases in the elderly ( 70 years) accounted for 7 % in men and 6 % in women. Figure 1.1 show the incident cases of hematological tumours by broad age groups: in younger men (0 69 years) the yearly diagnosed new cases were 58 %, while the single entities for elderly accounted for 17, 16, 8 and 1 % in NHL, leukaemia, MM and HL respectively; in women the same values were 51 % for the younger, with the single entities accounting for 22, 16, 10 and 1 %. The percentages of haematopoietic tumours increased strikingly in the elderly moving to mortality: 42 % of deaths occurred in younger men, 58 % in elderly men, while 33 % in younger women and even 67 % in elderly ones. In older men the single entities accounted for 25, 20, 12 and 1 % in leukaemia, NHL, MM and HL respectively, while in women the same values were 26, 25, 15 and 1 % [ 1 ]. Aetiology Development of Hematological Tumours Is Favoured by Aging Process Aetiology of hematological tumours is up to now largely unknown. Several risk factors have been found in epidemiological studies and some associations have been identified and assessed, even if the etiologic factors do not account for a great number of incident cases. Moreover, it must be remind to distinguish

15 4 A. Quaglia et al. the natural history of hematological tumours occurring during childhood, adulthood, especially in the elderly. At this regard it is important to consider the latency time between the exposure to carcinogen, or more generally to the risk, and the cancer development. In any case, for most cases of hematological tumours it is impossible to find a precise genetic or environmental cause. In fact, several genetic disorders or environmental situations have been identified as risk factors, but they constitute only a small proportion of all hematological cases in the elderly [ 2, 3 ]. Leukaemia and lymphomas, like other cancers, start to grow up owing to the combination of environmental risk factors acting along with genetic susceptibilities. The most general mechanism which lead to the development of hematopoietic tumours is the lack of the equilibrium between the renewal and death of blood cells. During the lifespan, after the early development of hematological system, a balance between the renewal and death of blood cells begins. However, even if bone marrow is the tissue with the highest frequency of proliferation of stem cells, as other tissues, it must undergo ageing and its negative effects. The balance between cell progenitors and differentiated elements has the tendency to go off during aging, because, B lymphocytes in particular decrease their production [ 4, 5 ]. It is probably that the mechanism of senescence lead to a decline in B cell production, as a phenomenon already fixed in blood cells progenitors. In addition, hematopoietic cells begin to age and lose their physiological functions, with the alterations of the expression of some genes devoted to check the healthy status of DNA. Summarising, bone marrow and hematological system lose their capability to check for homeostasis and to repair DNA damages owing to ageing [ 6 ]. The impairment of progenitors involves principally the lymphoid compartment and, to a lesser extent, the proliferation of the myeloid cell line. In addition to the lost ability of cells to differentiate, some authors have found that also the environment of bone marrow, where the progenitors develop, changes its physiological conditions. Owing to the close relationship between haematic cells and the support tissue where they proliferate and differentiate, the physiological status is completely dependent by the stromal elements of bone marrow. All these hematological shortcomings lead to a decline in adaptive immunity and are strongly related with the individual s age [ 7 9 ]. Immunosuppression Both quantitative (the decrease of differentiated lymphocytes) and qualitative (compromised quality of stromal functions) defects cause a decline of all immune system [ 10, 11 ]. Such immunosuppression has been confirmed by some analyses which have studied in wide cohort of patients the correlation between immunodeficiency (congenital or acquired) and the probability to develop hematological cancers. At this proposal, is of particular interest a study which has shown that about