Handbook of Acute Leukemia

100 Pages·2016·1.04 MB·English

by  Wolfgang Hiddemann (eds.)

Wolfgang Hiddemann
Editor
Handbook of
Acute Leukemia
Editor
Wolfgang Hiddemann
Handbook of
Acute Leukemia
Editor
Wolfgang Hiddemann, MD, PhD
Department of Medicine III
University of Munich
Munich, Germany
Handbook of
Acute Leukemia
Editor Contributors
Wolfgang Hiddemann, MD, PhD Michael Fiegl, MD
Department of Medicine III Wolfgang Hiddemann, MD, PhD
University of Munich Klaus Metzeler, MD
Munich Karsten Spiekermann, MD
Germany Marion Subklewe, MD
ISBN 978-3-319-26770-8 ISBN 978-3-319-26772-2 (eBook)
DOI 10.1007/978-3-319-26772-2
© Springer International Publishing Switzerland 2016
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Project editor: Laura Hajba
Contents
Editor and author biographies vii
Abbreviations xi
1 Introduction 1
Wolfgang Hiddemann
Reference 2
2 Epidemiology, pathogenesis, and etiology
of acute leukemia 3
Michael Fiegl
Epidemiology and incidence 3
Biology and pathogenesis of acute leukemia 4
Etiology of acute leukemia 7
References 11
3 Clinical manifestations and diagnosis 15
Klaus Metzeler
Clinical presentation of acute leukemia 15
Diagnostic testing and criteria 16
Differential diagnosis 20
Additional work-up for patients with acute leukemias 21
References 22
4 Diagnostic criteria, classification, and prognosis
of acute leukemias 25
Klaus Metzeler
Diagnostic criteria and classification of acute myeloid leukemia 25
Diagnostic criteria and classification of lymphoblastic leukemias 30
Diagnostic criteria and classification of acute leukemias of
ambiguous lineage 33
Prognostic factors in acute myeloid leukemia 34
Prognostic factors in acute lymphoblastic leukemia 37
References 38
v
vI • CONTENTS
5 Therapeutic management of acute myeloid leukemia 41
Michael Fiegl
Overview of treatment options 41
Treatment by phase 41
Resistant and relapsed leukemia 47
Treatment of the medically unfit and elderly patient 48
References 49
6 Therapeutic management of acute
promyelocytic leukemia 53
Karsten Spiekermann
Overview of treatment options 53
Treatment by risk group and phase 54
References 63
7 Therapeutic management of acute
lymphoblastic leukemia 65
Karsten Spiekermann
General approach for management of acute lymphoblastic leukemia 65
Prognostic factors and risk-adapted therapy 65
Clinical trials supporting current treatment algorithms in first-line therapy 66
Overview of treatment options 69
Treatment by phase 72
References 74
8 Future outlook for acute leukemias 77
Marion Subklewe
Emerging therapies in acute leukemias 77
Molecular-targeted therapies 77
Allogeneic hematopoietic stem cell transplantation 79
Antibody-based immunotherapy for acute leukemia 82
Chimeric-antigen receptor T cells 86
Checkpoint inhibitors in acute leukemia 89
Conclusions and future outlook 90
References 90
Editor and author biographies
Wolfgang Hiddemann, MD, PhD, is Professor of Medicine and Director
of the Department of Internal Medicine III at the University of Munich,
Germany. Dr Hiddemann is best known for his research on the patho-
genesis of acute leukemias, and clinical trials in acute leukemias and
malignant lymphomas. He is head of the German AML Cooperative Group
(AMLCG), the German Low Grade Lymphoma Study Group (GLSG), and
founding chairman of the European Mantle-Cell-Lymphoma Network.
He is an active member of the editorial boards of several international
journals and has been a member of the Steering Committees for the
German Society of Hematology and Oncology and the German Cancer
Aid. Dr Hiddemann has published nearly 600 scientific articles address-
ing various aspects of research in malignant lymphomas and acute leu-
kemias. He has been awarded honorary memberships of the Hungarian
Society of Hematology and Oncology and of the South African Society for
Hematology. He also received the Honorary Medal of the Polish Society
for Internal Medicine. In 2003, he was awarded the Charles Burpbacher
Lectureship in Zürich, Switzerland, and in the same year the Emil Frei
Leukemia Lectureship, Harvard University, Boston. He has also received
the Jacqueline Seroussi Foundation Scientific Award.
Michael A Fiegl, MD, is a hematologist and oncologist in the Department
of Internal Medicine III at the Klinikum der Universität München,
Germany. After attending medical schools in Berlin and Munich, Germany,
he completed his clinical training at Munich under the supervision of
Prof Dr Wolfgang Hiddemann. He then extended his scientific experi-
ence during his postdoctoral fellowship at the UT MD Anderson Cancer
Center in Houston, TX, USA under Prof Dr Michael Andreeff. His work
has primarily focused on acute myeloid leukemia (AML) both clinically
and scientifically ever since; besides basic research on AML and the
vII
vIII • EDITOR AND AUTHOR BIOGRAPHIES
bone marrow microenvironment, he has collaborated on several large
multicenter trials on AML.
Klaus Metzeler, MD, is a senior physician in the Department of Internal
Medicine, Hematology and Oncology at the University of Munich,
Germany. He completed his clinical training at the University of Munich
and studied leukemia genetics as a research fellow at The Ohio State
Comprehensive Cancer Center, Columbus, OH, USA. As a clinician-
scientist, his research is focused on developing novel diagnostic tools,
prognostic and predictive biomarkers, and ultimately more effective
treatment approaches for patients with myeloid neoplasia. Dr Metzeler
has co-authored over 50 scientific publications on myeloid leukemias.
Karsten Spiekermann, MD, is a hematologist and oncologist in the
Department of Internal Medicine III at the Klinikum der Universität
München, Germany. After attending medical school in Hannover,
Germany, he completed his clinical training in Göttingen and Munich
under the supervision of Prof Dr Wolfgang Hiddemann. He received
his postdoc education at the Manx-Planck Institute for Biochemistry in
Martinsried (Germany) under the supervision of Prof Dr Axel Ullrich.
The focus of his work was the pathogenesis, diagnostics, and treatment
optimization of acute and chronic leukemias.
Marion Subklewe, MD, is an attending physician and Professor of Medicine
with a focus on immunotherapy at the Department of Hematology/
Oncology at the Ludwig-Maximilians-University Munich, Germany. She
is head of the diagnostic flow cytometry unit within the Laboratory of
Leukemia Diagnostics within the Department of Hematology/Oncology
and head of the clinical cooperation group ‘Immunotherapy’, Helmholtz
Zentrum Munich. Prof Subklewe’s interests center on translational medi-
cine. Several preclinical immunotherapeutic approaches were successfully
translated into early clinical trials focusing on T-cell recruiting vaccines
and antibody concepts. She is active in several clinical studies, serving
as principal investigator for clinical trials in acute myeloid leukemia
(AML) and acute lymphoblastic leukemia (ALL), and as an investigator
EDITOR AND AUTHOR BIOGRAPHIES • Ix
and steering committee member of the AML Cooperative Group. Prof
Subklewe is involved in the Bavarian Immunotherapy Network, the
Helmholtz Alliance for Immunotherapy, the interdisciplinary CRC 1243
in Cancer Evolution, the German Consortium for Translational Cancer
Research (DKTK), the international Graduate School ‘Immunotargeting of
Cancer’ and the Else-Kröner Forschungskolleg ‘Cancer Immunotherapy’.
Abbreviations
ACT Adoptive cellular therapy
ADC Antibody drug conjugate
AIDA ATRA plus idarubicin
AIDS Acquired immune deficiency syndrome
ALL Acute lymphocytic leukemia
AML Acute myeloid leukemia
AML-MRC AML with myelodysplasia-related changes
ANC Absolute neutrophil count
APL Acute promelocytic leukemia
AraC Anthracycline
ATO Arsenic trioxide
ATRA All-trans retinoic acid
BCP-ALL B-cell precursor ALL
BID Twice daily
BiTE Bispecific T-cell engager
BM Bone marrow
CALGB Cancer and Leukemia Group B
CARTs Chimeric antigen receptor T cells
CBF Core binding factor
CCI Charlson Comorbidity index
CI Continuous infusion
CIR Cumulative incidence of relapse
CML Chronic myeloid leukemia
CML-BP CML in blast phase
CMML Chronic myelomonocytic leukemia
CNS Central nervous system
CR Complete response/remission
CSF Cerebrospinal fluid
CT Computed tomography
CTLA-4 Cytotoxic T lymphocyte-associated antigen 4
DA Daunorubicin
DART Dual affinity retargeting molecule
xI