Concise Manual of Hematology and Oncology, 1st Edition

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Editors
D. P. Berger, M. Engelhardt, H. Henß, R. Mertelsmann

Co-Editors
M. Andreeff, B. Koziner, H. A. Messner, N. Thatcher

Concise Manual
of Hematology and Oncology

With 138 Figures and 474 Tables

123
Editors
Dietmar P. Berger Co-Editors
University Medical Center Michael Andreeff
Department of Hematology and Oncology MD Anderson Cancer Center
Hugstetter Strasse 55 1515 Holcombe Boulevard 081
79106 Freiburg, Germany Houston, TX 77030-4095, USA

Monika Engelhardt Benjamin Koziner

University Medical Center Unitad de Investigaciones
Department of Hematology and Oncology Oncohematologicas
Hugstetter Strasse 55 Laboratorio ‘Nelly Arrieta de Blaquier’
79106 Freiburg, Germany Agrelo 3038
Buenos Aires C.P. 1221, Argentinia
Hartmut Henß
Tumorzentrum Ludwig-Heilmeyer Hans A. Messner
Comprehensive Cancer Center Princess Margaret Hospital
University Medical Center 5th Floor, Room 107
Hugstetter Strasse 55 610 University Avenue
79106 Freiburg, Germany Toronto, ON M5G 2M9, Canada

Roland Mertelsmann Nick Thatcher

University Medical Center Department of Medical Oncology
Department of Hematology and Oncology Christie Hospital NHS Trust
Hugstetter Strasse 55 Wilmslow Road
79106 Freiburg, Germany Manchester M20 4BX, United Kingdom

We would like to thank Dr. Milena Pantic and Dr. Ralph Wäsch for kindly providing the
figures used for the cover.

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Preface

How Do We Treat?

Hematology and Oncology have seen rapid progress and advances during recent years.
Increased knowledge of tumor biology, epidemiology, molecular genetics, growth regu-
lation, and cellular functions has led to novel therapeutic paradigms. Targeted treat-
ment approaches, antibodies, immunotherapy, and other new techniques complement
classic chemotherapy, radiotherapy, and surgery. Patients are increasingly well educated
as web-based information on diagnostic and therapeutic options as well as quality man-
agement and tumor outcome data are readily available.

In this dynamic and fast-paced environment, it is of central importance to base clinical

decisions and medical practice on the best available evidence. Continuous quality man-
agement, with clinical process documentation, standardization, and evaluation, leads to
improved patient care and long-term outcomes. For these reasons, we have started to
systematically capture and evaluate data on diagnosis, treatment, and outcomes of pa-
tients with solid tumors and hematological neoplasms at the Freiburg University Medi-
cal Center. We have developed standard operating procedures, clinical pathways, and
diagnostic and therapeutic processes, following the principles of “Good Clinical Prac-
tice.” These processes (e.g., detailed protocols for chemotherapy application, treatment
flowcharts, clinical pathways) are continuously tested and validated in clinical practice.
National and international guidelines, new clinical study data, and international expert
advice are incorporated into a framework of clinical standards. Based on this work, the
Freiburg University Medical Center and the Comprehensive Cancer Center Freiburg
have been recognized as one of the centers of excellence in hematology and oncology in
Germany and Europe.

The Concise Manual of Hematology and Oncology is the result of this continuous pro-
cess. It offers a specific view based on the daily practice at a large European academic
medical center, and we welcome any comments and discussion. Several German lan-
guage editions of the manual have been published since 1998, and we are thankful for all
the positive feedback and constructive criticism we received. With the first English edi-
tion, we again want to support practicing physicians and healthcare providers in their
daily interaction with patients in hematology and oncology. Treatment of patients with
malignant diseases is always a challenge, in curative, supportive, and palliative settings,
and each patient—in his or her unique situation—deserves the best available therapy
and care.

The Editors
March 2008
Contents

1 Principles of Medical Oncology

1.1 Epidemiology .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Carcinogenesis, Molecular Tumor Biology .. . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 Hematopoiesis and Development of Hematological Neoplasia .. . . . . . . . 7
1.4 Prevention and Screening .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.5 Classification of Diseases and ICD System . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.6 Tumor Classification and TNM System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.7 Indications for Tumor Therapy .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.8 Performance Status of Tumor Patients (“Performance Status Scales”) . . 21
1.9 Response Evaluation in Solid Tumors .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.10 Common Toxicity Criteria (NCI) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
1.11 Assessing the Quality of Life of Tumor Patients . . . . . . . . . . . . . . . . . . . . . . 30
1.12 Evidence-based Medicine (EBM), Guidelines and Quality
Management .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
1.13 Electronic Media .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

2 Special Diagnostics
2.1 Cytogenetics and Fluorescence In Situ Hybridization (FISH) .. . . . . . . . . 39
2.2 Molecular Diagnosis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.3 Gene Expression Analysis using Microarrays .. . . . . . . . . . . . . . . . . . . . . . . . 45
2.4 Tumor Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.5 CD Antigens and Immunocytological Diagnosis . . . . . . . . . . . . . . . . . . . . . 51
2.6 HLA System and MHC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

3 Pharmacology and Pharmacotherapy

3.1 Basic Principles of Chemotherapy .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    65
3.2 Cytostatic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    69
3.2.1 Characteristics of Clinically Used Cytostatic Drugs .. . . . . . . . . . . . . . . . . .    71
3.2.2 Check List Cytostatic Treatment .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
3.2.3 Drug Dosage Calculation Based on Body Surface Area (BSA) . . . . . . . . . 132
3.2.4 Dose Adjustment of Cytostatic Drugs .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
3.2.5 Chemotherapy During Pregnancy and Lactation . . . . . . . . . . . . . . . . . . . . . 141
3.2.6 Selected Cytostatic Drug Incompatibilities .. . . . . . . . . . . . . . . . . . . . . . . . . . 143
3.2.7 Preparation and Stability of Cytostatics .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
3.3 Hormone Therapy .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
3.3.1 Characterization of Hormone Treatments in Oncology . . . . . . . . . . . . . . . 156
3.4 Cytokines .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
3.5 Monoclonal Antibodies .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
3.6 Specific Protein Kinase Inhibitors (“Targeted Therapies”) . . . . . . . . . . . . . 188
3.7 Drug Development and Clinical Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
3.8 Pharmacogenetics and Pharmacogenomics . . . . . . . . . . . . . . . . . . . . . . . . . . 201

4 Supportive Treatment
4.1 Antiemetic Prophylaxis and Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
4.2 Antibiotic Treatment and Neutropenic Fever .. . . . . . . . . . . . . . . . . . . . . . . . 211
Contents

4.3 Growth Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218

4.4 Nutrition in Cancer Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.4.1 Malnutrition in Cancer Patients .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
4.4.2 Parenteral Nutrition .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
4.5 Pain Control .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
4.6 Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
4.7 Bisphosphonates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
4.8 Malignant Effusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
4.8.1 Malignant Pleural Effusion .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
4.8.2 Malignant Pericardial Effusion .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
4.8.3 Malignant Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
4.9 Transfusion Therapy .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
4.9.1 Cellular Blood Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
4.9.2 Non-cellular Blood Products .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
4.10 Human Sperm Cryopreservation .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
4.11 Cryopreservation of Human Pronuclear Oocytes .. . . . . . . . . . . . . . . . . . . . 274
4.12 Sexual Dysfunction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
4.13 Physiotherapy and Sports Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
4.14 Principles of Oncology Nursing Care .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
4.15 Psycho-oncological Care .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
4.16 Rehabilitation .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289

5 Particular Treatment Procedures

5.1 Hematopoetic Stem Cell Technology (Harvesting, Culture, Purging) . . 293
5.2 Autologous Hematopoetic Stem Cell Transplantation .. . . . . . . . . . . . . . . . 296
5.3 Allogeneic Hematopoetic Stem Cell Transplantation .. . . . . . . . . . . . . . . . . 302
5.4 Granulocyte Transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
5.5 Immunotherapy .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
5.6 Gene Therapy .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
5.7 Inhibition of Angiogenesis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
5.8 Developmental Therapeutics .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322

6 Hematology and Hemostasis

6.1 Aplastic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
6.2 Neutropenia and Agranulocytosis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
6.3 Thrombocytopenia .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
6.3.1 Immune (Idiopathic) Thrombocytopenic Purpura
(ITP, Werlhof ’s Disease) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
6.3.2 Heparin-induced Thrombocytopenia (HIT) .. . . . . . . . . . . . . . . . . . . . . . . . . 343
6.3.3 Thrombotic Microangiopathies (TTP-HUS) . . . . . . . . . . . . . . . . . . . . . . . . . 345
6.4 Anemia .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348
6.4.1 Hypochromic Anemia .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
6.4.2 Megaloblastic Anemia .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
6.4.3 Hemolytic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
6.4.4 Normochromic Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
6.5 Coagulation Disorders .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
6.5.1 Acquired Coagulation Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
6.5.2 Factor VIII Deficiency (Hemophilia A) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381

VIII
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6.5.3 Factor IX Deficiency (Hemophilia B) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384

6.5.4 Von Willebrand’s Disease (VWD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
6.5.5 Disseminated Intravascular Coagulation (DIC) . . . . . . . . . . . . . . . . . . . . . . 389
6.6 Thromboembolism and Thrombophilia .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393

7 Hematological Neoplasia
7.1 Acute Leukemias .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
7.1.1 Acute Lymphoblastic Leukemia (ALL) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
7.1.2 Acute Myeloid Leukemia (AML) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
7.2 Myelodysplastic Syndrome (MDS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
7.3 Myeloproliferative Disorders (MPD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429
7.3.1 Chronic Myeloid Leukemia (CML) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
7.3.2 Polycythemia Vera . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
7.3.3 Essential Thrombocythemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
7.3.4 Chronic Idiopathic Myelofibrosis (CIMF) .. . . . . . . . . . . . . . . . . . . . . . . . . . . 447
7.4 Hodgkin’s Disease (Hodgkin’s Lymphoma) .. . . . . . . . . . . . . . . . . . . . . . . . . . 450
7.5 Non-Hodgkin’s Lymphomas (NHL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461
7.5.1 High-grade Non-Hodgkin’s Lymphoma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
7.5.2 Chronic Lymphocytic Leukemia (CLL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473
7.5.3 Prolymphocytic Leukemia (PLL) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480
7.5.4 Hairy Cell Leukemia (HCL) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
7.5.5 Follicular Lymphoma (FL) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486
7.5.6 Mantle Cell Lymphoma (MCL) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
7.5.7 Primary Cutaneous T-cell Lymphoma (CTCL) . . . . . . . . . . . . . . . . . . . . . . . 495
7.5.8 Primary Lymphoma of the Central Nervous System (CNS) .. . . . . . . . . . . 501
7.5.9 Marginal Zone Lymphoma (MZL) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505
7.5.10 Multiple Myeloma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
7.5.11 Immunocytoma (Waldenström’s Macroglobulinemia) . . . . . . . . . . . . . . . . 518
7.6 Langerhans Cell Histiocytosis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521
7.7 Mastocytosis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525

8 Medical Oncology
8.1 Head and Neck Tumors .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
8.2 Tumors of the Respiratory System .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
8.2.1 Lung Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
8.2.2 Mesotheliomas .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548
8.2.3 Mediastinal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 552
8.3 Gastrointestinal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
8.3.1 Esophageal Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
8.3.2 Gastric Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562
8.3.3 Cancer of the Small Intestine .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 568
8.3.4 Colorectal Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572
8.3.5 Anal Carcinoma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579
8.3.6 Pancreatic Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
8.3.7 Hepatocellular Carcinoma (HCC) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589
8.3.8 Tumors of the Gallbladder and Bile Duct . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595
8.4 Tumors of the Female Reproductive System .. . . . . . . . . . . . . . . . . . . . . . . . . 599
8.4.1 Breast Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599

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8.4.2 Malignant Ovarian Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613

8.4.3 Malignant Germ Cell Tumors in Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621
8.4.4 Granulosa Cell Tumors of the Ovary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 625
8.4.5 Sertoli-Leydig Cell Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 628
8.4.6 Malignant Trophoblastic Tumors .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 630
8.4.7 Cervical Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635
8.4.8 Endometrial Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 642
8.4.9 Uterine Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 648
8.4.10 Vaginal Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 651
8.4.11 Vulvar Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 654
8.5 Tumors of the Male Reproductive System .. . . . . . . . . . . . . . . . . . . . . . . . . . . 658
8.5.1 Testicular Tumors .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 658
8.5.2 Extragonadal Germ Cell Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667
8.5.3 Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671
8.5.4 Penile Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 680
8.6 Tumors of the Urinary Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684
8.6.1 Renal Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684
8.6.2 Tumors of the Renal Pelvis, Ureter, and Bladder .. . . . . . . . . . . . . . . . . . . . . 690
8.7 Tumors of the Endocrine System .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698
8.7.1 Thyroid Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698
8.7.2 Neuroendocrine Tumors (NET) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 704
8.7.3 Malignant Pheochromocytoma and MEN .. . . . . . . . . . . . . . . . . . . . . . . . . . . 711
8.7.4 Tumors of the Adrenal Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 715
8.7.5 Pituitary Gland Tumors .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 718
8.8 Malignant Tumors of the Skin .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 721
8.8.1 Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 721
8.8.2 Basal Cell Carcinoma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 729
8.8.3 Squamous Cell Carcinoma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731
8.8.4 Merkel Cell Carcinoma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 734
8.9 Sarcomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 737
8.9.1 Soft Tissue Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 737
8.9.2 Gastrointestinal Stromal Tumor (GIST) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 742
8.9.3 Primitive Neuroectodermal Tumors (PNET) and Ewing’s Sarcoma . . . . 744
8.9.4 Osteosarcoma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
8.10 CNS Tumors .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 753
8.11 Cancer of Unknown Primary (CUP) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 758
8.12 Metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
8.12.1 Brain Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 764
8.12.2 Carcinomatous Meningitis (Leptomeningeal Metastases) . . . . . . . . . . . . . 766
8.12.3 Lung Metastases .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770
8.12.4 Liver Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
8.12.5 Bone Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774
8.13 Paraneoplastic Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 776

9 Hematological and Oncological Emergencies

9.1 Neutropenic Sepsis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 783
9.2 Superior Vena Cava Syndrome (SVCS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 785
9.3 Spinal Cord Compression / Cauda Equina Syndrome .. . . . . . . . . . . . . . . . 787


 Contents

9.4 Malignant Cardiac Tamponade .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 789

9.5 Malignant Hypercalcemia .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791
9.6 Tumor Lysis Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 793
9.7 Hemorrhagic Complications / Malignant Vascular Erosion . . . . . . . . . . . 795
9.8 Transfusion Reactions .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797
9.9 Extravasation of Cytostatic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 801

10 Standard Operating Procedures (SOP)

10.1 Thoracentesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 804
10.2 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 806
10.3 Abdominal Paracentesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 808
10.4 Bone Marrow Aspiration and Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 810
10.5 Basic Hematological Diagnostics .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
10.6 Lumbar Puncture (Spinal Tap) and Intrathecal Instillation
of Cytostatic Drugs .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 818
10.7 Central Venous Access (CVA), Central Venous Catheter (CVC) .. . . . . . 820
10.8 Blood Cultures .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 823

11 Standardized Treatment Protocols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 825

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 993

XI
Abbreviations

A. Arteria DDAVP Desamino-D-Arginin- Vasopressin

Aa. Arteriae (Desmopressin)
Ab Antibody Def Definition
abs. absolute (ly) DFS Disease free survival
Ad Adresses DFI Disease free interval
Ag Antigen Dg Diagnostic
AIDS Aquired Immune Deficiency Di Drug interaction
Syndrome DIC Disseminated intravasal
AIHA Autoimmune Hemolytic Anemia Coagulation
AJCC American Joint Committee on dl Deciliter (100 ml)
Cancer DNA Deoxyribonucleic Acid
AML Acute myeloid Leukemia Dos Dosing
ANA Antinuclear Antibodies
ALL Akuce lymphaticLeukemia EBV Epstein Barr Virus
a.o. among others ECOG Eastern Cooperative Oncology
ARDS Acute Respiratory Distress Group (ECOG Performance Scale)
Syndrome ECG Elektrocardiogram
ATIII Antithrombin III e.g. for instance
ATTN Attention, be careful, EORTC European Organisation for
Research and Treatment of Cancer
B Bolus injection Ep Epidemiology
BC Blood Count ES Extrasystoles
BCh Biochemistry ESR Erythrocyte Sedimentation Rate
BM Bone marrow Et Etiology
BW Body weight etc. et cetera
BSA Body surface area
F Factor (Clotting factors FI to FXIII)
°C Degree Celsius FBC Full Blood Count
Ca2+ Calcium FIGO International Federation of
CD Cluster of Differentiation Gynecology and Obstetrics
CFU Colony Forming Units F/U Follow Up
Chap. Chapter
Chem Chemistry g Gram
Ci. Contraindication GFR Glomerular Filtration Rate
c.i.v. continuous intravenous GvHD Graft versus Host Disease
Cl- Chloride GvL Graft versus Leukemia
Class Classifikation
CLL Chronic lymphatic Leukemia h hour(s) (hora)
CML Chronische myeloid Leukemia HAT Heparin-associated Thrombopenia
CMV Cytomegalie Virus HAV Hepatitis A Virus
CNS Central nervous system Hb Hemoglobin
Co Complications HBV Hepatitis B Virus
CRP C-reactive Protein HCV Hepatitis C Virus
CSF CerebroSpinal Fluid hd high dose
CT Computed tomography HIV Human Immunodeficiency Virus
CVC Central Venous Catheter Hkt Hematocrit
CVL Central Venous Line HSV Herpes Simplex Virus
CVP Central Venous Pressure HUS Hemolytic-uremic Syndrom

d day(s) (dies) i.a. Intraarterial

DCCL Diffuse Large Cell Lymphoma i.m. Intramuscular
Dd Differential diagnosis i.p. intraperitoneal
Ddi Drug drug interaction i.t. Intrathecal
Abbreviations

i.v. Intravenous Pharm Pharmacology

ICD-10 International Classification Phys Physiology
of Diseases (10. edition) PKin Pharmacokinetics
Ig Immunglobulin(e) Phys Physiology
Ind Indication PNH Paroxysmal Nocturnal
ITP Idiopathic thrombocytopenic Hemoglobinuria
Purpura PPhys Pathophysiology
IU International Units PPSB Prothrombin Complex Concentrate
Prg Prognosis
K+ Kalium PT Prothrombin Time
kDa kilo Dalton PTT Partial Prothromin Time
kg Kilogramm Px Prophylaxis

l Liter ® registered trade mark

LDH Lactate dehydrogenase RFA Radio frequency ablation
LFT Liver Function Tests RNA Ribonucleic Acid
Lit Literature Ref references
LMWH Low Molecular Weight Heparin RT Radiotherapy
Ln Lymph nodes
LPHD Lymphocyte Predominant s seconds
Hodgkin’s Disease s.c. subcutaneous
SCC Squamous Cell Cancer
M. Morbus Se Side effects
MALT mucosa associated lymphoid tissue SLE Systemic Lupus erythematodes
MDS Myelodysplastic Syndrome(s) SOP Standard Operating Procedure,
Meth Methods Stag Staging
mg Milligram SVES supraventricular Extasystoles
µg Microgram Sy Symptoms
Mg2+ Magnesium
MGUS Monoclonal Gammopathy t½ Half life time
of Unknown Significance TBI Total Body Irradiation
min Minute(s) TBC Tuberculosis
ml Milliliter Th Treatment, Therapy
µl Microliter TNM TNM-System, Tumor classifikation
MOA Mechanism of Action (defines T = Tumor, N = Lymph
MPS Myeloproliferative nodes and M = Metastases)
Syndrome(s) TRALI Transfusion Associated Lung Injury
MW Molecular weight TT
TTP Thrombotic-thrombozytopenic
Na+ Sodium Purpura
NCI National Cancer Institute
NHL Non-Hodgkin-Lymphoma U Units
NMR Nuclear Magnetic Resonance U&E Urine and Electrolytes
Tomography UICC Union Internationale Contre
le Cancer
Path Pathology UFH Unfractionated Heparin
PBCh Pathobiochemistry
PBSCT Peripheral Blood Stem Cell V. Vena
Transplantation VES ventricular Extrasystoles
PCP Pneumocystis Carinii Pneumonia Vv. Venae
PCR Polymerase Chain Reaction VZV Varizella Zoster Virus
PET Positron Emission Tomography
Persp. Perspective WHO World Health Organisation
Pg Pathogenesis Web Internet adresses

XIV
 Abbreviations

Special symbols Additional Abbreviations are explained

α Alpha in the respective chapters
β Beta
γ Gamma
δ Delta
κ Kappa
λ Lambda
µ Mu, Micro
→ leading to
↑ increased
↓ lowered, decreased
> larger than, more frequent than
< smaller than, less frequent as
> larger or equal
< smaller or equal
≈ about
♀ women, female
♂ men, male
► see (refers to other chapter)
 phone

XV
Contributors

Adam, Gerhard Burger, Jan

Asklepios Klinik Triberg MD Anderson
Fachklinik f. Innere Medizin PO Box 301402
Hematologie/Onkologie Houston, TX 77230-1402, USA
Ludwigstrasse 1-2
78098 Triberg, Germany Burger, Meike
University Medical Center
Allgaier, H.-P. Department of Hematology and Oncology
Deaconness Hospital Hugstetter Strasse 55
Wirthstrasse 11 79106 Freiburg, Germany
79110 Freiburg, Germany
Daskalakis, Michael
Andreeff, Michael University Medical Center
MD Anderson Cancer Center Department of Hematology and Oncology
1515 Holcombe Boulevard 081 Hugstetter Strasse 55
Houston, TX 77030-4095, USA 79106 Freiburg, Germany

Behringer, D. Deschler, Barbara

Augusta-Kranken-Anstalt University Medical Center
Hematology, Oncology Department of Hematology and Oncology
Bergstrasse 26 Hugstetter Strasse 55
44791 Bochum, Germany 79106 Freiburg, Germany

Berger, Dietmar P. Digel, Werner

University Medical Center University Medical Center
Department of Hematology and Oncology Department of Hematology and Oncology
Hugstetter Strasse 55 Hugstetter Strasse 55
79106 Freiburg, Germany 79106 Freiburg, Germany

Bertz, Hartmut Engelhardt, Andrea

University Medical Center University Medical Center
Department of Hematology and Oncology Department of Hematology and Oncology
Hugstetter Strasse 55 Hugstetter Strasse 55
79106 Freiburg, Germany 79106 Freiburg, Germany

Blattmann, Ursula Engelhardt, Monika

University Medical Center University Medical Center
Central Physiotherapy Department of Hematology and Oncology
Department of Internal Medicine Hugstetter Strasse 55
Hugstetter Strasse 55 79106 Freiburg, Germany
79106 Freiburg, Germany
Contributors

Engelhardt, Rupert Harder, Jan

University Medical Center University Medical Center
Department of Hematology and Oncology Department of Gastroenterology
Hugstetter Strasse 55 Hepatology, Endocrinology
79106 Freiburg, Germany and Infectious Diseases
Hugstetter Strasse 55
Fetscher, Sebastian 79106 Freiburg, Germany
Sana Kliniken Lübeck
Klinik für Hämatologie/Onkologie Heeskens, Katrin
Städt. Krankenhaus Süd Blumhardtstrasse 17
Kronsforder Allee 71/73 75378 Bad Liebenzell, Germany
23560 Lübeck, Germany
Heining-Mikesch, Kristina
Finke, Jürgen University Medical Center
University Medical Center Department of Hematology and Oncology
Department of Hematology and Oncology Hugstetter Strasse 55
Hugstetter Strasse 55 79106 Freiburg, Germany
79106 Freiburg, Germany
Heinz, Jürgen
Frank, Uwe University Medical Center
University Medical Center Department of Hematology and Oncology
Department of Environmental Medicine Hugstetter Strasse 55
and Hygiene 79106 Freiburg, Germany
Hugstetter Strasse 55
79106 Freiburg, Germany Henne, Karl
University Medical Center
Gärtner, Frank Department of Radiation Therapy
University Medical Center Hugstetter Strasse 55
Department of Hematology and Oncology 79106 Freiburg, Germany
Hugstetter Strasse 55
79106 Freiburg, Germany Henß, Hartmut
Tumorzentrum Ludwig-Heilmeyer
Göbel, Alexandra Comprehensive Cancer Center
University Medical Center University Medical Center
Hospital Pharmacy Hugstetter Strasse 55
Hugstetter Strasse 55 79106 Freiburg, Germany
79106 Freiburg, Germany
Houet, Leonora
Gölz, Tanja University Medical Center
University Medical Center Department of Hematology and Oncology
Department of Hematology and Oncology Hugstetter Strasse 55
Hugstetter Strasse 55 79106 Freiburg, Germany
79106 Freiburg, Germany
Illerhaus, Gerald
Grüllich, Carsten University Medical Center
University Medical Center Department of Hematology and Oncology
Department of Hematology and Oncology Hugstetter Strasse 55
Hugstetter Strasse 55 79106 Freiburg, Germany
XVIII
79106 Freiburg, Germany