Pulmonary Involvement in Patients with Hematological Malignancies (eBook)

Dr Élie Azoulay is the Assistant Director of the Medical ICU at the Saint-Louis Teaching Hospital, Paris, France. He is a professor of medicine at the Denis Diderot Paris 7 University. From his background as a pulmonologist, Dr Azoulay developed a strong research focus on acute respiratory failure in immunocompromized patients. His PhD work was on respiratory physiology in an experimental model of cancer chemotherapy-related pulmonary toxicity. He has several published clinical research studies on acute respiratory failure in hematology and oncology patients. Also, Dr Azoulay leads a collaborative multicenter group that has performed observational studies, large cohort studies, and randomized controlled trials in cancer patients with ARF. His second major field of interest in clinical research is communication with family members of ICU patients. He constituted a research group in 1997 (the French Famirea Study Group) to evaluate the ability of critical care clinicians to provide effective information to ICU patients and families. Several of his published studies investigated the burden of critical illness in relatives and in ICU clinicians. The group’s major aim is to identify targets for improvement and to test potential interventions in international RCTs in order to advance ICU practices in the field of information and communication. In addition to clinical and research activities, Dr Azoulay teaches pulmonary medicine, critical care medicine, and ethics at the Paris Medical School. He is also associate editor of Intensive Care Medicine, in the editorial board of the American Journal of respiratory and Critical Care medicine, and the chairman of the ethics section of the ESICM. Dr Azoulay is a member of the European board of Pfizer and Gilead.

Copyright Page 5
Dedication 6
Foreword I 8
Foreword II 10
Acknowledgments 12
Contents 14
Part 1: Preamble and Introduction 22
1: Managing Patients with Hematological Malignancies for 25 Years 23
References 24
2: Pulmonary Involvement in Patients with Hematological Malignancies 25
3: Respiratory Infections in Patients with Hematological Malignancies 28
3.1 Introduction 28
3.2 The Immune System Changes in Patients with Hematological Malignancies 29
3.3 Bacterial Pneumonia 32
3.4 Fungal Infections 36
3.4.1 Aspergillus 36
3.4.2 Other Fungi 42
3.5 Cytomegalovirus 44
3.6 Community Respiratory Viruses 46
3.6.1 Respiratory Syncytial Virus (RSV) 47
3.6.2 Parainfluenza Virus 48
3.6.3 Influenza 48
3.6.4 Adenovirus 48
3.6.5 Other Viruses 48
3.7 Conclusion 49
References 49
Part 2: Epidemiology 58
4: Epidemiology of Respiratory Events in Patients with HM (Not Including ICU) 59
References 62
5: Epidemiology of Acute Respiratory Failure in Patients with HM (ICU Only) 64
5.1 Introduction 64
5.2 Main Indications for ICU Admission 65
5.3 Etiology of Pulmonary Infections 65
5.3.1 Bacterial Infections 65
5.3.2 Invasive Fungal Infections 66
5.3.3 Cytomegalovirus (CMV) 66
5.3.4 Respiratory Viruses 66
5.4 Survival in the ICU 67
5.4.1 Selection of Patients 68
5.4.2 Transplant Specific Factors 68
5.4.3 Ventilatory Support 68
5.4.4 Importance of Establishing a Specific Diagnosis 69
5.4.5 Other Factors Influencing Survival 70
5.5 Conclusions 70
References 71
6: Noninfectious Lung Involvement in Patients with Hematological Malignancies (Excluding BMT) 73
6.1 Epidemiology 73
6.2 Venous Thromboembolism in the Hematologic Malignancies 73
6.2.1 Lymphoma 74
6.2.2 Acute Leukemia 74
6.2.3 Multiple Myeloma 74
6.3 Drug-Induced Lung Toxicity 74
6.4 Lung Diseases Induced by Radiation of the Chest 75
6.5 Secondary Lung Cancers 76
6.5.1 Hodgkin’s Lymphoma 76
6.5.2 Second Cancers Following Bone Marrow Transplantation 76
6.6 Other Lung Diseases 77
6.6.1 Pulmonary Extramedullary Hematopoiesis 77
6.6.2 Pulmonary Hypertension and Myelofibrosis 77
6.6.3 Alveolar Proteinosis 77
6.7 Summary 77
References 78
7: Noninfectious Pulmonary Involvement in Hematopoietic Stem Cell or Bone Marrow Transplant Recipients 79
7.1 Introduction 79
7.2 Pulmonary Function Abnormalities 80
7.3 Asthma 82
7.4 Acute Pulmonary Edema 82
7.5 Bronchiolitis Obliterans 82
7.5.1 Incidence and Risk Factors 82
7.5.2 Pathogenesis 83
7.5.3 Clinical Findings and Diagnostic Evaluation 83
7.5.4 Treatment 84
7.5.5 Clinical Course 85
7.6 Bronchiolitis Obliterans Organizing Pneumonia (BOOP) 85
7.6.1 Incidence and Pathogenesis 85
7.6.2 Clinical Presentation and Diagnostic Evaluation 86
7.6.3 Treatment and Prognosis 87
7.7 Idiopathic Pneumonia Syndrome (IPS) 87
7.7.1 Epidemiology 87
7.7.2 Clinical Findings and Diagnostic Evaluation 87
7.7.3 Treatment 87
7.7.4 Clinical Course and Prognosis 88
7.8 Diffuse Alveolar Hemorrhage (DAH) 88
7.9 Periengraftment Respiratory Distress Syndrome (PERDS) 88
7.9.1 Epidemiology 88
7.9.2 Clinical Findings and Diagnostic Evaluation 88
7.9.3 Treatment and Prognosis 88
7.10 Delayed Pulmonary Toxicity Syndrome (DPTS) 88
7.10.1 Clinical Findings and Diagnostic Evaluation 89
7.10.2 Treatment and Prognosis 89
7.11 Pulmonary Cytolytic Thrombi (PCT) 89
7.11.1 Pathogenesis 89
7.11.2 Clinical Findings and Diagnostic Evaluation 89
7.11.3 Treatment and Prognosis 90
7.12 Pulmonary Veno-Occlusive Disease (PVOD) 90
7.12.1 Pathogenesis 90
7.12.2 Clinical Findings and Diagnostic Evaluation 90
7.12.3 Treatment and Prognosis 91
7.13 Other Pulmonary Complications 91
7.13.1 Pulmonary Arterial Hypertension 91
7.13.2 Pulmonary Alveolar Proteinosis 91
7.13.3 Chronic Eosinophilic Pneumonia 92
References 92
8: Are There Any Pulmonary Issues Specifically Related to Cord Blood Transplants? 98
8.1 Introduction 98
8.2 Infusional Toxicities 98
8.3 Preengraftment Syndrome 99
8.4 Infections 99
8.5 Pulmonary Immune Reactions 99
References 99
9: Cardiovascular Complications of Cancer Therapeutics 101
9.1 Introduction 101
9.2 Anthracyclines 104
9.2.1 Genetic Risk 105
9.2.2 Mechanistic Insights 105
9.2.3 Synergistic Interactions 106
9.2.4 Cardioprotective Strategies 107
9.2.5 Conclusions 109
9.3 Mitoxantrone 109
9.3.1 Mechanistic Insights 109
9.4 Tyrosine Kinase Inhibitors 110
9.4.1 Trastuzumab 110
9.4.2 Lapatinib 111
9.4.3 Imatinib 111
9.4.4 Dasatinib and Nilotinib 112
9.4.5 Sunitinib 112
9.4.6 Sorafenib 113
9.4.7 Bevacizumab 113
9.4.8 Conclusions 114
9.5 Monoclonal Antibody Therapies 114
9.5.1 Alemtuzumab 114
9.5.2 Rituximab 114
9.5.3 Cetuximab 115
9.6 5-Fluorouracil and Capecitabine 115
9.7 Cyclophosphamide 115
9.8 Cisplatin and Cisplatin-Based Combination Therapies 116
9.8.1 Toxicity with Combination Therapies 116
9.9 Other Chemotherapeutic Agents 116
9.9.1 Bleomycin 116
9.9.2 Irinotecan 117
9.9.3 Cytarabine 117
9.9.4 Gemcitabine 117
9.10 Microtubule-Altering Therapies 117
9.10.1 Vinca Alkaloids 117
9.10.2 Taxanes 118
9.11 Hormone Therapies 118
9.12 Other Miscellaneous Drugs 118
9.12.1 Bortezomib 118
9.12.2 Thalidomide 119
9.12.3 Interferon-a 119
9.12.4 Arsenic Trioxide 120
9.12.5 IL-2 120
9.13 Cardiotoxicity as a Discovery Platform 120
9.14 Conclusion 121
References 122
10: Prophylaxis: Peace of Mind? 130
References 132
Part 3: Diagnostic Strategy in HM Patients 133
11: How Type of Malignancy and Treatment Assist in the Etiological Diagnosis 134
11.1 Introduction 134
11.2 Risk Factors for Acute Respiratory Failure 135
11.2.1 Neutropenia 135
11.2.2 Deficiencies in Cellular and Humoral Immunity 135
11.2.3 Allogeneic Bone Marrow and Stem Cell Transplantation 135
11.3 Bacterial Pneumonia 136
11.4 Fungal Pneumonia 137
11.5 Viral Pneumonia 137
11.6 Noninfectious Causes of Acute Respiratory Failure 138
11.6.1 Pulmonary Edema 138
11.6.2 Pulmonary Toxicity Syndrome 138
11.6.3 Diffuse Alveolar Hemorrhage 138
11.6.4 Idiopathic Pneumonia Syndrome 138
11.6.5 Graft-Versus-Host Disease 139
11.6.6 Bronchiolitis Obliterans 139
11.6.7 Pulmonary Alveolar Proteinosis 139
11.7 Conclusion 139
References 139
12: Contribution of Radiology in Patients with Hematological Malignancies and Pulmonary Involvement 141
12.1 Early Detection of Pneumonia 141
12.2 Imaging Techniques 142
12.2.1 Chest X-Ray 142
12.2.2 CT 142
12.2.2.1 CT Technique 144
12.2.3 MRI 145
12.2.4 Standard Recommendation 145
12.3 Infectious Pneumonia 145
12.3.1 Identifying Pneumonia 145
12.3.2 Identifying the Cause of Pneumonia 147
12.3.2.1 Bacterial Pneumonia 148
12.3.2.2 Fungal Pneumonia 148
12.3.2.3 Pneumocystis Jiroveci Pneumonia (Pcp) 150
12.3.2.4 Tuberculosis 151
12.3.2.5 Viral Pneumonia 151
12.4 Non-infectious Pulmonary Disease 151
12.4.1 Graft-Versus-Host Disease 152
12.4.2 Radiation Toxicity 152
12.4.3 Drug Toxicity 153
12.4.4 Pulmonary Congestion 154
12.4.5 Leukemic Infiltration 154
12.4.6 Pulmonary Hemorrhage 154
12.5 Extrapulmonary Involvement 154
12.6 Conclusion 154
References 155
13: Is There Still a Place for Transbronchial Lung Biopsy or Other Lung Biopsy Techniques? 157
13.1 Introduction 157
13.2 Is There Still a Place for Transbronchial Lung Biopsy? 158
13.2.1 TBB Increases the Diagnostic Yield of BAL in Non-neutropenic Patients 159
13.2.2 TBB Does Not Increase the Diagnostic Yield of BAL in Patients with Neutropenic Fever or in Patients on Mechanical Ve 159
13.3 Is There Still a Place for CT-Guided Percutaneous Lung Biopsies or Surgical Lung Biopsies? 160
13.3.1 CT-Guided Percutaneous Lung Biopsy 160
13.3.2 Open Lung Biopsy 160
13.3.3 CT-Guided Lung Biopsy Has a High Diagnostic Yield in Patients with Known Hematological Malignancies and Focal Pulmonar 160
13.3.4 The Diagnostic Yield of Surgical Lung Biopsy (SLB) in Patients with Hematological Malignancies and Lung Infiltrates Va 161
13.4 Conclusion 161
References 162
14: The Increasing Role for Core Needle Biopsy of Pulmonary Lesions in Immunocompromised Patients 164
14.1 Introduction 164
14.2 Acronyms 165
14.3 Techniques 165
14.3.1 Preoperative Investigations 165
14.3.1.1 Coagulation Indices 165
14.3.1.2 Pulmonary Function 165
14.3.1.3 Computed Tomography (CT) 166
14.3.2 Biopsy 166
14.3.3 Sample Conditioning 169
14.3.4 Safety, Major and Minor Complications 170
14.3.4.1 Serious Complications 170
Pneumothorax 170
Bleeding 170
Pain 172
14.3.4.2 Minor Complications 172
Monitoring 174
14.4 Efficiency 174
14.4.1 Sensitivity and Adequacy 174
14.4.2 Specific Diagnoses 177
14.5 Conclusion 181
References 181
15: Minimally Invasive Diagnostic Strategy in Immunocompromised Patients with Pulmonary Infiltrates 183
15.1 Introduction 183
15.2 The DIRECT Approach: A Guide for Selecting the Initial Antimicrobial Treatment and Investigations 185
15.3 Bronchoscopy and Bronchoalveolar (FO-BAL) Lavage in Cancer Patients with Pulmonary Infiltrates 186
15.4 Diagnostic Strategy Without Bronchoscopy 186
15.4.1 Laboratory Tests for Diagnosing Infectious 187
15.4.1.1 Bacterial Infections 187
Legionella pneumophila 189
Streptococcus pneumoniae 189
Mycoplasma pneumoniae 190
Chlamydia pneumoniae 190
15.4.1.2 Diagnosis of Viral Respiratory Infections Using Nasopharyngeal Aspirates 190
15.4.1.3 Non-invasive Diagnostic Strategy for Diagnosing Pneumocystis Pneumonia (PCP) 191
15.4.1.4 Diagnosis of Fungal Infection 191
15.4.1.5 Microbial DNA Identification by Blood PCR 192
15.4.1.6 Biomarkers 192
15.5 Conclusion and Avenues for Future Research 193
References 193
16: Pleural Effusions and Thoracentesis in Patients with Hematological Malignancies 198
16.1 Pleural Effusions in NHL 199
16.2 Pleural Effusions in Hodgkin’s Disease 201
16.3 Primary Effusion Lymphoma 201
16.4 Castleman’s Disease 202
16.5 Pyothorax-Associated Lymphoma 202
16.6 Multiple Myeloma 203
16.7 Pleural Effusions in Acute Leukemia 204
16.8 Pleural Effusions in Chronic Lymphocytic Leukemia 204
16.9 Pleural Effusion in Chronic Myelogenous Leukemia (CML) 205
16.10 Pleural Effusions in Myelodysplastic Syndromes 205
16.11 Pleural Effusions in Bone Marrow Transplantation 206
16.12 Pleural Effusions Related to the Treatment of Hematological Malignancies 206
16.13 Thoracentesis 207
References 208
17: Diagnostic Yield of BAL Fluid Cytology in Hematologic Malignancies 216
17.1 Bronchoalveolar Lavage Cytology: Main Technical Points 217
17.1.1 Routine Cytology 217
17.1.2 Electron Microscopy 217
17.1.3 Histochemical and Immunohistochemical Analysis 217
17.1.4 Flow Cytometry 217
17.1.5 Molecular Biology Cell Analysis 218
17.2 Pulmonary Diseases in Which BAL Cytology is Diagnostic 218
17.2.1 BAL Cytology and the Diagnosis of Pulmonary Infectious Disease 218
17.2.2 BAL and Diagnosis of Pulmonary Hemorrhage 220
17.2.3 BAL and Diagnosis of Secondary Alveolar Proteinosis 220
17.2.4 BAL and Diagnosis of Pulmonary Lymphoma 222
17.2.4.1 Primary Pulmonary Lymphoma 222
17.2.4.2 Other Lymphomas and Hodgkin’s Disease 224
17.3 Even When BAL Cytology Is Not Definitely Diagnostic, It Can Provide Valuable Clues 224
17.3.1 Detection of Hematologic Malignant Cells in BAL in Leukemia 224
17.3.2 Other Malignant and Atypical Epithelial Cells in BAL Fluid 225
17.3.3 Drug-Induced Lung Toxicity 225
17.3.4 Miscellaneous Situations 226
17.4 Conclusion 226
References 227
18: New Methods for Bacterial Diagnosis in Patients with Hematological Malignancies 230
18.1 Introduction 230
18.2 PCR 231
18.2.1 Specific PCRs in Respiratory Samples 231
18.2.1.1 Intracellular Bacteria 231
M. pneumoniae, C. pneumoniae 231
Legionella 233
18.2.1.2 Common Bacteria (S. pneumoniae, H. influenzae, Staphylococcus aureus, etc.) 233
18.2.1.3 Mycobacterium tuberculosis and Atypical Mycobacteria 234
18.2.1.4 Multiplex PCR 234
18.2.2 Specific PCR on Blood Samples 234
18.2.3 Universal PCR 235
18.3 Antigen Detection 235
18.3.1 Legionella 235
18.3.2 Streptococcus pneumoniae 236
18.3.2.1 Pneumococcal Antigen Detection in Urine 236
18.3.2.2 Pneumococcal Antigen Detection in Bronchoalveolar Lavage Fluid 237
18.3.2.3 Pneumococcal Antigen Detection in Pleural Fluid 237
18.4 Conclusion 237
References 238
19: FDG-PET Imaging in Haematological Patients with Pulmonary Infiltrates 242
19.1 FDG-PET 242
19.2 Lung Lesions of Haematological Malignancies 243
19.2.1 Malignant Lymphoma 243
19.2.1.1 MALT Lymphoma 243
19.2.1.2 Intravascular Lymphoma 244
19.2.2 Other Haematological Malignancies 244
19.3 Lung Abnormalities Associated with Haematological Disorders 244
19.3.1 Infections Associated with the Immunocompromised State 244
19.3.2 Drug-Induced Pneumonitis 245
19.3.3 Other Drug-Induced Diseases 246
19.3.4 Radiation Pneumonitis 246
19.3.5 Second Malignancies 246
19.4 Conclusion 247
References 247
20: What Has Been Learned from Postmortem Studies? 250
20.1 Introduction 250
20.2 Infectious Findings 251
20.2.1 Invasive Fungal Infections 251
20.2.2 Pneumocystis Jiroveci (Formerly Carinii) Pneumonia 252
20.2.3 Bacterial Infections 252
20.2.4 Viruses 252
20.2.5 Toxoplasmosis 253
20.3 Noninfectious Pulmonary Findings 253
20.3.1 Diffuse Alveolar Damage 253
20.3.2 Diffuse Alveolar Hemorrhage 253
20.3.3 Lymphomatous or Leukemic Infiltration 254
20.3.4 Pulmonary Thromboembolism 254
20.3.5 Bronchiolitis Obliterans with Organizing Pneumonia and Bronchiolitis Obliterans 255
20.3.6 Pulmonary Veno-occlusive Disease 255
20.3.7 Pulmonary Alveolar Proteinosis 256
20.4 Discrepancies Between Clinical and Postmortem Autopsy Findings 256
20.5 Summary 258
References 258
Part 4: Lung Infections in Patients with HM 262
21: Common Viral Pneumonia 263
21.1 Introduction 263
21.2 Common Respiratory Viruses 263
21.3 Epidemiology 264
21.4 Clinical Manifestations 266
21.5 Diagnosis 269
21.5.1 Antiviral Treatment 271
21.6 Prevention 273
21.7 Conclusion 274
References 274
22: Emerging Viral Infections 280
22.1 Introduction 280
22.2 Human Metapneumovirus 280
22.3 Human Bocavirus 281
22.4 Human Coronaviruses 283
22.5 Polyomaviruses 285
22.6 Picornaviruses 286
22.7 Reemerging Viruses 286
22.7.1 Respiratory Syncytial Virus 286
22.7.2 Parainfluenza Viruses 287
22.7.3 Influenza Viruses 287
22.7.4 Adenoviruses 287
References 288
23: Cytomegalovirus Pneumonia in Patients with Hematologic Malignancies 297
23.1 Introduction 297
23.2 Cytomegalovirus Pneumonia 298
23.2.1 Epidemiologic Characteristics 298
23.2.2 Clinical Presentation 298
23.2.3 Diagnosis 298
23.2.3.1 Radiologic Findings 299
23.2.3.2 Lung Biopsy/Cytology 299
23.2.3.3 Microbiology 300
23.2.4 Treatment 300
23.2.4.1 Treatment Options 300
23.2.4.2 Resistance 301
23.2.5 Outcome 301
23.3 Prevention 302
References 302
24: Herpes Simplex Virus Pneumonia in Patients with Hematologic Malignancies 304
24.1 Introduction 304
24.2 Incidence and Transmission 306
24.3 Pathogenesis 306
24.3.1 Pathogenesis in Humans 306
24.3.2 Animal Models 306
24.4 Risk Factors 307
24.5 Clinical Features 307
24.5.1 Clinical Manifestations 307
24.5.2 Coinfections 308
24.5.3 Differential Diagnosis 308
24.6 Diagnosis 308
24.6.1 Virus Isolation 308
24.6.2 Gene Amplification 308
24.6.3 Lung Biopsy/Cytology 309
24.6.4 Radiology 309
24.7 Management 309
24.7.1 Treatment 309
24.7.2 Prophylaxis 309
24.7.3 Resistance to Antivirals 312
24.7.4 Vaccine 312
24.8 Outcome 312
24.9 Prognosis 312
References 313
25: Pneumocystis Pneumonia in Non-AIDS Immunocompromised Patients 315
25.1 Introduction 315
25.2 Transmission 316
25.3 Patients at Risk for PCP 316
25.3.1 Hematological Malignancies 316
25.4 Immunosuppressive Drugs and Risk of PCP 317
25.5 CD4+ Lymphocyte Counts in ­HIV-Negative Patients Developing PCP 317
25.6 Differences in Physiopathology Between Patients with and without AIDS 318
25.7 Clinical and Radiological Presentation of PCP in HIV-Negative Patients 318
25.7.1 Clinical Presentation 318
25.7.2 Radiological Presentation 318
25.8 Diagnostic Strategy 318
25.8.1 Respiratory Samples Collecting Techniques 318
25.8.2 Laboratory Diagnosis 320
25.8.2.1 Direct Examination 321
25.8.2.2 Polymerase Chain Reaction as a Significant Advance for Diagnosing PCP 321
25.8.2.3 PCR and Colonization 322
25.8.2.4 Real-Time Quantitative PCR 323
25.8.2.5 S-Adenosylmethionine Plasmatic Concentration Dosage 323
25.8.2.6 (1–3)-b-d-Glucan 323
25.9 Prognosis of PCP in HIV-Negative Patients 323
25.9.1 Mortality 323
25.9.2 Prognostic Factors 324
25.10 Curative Treatment of PCP 324
25.10.1 Antimicrobial Therapy 324
25.10.2 Adjuvant Steroids 324
25.11 Prophylaxis of Pneumocystis pneumonia 325
25.11.1 Antimicrobial Drugs Available 325
25.11.2 Indications for Prophylaxis 325
25.12 Conclusion 325
References 325
26: Diagnosis of Invasive Pulmonary Aspergillosis in Patients with Hematologic Diseases 328
26.1 Risk Factors for Invasive Aspergillosis in Hematology Patients 328
26.2 Clinical Features 329
26.3 Chest Computed Tomography Scan 329
26.4 Laboratory Diagnosis 330
26.4.1 Mycological Microscopy and Culture 330
26.4.1.1 Direct Microscopy 330
26.4.1.2 Fungal Culture 331
26.4.1.3 Identification of Aspergillus spp. 331
26.4.1.4 Antifungal Susceptibility Testing 331
26.4.2 Histopathology 331
26.4.3 Detection of Circulating Surrogate Markers 331
26.4.3.1 Detection of Galactomannan Antigen 332
Serum Aspergillus GM Detection 332
Major Causes of Variable Test Performances 332
High Variations of GM Levels in Serum Conditions 332
False-Positive Detection 332
GM as a Marker of Aspergillosis Outcome 332
BAL Aspergillus GM Detection 332
26.4.3.2 Detection of Beta-1-3-D-Glucan Antigen 333
26.4.3.3 DNA Detection by PCR 333
References 334
27: Emerging Fungal Infections 338
27.1 Introduction 338
27.2 The Host 339
27.3 The Fungi 340
27.4 Clinical Manifestation 340
27.5 Radiology 342
27.6 Other Diagnostic Tools 344
27.7 Treatment 345
27.8 Conclusions 346
References 346
28: Candida Pneumonia in Patients with Hematological Neoplasia 350
28.1 Introduction 350
28.2 Epidemiology 351
28.3 Risk Factors for Invasive Pulmonary Candidiasis 351
28.4 Diagnosis 352
28.5 Treatment 353
28.6 Conclusion 356
References 356
29: Parasitic Lung Infections 358
29.1 Host–Parasite Interaction 358
29.1.1 Toxoplasmosis 359
29.1.2 Strongyloidiasis 360
29.2 Toxoplasmosis 360
29.2.1 Clinical Presentation 361
29.3 Strongyloidiasis 362
29.3.1 Clinical Presentation 362
29.4 Treatment of Strongyloidiasis and Toxoplasmosis 363
29.5 Toxoplasmosis 363
29.5.1 Possible Alternative Regimens 363
29.5.2 Management of Pulmonary Toxoplasmosis in Hematopoietic Stem Cell Transplant Recipients 364
29.5.3 Primary Prophylaxis 364
29.6 Strongyloidiasis 364
29.6.1 Management of Hyperinfection or Disseminated Infection 365
29.6.2 Preventive Therapy 365
29.6.3 Preventing Disease and Disease Recurrence 365
29.6.4 Clinical Vignette 366
29.6.4.1 Disseminated Toxoplasmosis 366
References 367
30: Pulmonary Mycobacterial Infections in Patients with Hematological Malignancies 369
30.1 Introduction 369
30.2 Incidence and Risk Factors of Tuberculosis in Patients with Hematological Malignancies 369
30.3 Clinical Presentations of Tuberculosis in Patients with Hematological Malignancies 370
30.4 Diagnosis of Active Tuberculosis 371
30.4.1 Clinical Manifestations 371
30.4.1.1 First-Line Investigations 371
30.4.1.2 Other Investigations 371
30.4.1.3 New Tests for Tuberculosis 373
30.4.1.4 Therapeutic Trial 374
30.5 Outcomes and Treatment of Tuberculosis in Patients with Hematological Malignancies 374
30.5.1 Antituberculous Drug Therapy 374
30.5.1.1 Antituberculous Drugs 374
30.5.1.2 Compliance and Tolerance 375
30.5.1.3 Side Effects 375
30.5.1.4 Corticosteroid Therapy 375
30.5.1.5 Surgery 376
30.6 Multidrug Resistant Tuberculosis 376
30.7 Latent Tuberculosis 376
30.7.1 Diagnosis of Latent Tuberculosis 376
30.7.1.1 Tuberculosis Chemoprophylaxis in Patients with Hematological Malignancies 376
30.8 Nontuberculous Mycobacterial Infections 377
30.8.1 Diagnosis of NTM Nontuberculous Mycobacterial Infections 377
30.8.1.1 Treatment of Nontuberculous Mycobacterial Infections 377
30.9 Mycobacterial Infections in Stem-Cell Transplant Recipients 378
References 379
Part 5: Noninfectious Pulmonary Involvement in Patients with HM 384
31: Pleuropulmonary Changes Induced by Drugs in Patients with Hematologic Diseases 385
31.1 Introduction 385
31.2 Diagnostic Criteria for Drug-Induced Respiratory Disease 387
31.3 Patterns of Reactions to Drugs and Radiation 388
31.3.1 Interstitial-Infiltrative Lung Diseases (ILD) 388
31.3.1.1 Cellular or Nonspecific Interstitial Pneumonia 389
31.3.1.2 Eosinophilic Pneumonia 389
31.3.1.3 Interstitial Lung Disease with a Granulomatous Component 390
31.3.1.4 Organizing Pneumonia 390
31.3.1.5 Diffuse Alveolar Damage and the Chemotherapy Lung 390
31.3.1.6 Cell Lysis Pneumopathy 393
31.3.1.7 Drug-Induced and Iatrogenic Pulmonary Fibrosis 393
31.3.1.8 Drug-Induced Pulmonary Edema 393
31.3.1.9 Diffuse Alveolar Hemorrhage 394
31.3.2 Pulmonary Nodules 394
31.3.3 Acute Chest Pain 394
31.3.4 Bronchospasm 394
31.3.5 Pleural Involvement 395
31.3.6 Late Changes 395
31.3.7 Drug-Induced Lymphoma and Second Cancers 395
31.4 Drugs Causing Pleuropulmonary Toxicity in Hematology 396
31.4.1 Amphotericin B 396
31.4.2 Anti-thymocyte Globulin 396
31.4.3 All-trans-Retinoic Acid (ATRA) and Arsenic Trioxide As2O3 396
31.4.4 Azacytidine 397
31.4.5 Bis-Chlororethyl Nitrosourea Carmustine 397
31.4.6 Bleomycin 397
31.4.7 Blood and Blood Products: Transfusion-Related Acute Lung Injury 399
31.4.8 Bortezomib 401
31.4.9 Busulfan (Myleran) 401
31.4.10 Chlorambucil 401
31.4.11 Colony-Stimulating Factors 401
31.4.12 Corticosteroids 402
31.4.13 Cyclophosphamide 402
31.4.14 Cytosine-Arabinoside (Ara-C) 402
31.4.15 Dasatinib 403
31.4.16 Deferoxamine 403
31.4.17 Etoposide 403
31.4.18 Fludarabine 403
31.4.19 Gemcitabine 404
31.4.20 Hydroxyurea 404
31.4.21 Interferon 404
31.4.22 Imatinib 405
31.4.23 Lenalidomide 405
31.4.24 Melphalan 405
31.4.25 Methotrexate 406
31.4.26 Procarbazine 407
31.4.27 Rituximab 407
31.4.28 Thalidomide 408
31.4.29 Vinca Alkaloids 408
31.5 Adverse Effects of Radiation Therapy to the Chest 408
References 409
32: Cardiovascular Complications of Cancer and Radiation Therapy 422
32.1 Introduction 422
32.2 Cardiovascular Complications of Cancer 423
32.2.1 Primary Cardiac Tumors 423
32.2.2 Venous Thromboembolism 424
32.2.3 Pericardial Disease 425
32.3 Radiation Therapy-Induced Cardiovascular Disease 426
32.3.1 Pericardial Disease 426
32.3.2 Valvular Disease 426
32.3.3 Accelerated Coronary Artery Disease 427
32.3.4 Cardiomyopathy 427
32.3.5 Peripheral Vessel Stenosis 428
32.3.6 Cardiac Baroreceptor Dysfunction 428
32.3.7 Conclusion 429
32.4 Conclusion 429
References 429
33: Diffuse Alveolar Hemorrhage in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancy 433
33.1 Introduction 433
33.2 Diagnostic Criteria 433
33.3 DAH in Patients with Hematologic Malignancy 434
33.4 DAH in BMT Recipients 435
33.4.1 Incidence 435
33.4.2 Risk Factors 435
33.4.3 Pathogenesis 436
33.4.3.1 Lung Injury 436
33.4.3.2 Inflammation 437
33.4.3.3 Cytokine Release 437
33.4.4 Clinical Findings and Course 437
33.4.5 Laboratory and Radiographic Findings 438
33.4.6 Differential Diagnosis 439
33.4.7 Treatment 439
33.4.8 Prognosis 440
References 440
34: Venous Thromboembolism in Patients with Hematologic Malignancies 444
34.1 Introduction 444
34.2 Risk Factors for VTE in Hematologic Malignancies 445
34.2.1 Type of Malignancy 445
34.2.2 Therapeutic Agents 445
34.2.3 Initial Period After Diagnosis 446
34.2.4 Stem Cell Transplantation 446
34.2.5 Comorbid Conditions 446
34.3 Candidate Biomarkers of VTE 446
34.4 A Predictive Risk Assessment Score 447
34.5 VTE Thromboprophylaxis in Hematologic Malignancy 447
34.5.1 Hematologic Cancer Inpatients 448
34.5.2 Hematologic Cancer Outpatients 449
34.5.3 Central Venous Catheter Thromboprophylaxis 450
34.6 Treatment of VTE in Cancer Patients 450
34.6.1 Initial Anticoagulation 450
34.6.2 Long-Term Anticoagulation 450
34.6.3 Use of Vena Caval Filters 451
34.7 Summary and Future Directions 451
References 451
35: Transfusion-Related Acute Lung Injury in Children with Hematological Malignancies 455
35.1 Introduction 455
35.2 Transfusion-Related Acute Lung Injury 457
35.2.1 Diagnosis and Treatment 457
35.2.2 Epidemiology 458
35.2.3 The Role of the Neutrophil 459
35.3 Etiology of TRALI: Antibody- and Nonantibody-Mediated TRALI 461
35.3.1 The Role of Human Leukocyte Antigen, Major Histocompat­ibility Complex Class I Antibodies 461
35.3.2 The Role of HLA MHC Class II Antibodies 462
35.3.3 Laboratory Investigation of HLA Antibodies 463
35.3.4 Nonantibody TRALI: The Role of Biologic Response Modifiers 464
35.4 Treatment-Related Risk Factors for ALI in Patients with Hematologic Malignancies 465
35.5 TRALI Mitigation 465
35.6 Concluding Remarks 465
References 465
36: Acute Respiratory Distress Syndrome (ARDS) in Neutropenic Patients 470
36.1 Introduction 470
36.2 Epidemiology 471
36.3 Pathophysiology 472
36.3.1 Histological Features 473
36.3.2 Bronchoalveolar Lavage Fluid 473
36.3.3 Neutropenia and Sequestered Neutrophils 474
36.3.4 Alveolar Macrophages and Circulating Monocytes 475
36.3.5 Possible Role for Platelets 475
36.3.6 Other Mechanisms and Other Mediators 476
36.4 Different Pathophysiological Pathways for Neutropenic and Non-neutropenic ARDS Patients: Clinical Implications 476
36.5 Therapeutic Management 477
36.5.1 Empirical Antimicrobial Therapy 477
36.5.2 Directed Antimicrobial Therapy 479
36.6 Prognosis and Prognostic Factors 479
36.7 Conclusion 480
References 480
37: Pulmonary Venoocclusive Disease Following Hematopoietic Stem Cell Transplantation 484
37.1 Epidemiology 484
37.2 Pathophysiology 487
37.3 Clinical Manifestations and Diagnosis 488
37.4 Treatment 489
37.5 Complications and Prognosis 490
37.6 Conclusion 490
References 490
38: Radiation Pneumonitis 492
38.1 Introduction 492
38.2 Incidence 493
38.3 Risk Factors 493
38.4 Pathobiology 494
38.5 Diagnosis 495
38.5.1 Clinical Manifestations 495
38.5.2 Radiology 495
38.5.3 Lung Functional Test 497
38.6 Treatment 497
38.7 Prevention 497
38.7.1 Radiation Techniques 497
38.7.2 Drugs 498
38.8 Conclusions 498
References 498
39: Leukostasis, Infiltration and Pulmonary Lysis Syndrome Are the Three Patterns of Leukemic Pulmonary Infiltrates 501
39.1 Introduction 501
39.2 Pulmonary Leukostasis 501
39.3 Pulmonary Leukemic Infiltration 503
39.4 Acute Lysis Pneumopathy 506
39.5 Management 507
References 509
40: Pulmonary MALT Lymphoma: Clinical, Molecular and Therapeutic Aspects 513
40.1 Terminology 513
40.2 MALT Lymphoma 514
40.2.1 Marginal Zone and Bronchial Mucosa-Associated Lymphoid Tissue 514
40.2.2 Molecular Basis 515
40.2.3 Epidemiology 515
40.3 Clinical and Radiological Signs of Pulmonary MALT Lymphoma 515
40.4 Diagnostic Approach 516
40.4.1 Contribution of Bronchoscopy 517
40.4.2 Contribution of Other Diagnostic Alternatives 517
40.4.3 Diagnostic Criteria 517
40.4.3.1 Results of Conventional Histology Analysis 517
40.4.3.2 Contribution of Immunohistochemistry 517
40.4.3.3 Contribution of Molecular Biology 518
40.5 Differential Diagnosis: Clinical and Pathological 518
40.6 Pretreatment Staging 519
40.7 Progression, Prognosis, and Treatment 520
40.7.1 Progression and Prognostic Factors 520
40.7.2 Principles Underlying Treatment 520
40.8 Conclusion 521
References 521
41: ARDS During Neutropenia Recovery 524
41.1 Introduction 524
41.2 Clinical Presentation and Risk Factors 524
41.3 Evidence Supporting a Risk of Respiratory Failure During Neutropenia Recovery 525
41.4 Pathophysiology 526
41.5 Conclusions 526
References 526
42: Fibrosing Alveolitis in Hematologic Malignancy Patients Undergoing Hematopoietic Cell Transplantation 528
42.1 Introduction 529
42.2 Fibrosing Alveolitis Secondary to Pulmonary Infections 529
42.3 Fibrosing Alveolitis Secondary to Noninfectious Etiologies 531
42.3.1 Radiation Therapy 531
42.3.2 Chemotherapy 532
42.3.3 Chronic Pulmonary Dysfunction After Hematopoietic Cell Transplantation 534
42.4 Conclusion 537
References 538
Part 6: Treatment and Difficult Decisions in Patients with HM and ARF 542
43: Antibiotic Therapy in Neutropenic Patients 543
43.1 Introduction 543
43.2 Bacterial Epidemiology in Neutropenic Patients 544
43.3 Strategies for Empirical Antibiotic Therapy 544
43.3.1 Principles Underlying First-Line Antibiotic Therapy 544
43.3.2 Choice of the First-Line Antibiotic Regimen 547
43.3.2.1 Site of Care and Route of Empirical Antibiotic Therapy 547
43.3.2.2 Antibiotic Combinations 548
43.3.3 Adapting the Antibiotics: Treatment Duration 550
43.4 Pharmacodynamic and Pharmacokinetic Considerations 553
43.5 Prophylactic Antibiotics 553
43.6 Conclusion 553
References 554
44: Antifungal Therapy in Patients with Hematological Malignancies 558
44.1 Introduction 558
44.2 Polyenes 558
44.2.1 Amphotericin B Deoxycholate 559
44.2.1.1 Pharmacokinetics 559
44.2.1.2 Clinical Efficacy 560
44.2.1.3 Tolerability 561
44.2.2 Amphotericin B Colloidal Dispersion 561
44.2.2.1 Pharmacokinetics 561
44.2.2.2 Clinical Efficacy 561
44.2.2.3 Tolerability 561
44.2.3 Amphotericin B Lipid Complex 561
44.2.3.1 Pharmacokinetics 561
44.2.3.2 Clinical Efficacy 561
44.2.3.3 Tolerability 562
44.2.4 Liposomal Amphotericin B 562
44.2.4.1 Pharmacokinetics 562
44.2.4.2 Clinical Efficacy 562
44.2.4.3 Tolerability 562
44.3 Azoles 562
44.3.1 Fluconazole 563
44.3.1.1 Pharmacokinetics 563
44.3.1.2 Clinical Efficacy 563
44.3.1.3 Tolerability 564
44.3.2 Itraconazole 564
44.3.2.1 Pharmacokinetics 564
44.3.2.2 Clinical Efficacy 564
44.3.2.3 Tolerability 565
44.3.3 Voriconazole 565
44.3.3.1 Pharmacokinetics 565
44.3.3.2 Clinical Efficacy 566
44.3.3.3 Tolerability 566
44.3.4 Posaconazole 567
44.3.4.1 Pharmacokinetics 567
44.3.4.2 Clinical Efficacy 568
44.3.4.3 Tolerability 568
44.3.5 Isavuconazole 569
44.4 Echinocandins 569
44.4.1 Caspofungin 569
44.4.1.1 Pharmacokinetics 569
44.4.1.2 Clinical Efficacy 570
44.4.1.3 Tolerability 570
44.4.2 Micafungin 570
44.4.2.1 Pharmacokinetics 570
44.4.2.2 Clinical Efficacy 570
44.4.2.3 Tolerability 570
44.4.3 Anidulafungin 571
44.4.3.1 Pharmacokinetics 571
44.4.3.2 Clinical Efficacy 571
44.4.3.3 Tolerability 571
44.5 Flucytosine 571
44.6 Combination Antifungal Therapy 571
References 572
45: Antiviral Agents in Patients with Hematological Malignancies and Acute Respiratory Failure 578
45.1 Introduction 578
45.2 Herpes Viruses 578
45.2.1 Acyclovir and Valacyclovir 578
45.2.2 Ganciclovir and Valganciclovir 580
45.2.3 Foscarnet 581
45.2.4 Cidofovir 581
45.2.5 Maribavir 582
45.3 Respiratory Viruses 582
45.3.1 Neuraminidase Inhibitors 582
45.3.1.1 Oseltamivir 582
45.3.1.2 Zanamivir 583
45.3.2 Amantadine and Rimantadine 583
45.3.3 Ribavirin 583
45.3.4 Palivizumab 584
References 584
46: Mechanical Ventilation in Patients with Hematological Malignancies 585
46.1 Epidemiology 586
46.2 Outcome Evaluation and Prognostic Factors 586
46.2.1 Short- and Long-Term Outcomes 586
46.2.1.1 Specific Diagnoses and Characteristics Related to the Malignancy 586
46.2.1.2 Main Prognostic Factors 589
46.3 When to Reach for the Tube Instead of the Mask 589
References 592
47: Optimizing Noninvasive Ventilation in Hematological Patients with Acute Respiratory Failure 595
47.1 Introduction/Rationale for Optimizing Noninvasive ventilation 595
47.2 Optimizing Noninvasive Ventilation 597
47.2.1 Taking into Consideration the Mechanisms of Improvement with NIV 597
47.2.2 Optimizing the Selection of Patients 598
47.2.3 Optimizing Equipment and Techniques 598
47.2.3.1 Interface 598
47.2.3.2 Ventilators and Ventilatory Modes 600
47.2.3.3 Chosing a Continuous or Discontinuous Approach 601
47.2.3.4 Predictive Factors of NIV Outcome 602
47.3 Conclusions 602
References 603
48: Noninvasive Ventilation to Ensure the Safety of Fiberoptic Bronchoscopy 605
48.1 Introduction 605
48.2 Rationale for Using NIV During FB 606
48.3 Review of the Literature 607
48.4 Contraindications 607
48.5 Practical Considerations 607
48.6 Conclusion 609
References 610
49: NIV Outside the ICU 611
49.1 Introduction 611
49.2 When to Start NIV Outside the ICU 612
49.3 The Rationale for Using NIV in Hematological Patients with Acute Respiratory Failure 613
49.4 Clinical Use of NIV to Treat Acute Respiratory Failure 614
49.5 Conclusions 616
References 616
50: Palliative Noninvasive Mechanical Ventilation in Patients with Hematological Malignancies 618
References 621
51: Acute Kidney Injury in Cancer Patients 623
51.1 Introduction 623
51.2 Consequences of Acute Renal Failure 624
51.2.1 Prognostic Impact of AKI 624
51.2.2 Kidney Lung Crosstalk 624
51.2.2.1 Kidney–Lung Interaction 624
51.2.2.2 Lung–Kidney Interaction 625
51.2.3 AKI in Patients with ALI/ARDS and in Critically Ill Cancer Patients 625
51.3 Specific Causes of Acute Renal Failure in Onco-hematological Patient 626
51.3.1 Acute Tumor Lysis Syndrome 626
51.3.1.1 Definition and Risk Factors 626
51.3.1.2 Treatment 626
Fluid Expansion 627
Urine Alkalinization 627
Hypouricemic Agents 627
Prevention of Nephrocalcinosis 628
Indication and Timing of Renal Replacement Therapy 628
Management of Cancer Chemotherapy in Patients with Tumor Lysis Syndrome 628
51.3.2 AKI and Myeloma 628
51.3.2.1 Epidemiology 628
51.3.2.2 Prevention and Treatment 629
51.3.3 Methotrexate Intoxication 630
51.3.3.1 Toxicity of Methotrexate 630
51.3.3.2 Prevention Measures 630
51.3.3.3 Treatment of Methotrexate Intoxication 630
51.3.4 Veno-occlusive Disease/Sinusoidal Obstruction Syndrome 630
51.3.5 Thrombotic Microangiopathy 631
51.4 Conclusion 632
References 632
52: Septic Shock 637
52.1 Introduction 637
52.2 Epidemiology of Septic Shock in Patients with Malignancies 637
52.2.1 Incidence 637
52.2.2 Site of Infection and Type of Pathogens 638
52.2.2.1 Infections in Patients with Hematological Malignancies 638
52.2.2.2 Particularities of Septic Shock in Cancer Patients 639
52.2.3 Risk Factors of Septic Shock in Patients with Hematological Malignancies 639
52.2.3.1 Acquired Immune Disorders 639
52.2.3.2 Genetic Predisposition 639
52.3 Outcomes of Septic Shock in Patients with Malignancies 640
52.4 Prognostic Factors of Septic Shock: The Critical Role of Organ Failures 641
52.5 Intended Management of Septic Shock in Patients with Hematological Malignancies 642
52.5.1 Antimicrobial Treatment and Source of Infection Control 642
52.5.2 Hemodynamic Support 643
52.5.3 Ventilatory Support 643
52.5.4 Renal Replacement Therapy 643
52.5.5 Steroid Supplementation 644
52.5.6 Blood Glucose Control 644
52.5.7 Recombinant Activated Protein C 644
52.5.8 Blood Product Administration 645
52.5.9 Immune Defense Restoration 645
52.6 Conclusion 646
References 646
53: Prognostic Factors for Mortality in the Critically Ill Cancer Patient 650
53.1 Introduction 650
53.2 Reasons for ICU Admission 651
53.3 Withholding Admission 652
53.4 Predictors of Outcomes 652
53.5 The ICU Trial 652
53.6 Conclusion 653
References 653
54: Managing Critically Ill Cancer Patients: Another Medical Success Story 656
54.1 Introduction 656
54.2 Prognosis of Cancer Patients Requiring ICU Support: The Ten Truths 657
54.2.1 Short-Term Survival After a Critical Care Illness Has Improved 657
54.2.2 Classic Predictors of Mortality Are No Longer Relevant 657
54.2.3 Improved Understanding of Organ Dysfunction 658
54.2.4 Some Groups of Patients Have High and Unchanged Mortality 658
54.2.5 Triage Criteria That Are Usually Used Are Ineffective 659
54.2.6 At Least 3 Days of ICU Management Before Making End-of-Life Decisions (ICU Trial) 659
54.2.7 Finding a Balance Between Non-invasive Treatments and Avoiding Delays in Optimal Therapies 660
54.2.8 Close Relationship and Collaboration Need to Be Developed Between Hematologists and Oncologists to Increase the Skill 660
54.2.9 Early Admission to the ICU for Cancer Patients 660
54.2.10 Doing Everything That Can Be Done, Including Cancer Chemotherapy 660
54.3 Broadening ICU Admission Policies and Clarifying the Patient’s Code Status at the Time of Admission 660
54.4 Unanswered Questions and Research Agenda 663
54.5 Conclusions 664
References 664
55: Palliative Care and Dyspnea Management in Patients with Hematological Malignancies and Acute Respiratory Failure 668
55.1 Introduction 668
55.2 Dyspnea 669
55.2.1 Assessment 669
55.2.2 Mechanisms 669
55.3 Palliative Care for Intractable Dyspnea 669
55.4 Pharmacological Interventions 669
55.4.1 Oral and Parenteral Opioids 670
55.4.2 Psychotropic Drugs 670
55.4.2.1 Benzodiazepines 671
55.4.2.2 Other Anxiolytics 671
55.4.2.3 Selective Serotonin Reuptake Inhibitors (SSRIs) 671
55.4.2.4 Inhaled Frusemide 671
55.4.2.5 Heliox28 672
55.5 Oxygen Therapy 672
55.6 Non-pharmacological Interventions 673
55.6.1 Psychosocial Support 673
55.6.1.1 Breathing Techniques 673
55.7 Conclusions 674
References 674
56: End-of-Life Decisions in Cancer Patients 677
56.1 Introduction 677
56.2 Conceptual Framework of End-of-Life Decisions 678
Box 56.1 Conceptual framework for medical end-of-life decisions with a possible or certain life-shortening effect [3, 4, 679
56.3 Methodology of the European Study on End-of-Life Decisions (EURELD) Study 2001 679
56.3.1 Questionnaire 679
56.4 Epidemiology of End-of-Life Decisions Among Cancer Patients: European Study on End-of-Life Decisions (EURELD) 2001 680
56.5 A Comparison of End-of-Life Decisions Between Cancer and Non-cancer Patients in Belgium 681
56.6 Conclusion 683
References 683
Part 7: Pearls That You Should be Aware Of 685
57: An Unexpected Diagnosis of Pulmonary Tuberculosis 686
57.1 Case Report 686
57.2 Diagnoses Suspected at ICU Admission 687
57.2.1 Lung Infection 687
57.2.2 Noninfectious Diseases 687
57.3 Outcome 688
57.4 Discussion 688
References 689
58: Respiratory Symptoms Occurring 4 Months After Allogeneic Hematopoietic Stem Cell Transplantation 690
58.1 Case Study 690
58.2 Discussion 693
58.2.1 Was Our Patient’s Clinical Picture Typical of Cases of Bronchiolitis Obliterans Complicating Allogeneic Hematopoietic 693
58.2.2 Was Pulmonary Function Testing Consistent with the Diagnosis of BO? 694
58.2.3 Was the Lung Computed Tomography Scan Informative for Diagnosing BO? 694
58.2.4 What About the Cell Profile of Bronchoalveolar Lavage for Our patient? 695
58.2.5 Was the Lung Biopsy Necessary for Our Patient? 695
58.2.6 What A Posteriori Analysis Can Be Made for the Therapeutic Management of Our patient? 696
58.3 Conclusion 696
References 696
59: Pulmonary Complications of Chronic Lymphocytic Leukemia 698
59.1 Introduction 698
59.2 Pulmonary Complications of CLL 699
59.3 Infectious Pulmonary Complications 699
59.4 Noninfectious Lung Complications 701
59.4.1 Pulmonary Leukostasis 701
59.4.2 Pleural Effusion 701
59.4.3 Leukemic Infiltrates 702
59.4.4 Airway Obstruction 702
59.4.5 Constrictive Bronchiolitis 702
59.4.6 Drug-Related Pulmonary Toxicity 702
59.4.7 CLL and Lung Cancer 703
59.5 Conclusions 704
References 704
60: Clinical Pearls: Pulmonary Veno-occlusive Disease 707
References 709
61: Cytarabine-Induced Pulmonary Toxicity in Leukemic Patients 710
References 714
62: Histoplasmosis in a Patient with Chronic Myelogenous Leukemia 716
62.1 Case Presentation 716
62.2 Comment 717
References 720
63: Pulmonary Toxicity of Imatinib and Other BCR-ABL Tyrosine Kinase Inhibitors 721
63.1 Case Report 721
63.2 Incidence of Lung Manifestations During the Course of Treatment with Imatinib 723
63.3 Clinical and Radiological Findings 723
63.4 Histopathological Findings 723
63.5 Management 724
63.6 Pulmonary Manifestations Associated with the Other BCR-ABL Tyrosine Kinase Inhibitors 724
63.7 Conclusion 725
References 728
64: Rituximab-Related Pulmonary Toxicity 730
64.1 The Case 730
64.1.1 Rituximab-Related Pulmonary Toxicity 732
64.1.2 Acute Pulmonary Reactions 732
64.1.3 Subacute Pulmonary Reactions 732
64.1.4 Mechanism of Toxicity 733
64.1.5 Differential Diagnosis 733
64.1.6 Clinical Investigations 734
64.1.7 Clinical Course and Treatment 734
References 735
65: Cardiogenic Causes of Respiratory Failure in Patients with Hematological Malignancies 737
65.1 Case Report 737
65.2 Introduction 738
65.3 Acute Heart Failure 738
65.3.1 Acute Coronary Syndromes 738
65.3.2 Arrhythmias 739
65.3.3 Fluid Overload 740
65.4 Chronic Heart Failure 740
65.4.1 Chemotherapy-Related Cardiotoxicity 740
65.4.2 Radiation 741
65.4.3 Cardiac Manifestations of Amyloidosis 741
65.5 Other Causes of Cardiogenic Acute Respiratory Failure 742
65.5.1 Tamponade 742
65.5.2 Pulmonary Embolism 742
65.6 Clinical, Laboratory, and Imaging Findings 742
65.6.1 Clinical, Laboratory, and X-Ray Findings 743
65.6.2 Echocardiography 743
65.7 Conclusion 745
References 747
66: Pulmonary Alveolar Proteinosis 749
66.1 Introduction 749
66.2 Case Report 749
66.3 Clinical Presentation of PAP 751
66.4 Radiological Features 752
66.5 Pulmonary Function 753
66.6 Diagnosis 754
66.7 Complications 754
66.8 Treatment 754
66.9 Idiopathic PAP and GM-CSF 755
66.10 PAP and Hematological Malignancies 755
66.11 Conclusion 756
References 756
67: Pneumocystis jiroveci Pneumonia in a Patient with Diffuse Large B-Cell Lymphoma 759
67.1 Case Presentation 759
67.2 Discussion 760
References 762
68: Pulmonary Infiltration in Anaplastic T-Cell Lymphoma 764
68.1 Background 764
68.2 Case Description 765
68.3 Discussion 767
References 767
69: A Rapidly Reversible Cause of Pulmonary Embolism 769
69.1 Introduction 769
69.2 Case Report 769
69.3 Discussion 770
69.4 Conclusion 771
References 772
70: Hairy Cell Leukemia with Pulmonary Infiltrates 773
70.1 Case Report 773
70.2 Suspected Diagnoses 774
70.3 Results of Investigations and Outcome 775
70.4 Discussion 776
References 776
71: Trichosporon asahii Infection in a Neutropenic Patient 777
71.1 Case Report 777
71.2 Discussion 778
References 779
Part 8: Post Face 780
72: Who Is This Book for? Reserved to Highly Specialized Teams? 781
73: Pulmonary Involvement in Patients with Hematological Malignancies: And Now? 783
Index 785