Pulmonary Involvement in Patients with Hematological Malignancies

Élie Azoulay(Editor)

Pulmonary Involvement in Patients with Hematological Malignancies

EditorÉlie Azoulay, M.D., Ph.DService de Réanimation Médicale Hôpital Saint-Louis 1 avenue Claude Vellefaux, 75010, Paris France andMedical Intensive Care Units, Saint-Louis Hospital, Paris 7 University, ParisFranceelie.azoulay@sls.aphp.fr

ISBN 978-3-642-15741-7 e-ISBN 978-3-642-15742-4DOI 10.1007/978-3-642-15742-4Springer Heidelberg Dordrecht London New York

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This book is dedicated to all patients: you are the force that drives our work and our most important teachers. Thank you.

I would like to dedicate this book to all those who are important to me.

vii

Foreword I

In the United States, cancer is the second most common cause of death. Over 560,000 people die of cancer each year. One in four deaths in the United States is due to can-cer. Since the 1970s, the 5-year survival from cancer has increased from 50% to 66%. This improvement in survival reflects earlier diagnosis and more effective therapies and management strategies. As medical technology improves, even more progress is anticipated, but such progress requires experience and analysis, which only highly experienced clinicians and scientists can amass.

Patients with hematologic malignancies are a special challenge to health care pro-viders. In the United States, over 130,000 persons are diagnosed with a hematologic malignancy each year, and over 50,000 individuals die. Half of these hematologic malignancies are acute or chronic leukemias, and the remainder is primarily lympho-mas or multiple myeloma. These hematologic malignancies represent 9.5% of the cancer burden in the United States. These patients undergo a wide variety of immu-nosuppressive therapies that can have impressive results in terms of disease-free sur-vival. However, the toxicities of these regimens can be substantial. Both disease and therapy can cause complications. These complications are very different for different cancers and for different therapies.

Our ability to improve the outcome of hematologic malignancies is due to more precise methods to identify the specific malignant process and to an expanding array of treatments for the underlying malignancies. These treatments are often used in combination regimens over periods of many months to years. These treatments include ionizing radiation, cytotoxic drugs, immunosuppressive agents, and stem cell transplantation. There are now over 50 drugs approved in the United States to treat hematologic malignancies. These drugs have an expanding number of mechanisms of action, ranging from traditional cytotoxic agents to newer drugs that are enzyme inhibitors, monoclonal antibodies, or proteasome inhibitors. Each of these approaches offers promise for specific indications, but also produces enormous complexity in terms of the effects on host immune and inflammatory response, and in terms of the specific organ toxicities they produce.

In this book, Pulmonary Involvement in Patients with Hematological Malignancies, Élie Azoulay has assembled experienced clinicians from around the world to focus on the infectious and non-infectious pulmonary complications that occur in these patients as they are managed with these diverse therapeutic modalities. Dr. Azoulay is renowned for his experience in dealing with such complications and for his careful investigations, which have improved patient care around the world. He has assembled

viii Foreword I

well-published authorities to provide a comprehensive body of information on epide-miology, natural history, diagnosis, and therapy of pulmonary complications.

What makes this book especially useful is the focus on very specific clinical sce-narios. Clinicians who care for patients with hematologic malignancies, which includes most oncologists, infectious disease specialists, and pulmonary-critical care physicians, will immediately be drawn to chapters on long-standing clinical contro-versies such as the role for various types of lung biopsies, new molecular techniques to enhance diagnostic accuracy, and chapters on specific pathogens such as Candida, Aspergillus, and CMV.

Also of special note are chapters that focus on non-infectious challenges such as diffuse alveolar hemorrhage and transfusion-related lung injury. Dr. Azoulay has also included chapters on management problems, such as invasive and non-invasive ven-tilation, transfusion policies, and palliative care, which clinicians will benefit from reviewing in order to be certain they are providing state-of-the-art care.

This book represents the work of experienced, thoughtful, evidence-based clini-cians who provide the authoritative information that only a highly specialized, focused book such as this can supply. Health care providers who deal with this patient popula-tion will find the information and insights in this volume to be extremely valuable and will refer to this book often!

H. Masur

ix

Foreword II

The number of immunocompromised patients has increased over the last decade. Improvements in solid-organ and hematopoietic stem cell transplantation techniques, the expanded use of chemotherapy and steroid use, and the appearance of immuno-modulatory therapies are some of the reasons that explain this increase. The success of the different transplant techniques has generated a great deal of interest in the man-agement of immunocompromised patients among clinicians and basic scientists.

The recognition and management of pulmonary complications that result from immunosuppression are challenging tasks. The lungs may be injured directly through infectious or toxic insults. Conversely, lung disease may result as a secondary event. Pulmonary complications in these patients require a multidisciplinary approach that often involves different specialties. This includes an appreciation of the epidemiol-ogy of post-transplant pulmonary complications, the different diagnoses for these processes, the appropriate diagnostic explorations, and the specific treatments and potential interactions. Some of these patients with pulmonary complications may need intensive care treatment.

The first part of this book is dedicated to non-infectious complications. Dr. Bekele Afessa describes the epidemiology, diagnosis, and treatment of diffuse alveolar hem-orrhage, which is a frequent entity in hematological patients. Dr. Afessa provides a very comprehensive review of non-infectious pulmonary involvement after hematopoi-etic stem cell or bone marrow transplantation. The non-infectious complications comprise a series of entities that may respond to steroid treatment, although in some cases, they will lead to fatal outcomes (graft-versus-host disease).

Pulmonary veno-occlusive disease following hematopoietic stem cell transplanta-tion is a rare complication that is difficult to manage. This subject is reviewed in depth by Drs. Bunte and Burns.

Not infrequently, drugs used to treat cancer patients have cardiovascular compli-cations. One chapter describes how frequently these complications occur, which drugs may be responsible, and how we can decrease the severity of cardiovascular toxicity caused by these drugs.

Diagnosis of pulmonary infiltrates in hematologic malignancies is a difficult prob-lem that often requires bronchoscopic evaluation. Post-mortem studies have helped us to provide the operative values of the techniques that we use in vivo. Dr. Pastores and colleagues have written a comprehensive chapter on this subject.Hematologic malignancies often require transfusions that may be followed by acute lung injury, especially in children. Respiratory infections in patients with hemato-logic malignancies, neutropenia, and bone marrow transplants continue to be a

x Foreword II

serious problem triggered by abnormalities in the function and number of neutro-phils, T and B lymphocytes, anatomic considerations, or a combination of factors. They range from bacterial pneumonias to opportunistic infections. Dr. Soubani et al. provide an update on the etiology, epidemiology, diagnosis, and management of these infections.

In summary, this book edited by Dr. Élie Azoulay gathers a series of excellent chapters written by experts in different problems that cause acute lung injury in hematological patients. The book will be very useful for specialists dealing with these types of problems, and this obviously includes intensive care physicians.

Prof. Antoni Torres

xi

Acknowledgments

I am grateful to all the authors and co-authors who contributed to this book, spending their valuable time to write thoughtful presentations of difficult topics based on their own clinical experience acquired over the years and on a thorough knowledge of the most recent literature. Many thanks to all of you.

I have the deepest respect and consideration for the team working at the medical ICU at the Saint-Louis Hospital. Along with Benoit Schlemmer, I know how lucky we are to work with this group of people who care deeply about their patients and about communicating their skills to their young colleagues. They gladly accept the challenges raised by the sickest patients, while making every effort to avoid non-beneficial care. I learn everyday from them.

I am indebted to the hematologists who work closely with our medical ICU at the Saint Louis Hospital. We learn a lot from each other as we combine our energies to devise the best means of caring for our patients. Our close collaboration has nour-ished important research projects, shedding new light on topics such as the mecha-nisms underlying specific organ dysfunctions, emerging infections, and unexpected drug-related toxicities. This new understanding has helped us to improve patient outcomes.

I am grateful to Dr Francois Vincent for his critical revision of contributions to this book and his willingness to check every single reference. The huge amount of work he put into this book was invaluable.

I owe a debt of gratitude to Meike Stoeck from Springer for her assistance and willingness to adjust to my own pace, as well as to Ute Heilmann for her trust and kindness.

I have a personal thought for Dr Arnaud de Lassence who would certainly have written a contribution for this book. He was among those who knew the most about pulmonary involvement in patients with hematological malignancies. The memory of his bright mind and sparkling enthusiasm continues to nourish my work.

xiii

Part I Preamble and Introduction

1 Managing Patients with Hematological Malignancies for 25 Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Benoit Schlemmer

2 Pulmonary Involvement in Patients with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Élie Azoulay

3 Respiratory Infections in Patients with Hematological Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9Ayman O. Soubani

Part II Epidemiology

4 Epidemiology of Respiratory Events in Patients with HM (Not Including ICU) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41Georg Maschmeyer

5 Epidemiology of Acute Respiratory Failure in Patients with HM (ICU Only) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47Carlos Agustí, Carmen Lucena, and Antoni Torres

6 Noninfectious Lung Involvement in Patients with Hematological Malignancies (Excluding BMT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57Bernard Maitre

7 Noninfectious Pulmonary Involvement in Hematopoietic Stem Cell or Bone Marrow Transplant Recipients . . . . . . . . . . . . . . . . . 63Bekele Afessa

8 Are There Any Pulmonary Issues Specifically Related to Cord Blood Transplants? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83Jonathan Gutman

Contents

xiv Contents

9 Cardiovascular Complications of Cancer Therapeutics . . . . . . . . . . . . 87Aarif Y. Khakoo and Callie S. Kwartler

10 Prophylaxis: Peace of Mind?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117Benoit Guery and Karine Faure

Part III Diagnostic Strategy in HM Patients

11 How Type of Malignancy and Treatment Assist in the Etiological Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123Alexandre Boyer and Didier Gruson

12 Contribution of Radiology in Patients with Hematological Malignancies and Pulmonary Involvement . . . . . . . . . . . . . . . . . . . . . . . 131Claus Peter Heussel

13 Is There Still a Place for Transbronchial Lung Biopsy or Other Lung Biopsy Techniques? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147Christophe Dooms and Vincent Ninane

14 The Increasing Role for Core Needle Biopsy of Pulmonary Lesions in Immunocompromised Patients . . . . . . . . . . . . . . . . . . . . . . . . 155Cédric de Bazelaire, Raphael Calmon, Marion Chapelier, Amélie Pluvinage, and Eric de Kerviler

15 Minimally Invasive Diagnostic Strategy in Immunocompromised Patients with Pulmonary Infiltrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175Laurent Camous, Virginie Lemiale, Achille Kouatchet, David Schnell, Sandra de Miranda, and Élie Azoulay

16 Pleural Effusions and Thoracentesis in Patients with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191Michael G. Alexandrakis, Paschalis Steiropoulos, and Demosthenes Bouros

17 Diagnostic Yield of BAL Fluid Cytology in Hematologic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209Jean-François Bernaudin and Jocelyne Fleury-Feith

18 New Methods for Bacterial Diagnosis in Patients with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223Agnès Ferroni and Jean-Ralph Zahar

19 FDG-PET Imaging in Haematological Patients with Pulmonary Infiltrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235Tomohiko Yamane

Contents xv

20 What Has Been Learned from Postmortem Studies? . . . . . . . . . . . . . . . 243Stephen M. Pastores, Alina O. Dulu, and Shilpa A. DeSouza

Part IV Lung Infections in Patients with HM

21 Common Viral Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257David Schnell, Jérôme Legoff, and Élie Azoulay

22 Emerging Viral Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275Oliver Schildgen

23 Cytomegalovirus Pneumonia in Patients with Hematologic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293Karen J. Vigil and Roy F. Chemaly

24 Herpes Simplex Virus Pneumonia in Patients with Hematologic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301Jharna N. Shah and Roy F. Chemaly

25 Pneumocystis Pneumonia in Non-AIDS Immunocompromised Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313Élie Azoulay, Virginie Lemiale, Achille Kouatchet, François Vincent, Antoine Roux, Guillaume Bollée, and Patricia Roux

26 Diagnosis of Invasive Pulmonary Aspergillosis in Patients with Hematologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327Marie-Elisabeth Bougnoux, Fanny Lanternier, Emilie Catherinot, Felipe Suarez, and Olivier Lortholary

27 Emerging Fungal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337Marcia Garnica and Marcio Nucci

28 Candida Pneumonia in Patients with Hematological Neoplasia . . . . . . 349Carlos Carvajal, Jordi Rello, and Jeffrey Lipman

29 Parasitic Lung Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357Jean-François Timsit, Jean-Paul Brion, and Hervé Pelloux

30 Pulmonary Mycobacterial Infections in Patients with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369Khalid A. Al-Anazi and Asma M. Al-Jasser

Part V Noninfectious Pulmonary Involvement in Patients with HM

31 Pleuropulmonary Changes Induced by Drugs in Patients with Hematologic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387Philippe Camus

xvi Contents

32 Cardiovascular Complications of Cancer and Radiation Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425Callie S. Kwartler and Aarif Y. Khakoo

33 Diffuse Alveolar Hemorrhage in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancy . . . . 437Bekele Afessa

34 Venous Thromboembolism in Patients with Hematologic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449Tarek Sousou and Alok A. Khorana

35 Transfusion-Related Acute Lung Injury in Children with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461Rachel S. Bercovitz, J. Bradley Ball, Marguerite R. Kelher, and Christopher C. Silliman

36 Acute Respiratory Distress Syndrome (ARDS) in Neutropenic Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477Mokart Djamel, Textoris Julien, Ettori Florence, Bruno Chetaille, and Blache Jean-Louis

37 Pulmonary Venoocclusive Disease Following Hematopoietic Stem Cell Transplantation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491Matthew C. Bunte and Linda J. Burns

38 Radiation Pneumonitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499Miguel Gallego Díaz and Jordi Rello Condomines

39 Leukostasis, Infiltration and Pulmonary Lysis Syndrome Are the Three Patterns of Leukemic Pulmonary Infiltrates . . . . . . . . . 509François Vincent

40 Pulmonary MALT Lymphoma: Clinical, Molecular and Therapeutic Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521Marie Wislez, Raphael Borie, Catherine Thieblemont, Marie-France Carette, Martine Antoine, and Jacques Cadranel

41 ARDS During Neutropenia Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . 533Élie Azoulay, Eric Ezingeard, Choupi-Salomon Berckowski, and Michael Darmon

42 Fibrosing Alveolitis in Hematologic Malignancy Patients Undergoing Hematopoietic Cell Transplantation . . . . . . . . . . . . . . . . . . 537Huda Salman, Kenneth R. Cooke, and Hillard M. Lazarus

Contents xvii

Part VI Treatment and Difficult Decisions in Patients with HM and ARF

43 Antibiotic Therapy in Neutropenic Patients . . . . . . . . . . . . . . . . . . . . . . 553Matthieu Legrand, Adeline Max, and Bertrand Gachot

44 Antifungal Therapy in Patients with Hematological Malignancies . . . 569Raoul Herbrecht and Yasmine Nivoix

45 Antiviral Agents in Patients with Hematological Malignancies and Acute Respiratory Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589Michael Sandherr

46 Mechanical Ventilation in Patients with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 597Márcio Soares, Jorge I.F. Salluh, and Pieter O. Depuydt

47 Optimizing Noninvasive Ventilation in Hematological Patients with Acute Respiratory Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607Gilles Hilbert

48 Noninvasive Ventilation to Ensure the Safety of Fiberoptic Bronchoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 617Massimo Antonelli, Giuseppe Bello, and Riccardo Maviglia

49 NIV Outside the ICU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 623Stefano Nava and Sebastiano Mercadante

50 Palliative Noninvasive Mechanical Ventilation in Patients with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 631Anne-Pascale Meert, Thierry Berghmans, and Jean-Paul Sculier

51 Acute Kidney Injury in Cancer Patients . . . . . . . . . . . . . . . . . . . . . . . . . 637Michael Darmon, Laurent Camous, Camille Devanlay, Emmanuel Canet, Benoit Schlemmer, and Fabrice Zeni

52 Septic Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 651David Grimaldi and Frédéric Pène

53 Prognostic Factors for Mortality in the Critically Ill Cancer Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665Kathleen N.S. Cathcart and Jeffrey S. Groeger

54 Managing Critically Ill Cancer Patients: Another Medical Success Story . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671Élie Azoulay, Marcio Soares, Michael Darmon, Dominique Benoit, Stephen Pastores, and Bekele Afessa

xviii Contents

55 Palliative Care and Dyspnea Management in Patients with Hematological Malignancies and Acute Respiratory Failure . . . . 683Amy P. Abernethy, Jane L. Wheeler, and David C. Currow

56 End-of-Life Decisions in Cancer Patients . . . . . . . . . . . . . . . . . . . . . . . . 693Lieve Van den Block, Agnes van der Heide, and Luc Deliens

Part VII Pearls That You Should be Aware Of

57 An Unexpected Diagnosis of Pulmonary Tuberculosis . . . . . . . . . . . . . . 703Virginie Lemiale, A. Seguin, and Élie Azoulay

58 Respiratory Symptoms Occurring 4 Months After Allogeneic Hematopoietic Stem Cell Transplantation. . . . . . . . . . . . . . . . . . . . . . . . 707Anne Bergeron, Séverine Feuillet, Véronique Meignin, Patricia Ribaud, and Abdellatif Tazi

59 Pulmonary Complications of Chronic Lymphocytic Leukemia . . . . . . 715Melhem Solh and Punit Wadhwa

60 Clinical Pearls: Pulmonary Veno-occlusive Disease . . . . . . . . . . . . . . . . 725Jonathan Gutman

61 Cytarabine-Induced Pulmonary Toxicity in Leukemic Patients . . . . . . 729Fabio Forghieri, Leonardo Potenza, Monica Morselli, Monica Maccaferri, Giuseppe Torelli, and Mario Luppi

62 Histoplasmosis in a Patient with Chronic Myelogenous Leukemia. . . . 735Vincent Peigne, Benoît Schlemmer, and Olivier Lortholary

63 Pulmonary Toxicity of Imatinib and Other BCR-ABL Tyrosine Kinase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 741François Vincent

64 Rituximab-Related Pulmonary Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . 751Yair Herishanu, Chava Perry, and Aaron Polliack

65 Cardiogenic Causes of Respiratory Failure in Patients with Hematological Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759Julien Maizel, Berengere Gruson, Jean-Pierre Marolleau, and Michel Slama

66 Pulmonary Alveolar Proteinosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 771François Vincent, H. Tandjaoui, and P.Y. Brillet

Contents xix

67 Pneumocystis jiroveci Pneumonia in a Patient with Diffuse Large B-Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781Hung Chang and Lee-Yung Shih

68 Pulmonary Infiltration in Anaplastic T-Cell Lymphoma . . . . . . . . . . . . 787Christophe Cracco, Julien Mayaux, Sylvain Choquet, Catherine Beigelman, and Frédéric Charlotte

69 A Rapidly Reversible Cause of Pulmonary Embolism . . . . . . . . . . . . . . 793Sophie Georgin-Lavialle, Élie Azoulay, Fabrice Zeni, and Michael Darmon

70 Hairy Cell Leukemia with Pulmonary Infiltrates . . . . . . . . . . . . . . . . . . 797Virginie Lemiale, Véronique Meignin, and Élie Azoulay

71 Trichosporon asahii Infection in a Neutropenic Patient . . . . . . . . . . . . . 801Djamel Mokart, Antoine Sannini, Jean-Paul Brun, Laurent Chow-chine, and Jean-Louis Blache

Part VIII Post Face

72 Who Is This Book for? Reserved to Highly Specialized Teams? . . . . . . 807Laurent Brochard

73 Pulmonary Involvement in Patients with Hematological Malignancies: And Now? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 809Patricia Ribaud and Gérard Socié

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 811