MYELOID LEUKEMIA – CLINICAL DIAGNOSIS AND TREATMENT Edited by Steffen Koschmieder and Utz Krug Myeloid Leukemia – Clinical Diagnosis and Treatment Edited by Steffen Koschmieder and Utz Krug Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Ivana Zec Technical Editor Teodora Smiljanic Cover Designer InTech Design Team Image Copyright Eraxion , 2011. DepositPhotos First published December, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Myeloid Leukemia – Clinical Diagnosis and Treatment, Edited by Steffen Koschmieder and Utz Krug p. cm. ISBN 978-953-307-886-1 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Chapter 1 Treatment of Chronic Myeloid Leukaemia: Current Practice and Future Prospects 1 Daniela M. Zisterer Chapter 2 The Value of Molecular Response in Chronic Myeloid Leukemia: The Present and the Future 25 Lorenzo Falchi, Viviana Appolloni, Lucia Ferranti and Anna Marina Liberati Chapter 3 Role of High Dose Imatinib in BCR/ABL pos /Ph pos CML 53 Andreas L. Petzer and Holger Rumpold Chapter 4 Therapeutic Drug Monitoring of Imatinib for Chronic Myeloid Leukemia Patients 71 Naoto Takahashi and Masatomo Miura Chapter 5 Drug- Induced Pneumonitis: A Rare Complication of Imatinib Mesylate Therapy in Patients with Chronic Myeloid Leukemia 85 O.V. Lazareva and A.G. Turkina Chapter 6 Towards the Cure of CML by the Molecular Approach Strategy 95 Michele Cea, Antonia Cagnetta, Marco Gobbi and Franco Patrone Chapter 7 Therapy of Acute Myeloid Leukemia 111 Jean El-Cheikh and Roberto Crocchiolo Chapter 8 Diagnosis of Acute Myeloid Leukaemia 129 Anca Bacârea Chapter 9 Diagnostic Approach in Acute Myeloid Leukemias in Line with WHO 2008 Classification 157 Manu Goyal and K. Gayathri VI Contents Chapter 10 Clinical and Biological Relevance of Gene Expression Profiling in Acute Myeloid Leukemia 197 Alicja M. Gruszka and Myriam Alcalay Chapter 11 Clinical Characteristics of Acute Myeloid Leukemia with t(8;21) in Japan and Western Countries 211 Hiroto Narimatsu Chapter 12 Acute Promyelocytic Leukemia Lacking the Classic Translocation t(15;17) 219 Jad J. Wakim and Carlos A. Tirado Chapter 13 Treating the Elderly Patient with Acute Myelogenous Leukemia 235 Mehrdad Payandeh, Mehrnosh Aeinfar and Vahid Aeinfar Chapter 14 Prognosis and Survival in Acute Myelogenous Leukemia 259 Muath Dawod and Amr Hanbali Chapter 15 Bacillus cereus Sepsis in the Treatment of Acute Myeloid Leukemia 281 Daichi Inoue and Takayuki Takahashi Preface Myeloid leukemias have been studied for decades, and considerable progress has been made in the elucidation of critical pathogenetic factors including transcription factor networks and signaling pathways and in the diagnosis and treatment of these leukemias. However, while the prognosis of a fraction of patients (particularly those with chronic myeloid leukemia in chronic phase) has improved dramatically with the advent of novel rationally designed therapies, the prognosis of many other patients (i.e. with most subtypes of acute myeloid leukemia) has not improved to the same degree. Futhermore, molecular targeted therapies are expensive and are not readily available in all parts of the world. The intention of this book is to provide a global scope on these issues. Following an open call, authors were invited to propose topics and send in an abstract of the chapter they wanted to contribute. After selection of appropriate abstracts, full chapters were provided and reviewed. Revised chapters were again reviewed and final chapters selected for publication. The topics of the present book focus on clinical aspects of myeloid leukemias and cover the following: Diagnosis and treatment of chronic myeloid leukemia (CML), including standard and high dose imatinib as well as second generation inhibitors Response Monitoring in CML with a special focus on current molecular monitoring Rare adverse events during TKI therapy (drug-induced pneumonitis) Novel therapeutic approaches towards a potential cure of CML Diagnosis and treatment of acute myeloid leukemia (AML), in line with the WHO 2008 classification Gene Expression Profiling in AML Potential ethnic differences in the clinical characteristics of AML Acute promyelocytic Leukemia lacking the classic translocation (15;17) Treatment of Elderly Patients with AML Prognosis and Survival in AML Complications of Treatment in AML, including Bacillus cereus sepsis X Preface Each chapter is a sole-standing publication that reflects each author´s interpretation of the data. However, the unifying theme is myeloid leukemia. Thus, the book displays a multi-facetted picture of our current understanding of the clinical implications for diagnosing and treating patients with myeloid leukemias. In addition, the open access structure of the book will guarantee wide-spread access even in cases where resources required for subscription to more expensive scientific journals or books are limited. We encourage the readers to send their comments. This is an exciting new way of discussing science and to support the effort of increasing the alertness and education of patients and physicians all around the globe. Prof. Dr. Steffen Koschmieder Department of Medicine (Oncology, Hematology, and Stem Cell Transplantation) at the University of Aachen, Germany Dr. Utz Krug Department of Medicine (Hematology, Oncology, Hemostaseology, and Pulmonology) at the University of Münster, Germany [...]... diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS) Blood, Vol 116, No 19 (November 2010), pp 3758-3765, ISSN 15280020 20 Myeloid Leukemia – Clinical Diagnosis and Treatment Huntly, B J., Shigematsu, H., Deguchi, K., Lee, B H., Mizuno, S., Duclos, N., Rowan, R., Amaral, S., Curley, D., Williams, I R., Akashi, K & Gilliland, D G (2004)... abl gene and from the Bcr-Abl fused gene Cell, Vol 47, No 2 (October 1986), pp 277-284, ISSN 0092-8674 Tang, R., Faussat, A M., Majdak, P., Marzac, C., Dubrulle, S., Marjanovic, Z., Legrand, O & Marie, J P (2006) Semisynthetic homoharringtonine induces apoptosis via inhibition of protein synthesis and triggers rapid myeloid cell leukemia- 1 down- 24 Myeloid Leukemia – Clinical Diagnosis and Treatment. .. Preudhomme, C., Giles, F., Goldman, J M & Zhou, W (2009) Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation Blood, Vol 114, No 26 (December 2009), pp.5271-5278 ISSN 1528-0020 22 Myeloid Leukemia – Clinical Diagnosis and Treatment O'Hare, T., Shakespeare, W C., Zhu, X., Eide, C A., Rivera, V M., Wang, F., Adrian, L T., Zhou,... syndrome and mesothelioma with promising results (Chaise et al., 2008; Li Z et al., 2005; Oka et al., 2004) 14 Myeloid Leukemia – Clinical Diagnosis and Treatment Another promising target in immunotherapy is PR3, a serine protease which is stored in neutrophils and is over-expressed in 75% of CML patients CD8+ T cells specific for PR3 have been identified in patients in remission following HSCT and correlated... in terms of clinical trial design 3 Combination approaches and investigational compounds The currently available TKIs do not demonstrate efficacy against the T315I mutation suggesting the need for additional strategies such as combination approaches with alternative classes of agents Prior to the introduction of imatinib, interferon (IFN) alpha- 4 Myeloid Leukemia – Clinical Diagnosis and Treatment based... cells in CML patients with an established complete cytogenetic response after 5 years on imatinib 10 Myeloid Leukemia – Clinical Diagnosis and Treatment treatment has been demonstrated (Bhatia et al., 2003) Furthermore, patients with an apparent molecular remission of CML following cessation of imatinib treatment quickly relapse (Cortes et al., 2004) It has been suggested therefore that these quiescent... Van Etten, R A., Donato, N., 16 Myeloid Leukemia – Clinical Diagnosis and Treatment Hunter, A., Dinsdale, D., Tirro, E., Vigneri, P., Nicotera, P., Dyer, M J., Holyoake, T., Salomoni, P & Calabretta, B (2009) Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells Journal of Clinical Investigation, Vol 119,... et al (1993) Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and 18 Myeloid Leukemia – Clinical Diagnosis and Treatment toxicity of a defined T-cell dose Blood, Vol 82, No 8 (October 1993), pp 2310-2318, ISSN 0006-4971 Druker, B J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G M., Fanning,... patients involved, 84 8 Myeloid Leukemia – Clinical Diagnosis and Treatment patients underwent allogeneic HSCT, with a relatively young age of patients reported (median age of 36 years) (Saussele et al., 2010) Chronic phase, frontline therapy Chronic phase, second-line therapy IM-intolerance IM-failure Chronic Phase, third-line therapy In case of dasatinib or nilotinib failure Accelerated and blastic phase... pathway or activation of signalling pathways separate to that of the Bcr-Abl gene and an efflux of IM via multidrug resistant proteins such as p-glycoprotein (Capdeville et al., 2002) The most well-characterised cooperating pathway involves the Src Family Kinases (SFKs) which have 2 Myeloid Leukemia – Clinical Diagnosis and Treatment been demonstrated to play a role in altering responsiveness to TKIs as . MYELOID LEUKEMIA – CLINICAL DIAGNOSIS AND TREATMENT Edited by Steffen Koschmieder and Utz Krug Myeloid Leukemia – Clinical Diagnosis and Treatment Edited. present book focus on clinical aspects of myeloid leukemias and cover the following: Diagnosis and treatment of chronic myeloid leukemia (CML), including standard and high dose imatinib. orders@intechweb.org Myeloid Leukemia – Clinical Diagnosis and Treatment, Edited by Steffen Koschmieder and Utz Krug p. cm. ISBN 978-953-307-886-1 free online editions of InTech Books and Journals