Chronic and Acute Leukemias in Adults

1. Retroviruses and Onc Genes in Human Leukemias and Lymphomas.- 1.1 Introduction.- 1.2 Onc Genes in Leukemogenesis.- 1.2.1 Introduction.- 1.2.2 Retroviral Derived Cellular Onc Genes.- 1.2.2.1 Genetic Structure of Defective, Acutely Transforming Viruses.- 1.2.2.2 Cellular Origin of the Retroviral Transforming Genes.- 1.2.2.3 Cloning and Properties of the Human Homologues of Retroviral Onc Genes.- 1.2.2.4 Studies of Expression of the Human Homologues of the Viral Onc Genes in Leukemias and Lymphomas.- 1.2.2.5 Amplification as a Mechanism of Activation of Cellular Onc Genes.- 1.2.2.6 Correlation of Onc Gene Localization with Chromosomal Translocations.- 1.2.3 Potential Transformation Genes Detected by Transfection Techniques.- 1.2.3.1 Use of Transfection Techniques to Detect Potential Activated Transforming Genes.- 1.2.3.2 Detection of Activated Ras Onc Gene Family Members by Use of the NIH 3T3 Transfection System.- 1.2.3.3 Detection of an Activated Gene Related to Transferrin in Avian Bursal Lymphomas.- 1.2.3.4 Multiple Genetic Alterations are Required to Transform Normal Diploid Cell Lines that are not Immortalized.- 1.2.3.5 Future Directions in Use of Transfection Systems for Detection of Activated Transforming Genes.- 1.3 Retroviruses in Human Leukemia-Lymphoma.- 1.3.1 Background Considerations.- 1.3.2 Growth of Mature Human T-Cells Growth Factor (TCGF) and the Isolation of the First Human Retroviruses (HTLV).- 1.3.3 Seroepidemiology of HTLV.- 1.3.3.1 Characteristics of HTLV Associated Diseases.- 1.3.3.2 Antibodies to HTLV in the Normal Population and Healthy Relatives of ATL Patients.- 1.3.4 Molecular Epidemiology of HTLV-Related Diseases.- 1.3.5 In Vitro Transformation of Normal Cold Blood T-cells by HTLV.- 1.3.6 Possible Mechanisms for HTLV Transformation.- Acknowledgements.- References.- 2. Study of Differentiation and Proliferation of Leukemic Cells Using Myeloid Leukemia Cell Lines.- 2.1 Introduction: Establishment of Human Myeloid Leukemia Cell Lines.- 2.2 Human Erythroleukemia Cell Lines.- 2.3 Study of Granulocyte Differentiation Using Myeloid Leukemic Cell Lines.- 2.3.1 Nonphysiological Inducers of Granulocyte differentiation.- 2.3.2 Physiological Inducers of Granulocyte Differentiation of HL-60 Cells.- 2.3.2.1 Differentiation Inducing factor.- 2.3.2.2 Retinoids.- 2.3.2.3 Vitamin D Metabolites.- 2.3.2.4 Miscellaneous Physiological Inducers of Myeloid Leukemia Differentiation.- 2.3.3 Therapeutic Implications of Inducers of Granulocyte Differentiation of HL-60.- 2.4 Induction of Macrophage-Like Differentiation of Human Acute Myelogenous Cells.- 2.4.1 Phorbol Diesters.- 2.4.2 Teleocidins.- 2.5 Genetic Analysis of Myeloid Differentiation.- 2.6 Hormonal Modulation of Leukemic Cell Growth.- 2.7 An In Vitro Model for Chemotherapy of Acute Myelogenous Leukemia.- 2.8 Conclusion.- Acknowledgements.- References.- 3. Biological Markers in Lymphoproliferative Disorders.- 3.1 Introduction.- 3.2 Immunological Markers.- 3.2.1 Conventional B and T Markers.- 3.2.2 McAb to B-Cell Antigens.- 3.2.3 McAb Reactive with B and T cells.- 3.2.4 McAb to T-Cell Antigens.- 3.2.5 McAb to Cell’Specific’Antigens.- 3.2.6 T-Functional Assays.- 3.2.7 B-Cell Differentiation In Vitro.- 3.3 Chronic B-Cell Malignancies.- 3.3.1 B-Cell Lymphocytic Leukemia (B-CLL).- 3.3.2 B-Prolymphocytic Leukemia (B-PLL).- 3.3.3 Hairy Cell Leukemia (HCL).- 3.3.4 Non-Hodgkin Lymphomas (NHL).- 3.3.5 Lymphoplasmacytic Lymphoma (LPL).- 3.4 Chronic T-Cell Malignancies.- 3.4.1 T-Chronic Lymphocytic Leukemia (T-CLL).- 3.4.2 T-Prolymphocytic Leukemia (T-PLL).- 3.4.3 Cutaneous T-Cell Lymphomas (CTCL).- 3.4.4 Adult T-Cell Leukemia/Lymphoma (ATTL).- 3.5 Cytochemistry of Acid Hydrolases.- 3.5.1 Acid Phosphatase (AP).- 3.5.2 Alpha-Naphthyl Acetate Esterase (ANAE).- 3.5.3 Dipeptidylaminopeptidase IV (DAP IV).- 3.5.4 Other Acid Hydrolases.- 3.6 Chromosomes.- 3.6.1 Abnormalities in B-CLL.- 3.6.2 Abnormalities in B-PLL.- 3.6.3 Abnormalities in HCL.- 3.6.4 Abnormalities in NHL.- 3.6.5 Abnormalities in T-Cell Leukemias and CTCL.- 3.7 Conclusions.- Acknowledgements.- References.- 4. Surface Marker Analysis of Acute Myeloblasts Leukemia.- 4.1 Introduction.- 4.2 Differentiation of Normal Myeloid Cells.- 4.3 Detection of Myeloid-Lineage Antigens by Heteroantisera.- 4.4 Production of Monoclonal Antibodies to Myeloid Cell Surface Antigens.- 4.5 Monoclonal Antibodies Reactive with Human AML Cells.- 4.5.1 B4.3, B13.9, B2.12.- 4.5.2 B9.8, B13.4, B34.3, B43.4.- 4.5.3 D5.- 4.5.4 D5D6.- 4.5.5 5F1.- 4.5.6 FMC10, FMC11, FMC12, FMC13.- 4.5.7 1G10.- 4.5.8 80H1, 80H3, 80H5.- 4.5.9 L4F3.- 4.5.10 MMA.- 4.5.11 Mo1.- 4.5.12 Mo2.- 4.5.13 Mo3.- 4.5.14 Mo4.- 4.5.15 Mo5.- 4.5.16 My-1.- 4.5.17 My3, My4.- 4.5.18 My7.- 4.5.19 My8.- 4.5.20 My9.- 4.5.21 My10.- 4.5.22 PMN6, PMN29, PM81, and AML-2-23.- 4.5.23 TG1.- 4.5.24 UCHM1, UCHALF.- 4.6 Expression of Myeloid Differentiation Antigens on AML Cells.- 4.6.1 Expression of Myeloid Differentiation Antigens on Cultured Human Myeloid Cell Lines.- 4.6.2 Expression of Myeloid Antigens on Cells From Acute Myeloblasts Leukemia Patients.- 4.6.3 Use of Myeloid Monoclonal Antibodies to Identify Subgroups of AML.- 4.7 Future Directions.- References.- 5. Classification of 358 Cases of Acute Myeloid Leukemia by FAB Criteria: Analysis of Clinical and Morphologic Features.- 5.1 Introduction.- 5.2 Clinical and Morphologic Characteristics of the FAB Classes.- 5.2.1 FAB-M1: Acute Myeloid Leukemia Without Maturation.- 5.2.2 FAB-M2: Acute Myeloid Leukemia With Maturation.- 5.2.3 FAB-M3: Acute Promyelocytic Leukemia.- 5.2.4 FAB-M4: Acute Myelomonocytic Leukemia.- 5.2.5 FAB-M5A: Acute Monocytic Leukemia Poorly Differentiated (Monoblastic).- 5.2.6 FAB-M5B: Acute Monocytic Leukemia with Differentiation.- 5.2.7 FAB-M6: Erythroleukemia.- 5.3 Comparison of FAB Classes of AML.- 5.3.1 Age and Sex Distribution.- 5.3.2 Clinical and Laboratory Findings.- 5.3.3 Morphologic Findings.- 5.3.4 Survival.- 5.4 Discussion.- References.- 6. Chemosensitivity of In Vitro Colony Forming Units as a Predictor of Response to Antileukemic Drugs.- 6.1 Introduction.- 6.2 Colony Assays.- 6.2.1 General Features.- 6.2.2 Colony Assay of Blasts in Acute Myelogenous Leukemia.- 6.2.3 Colony Assay of Blasts in Acute Lymphoblastic Leukemia.- 6.3 Quantitation of Sensitivity to Antileukemic Drugs.- 6.3.1 In Vitro Clonogenic Assays of Drug Sensitivities.- 6.3.2 Differential Sensitivities of Normal and Leukemic Colony Forming Units.- 6.3.3 Effects of Drugs on Capacity for Self-Renewal.- 6.3.4 What is a ‘Drug Resistant’ L-CFU?.- 6.4 Correlations Between In Vitro Chemosensitivities of L-CFU and Clinical Response of the Patient.- 6.4.1 Clinical Drug Resistance.- 6.4.2 Drug Resistance and Treatment Failure.- 6.4.3 L-CFU Assays and Clinical Trails.- 6.4.4 L-CFU Growth In Vitro and Outcome of Therapy.- 6.4.5 Chemosensitivities of L-CFU In Vitro and Outcome of Therapy.- 6.5 Summary.- References.- 7. Post-Remission Therapy for Acute Myelogenous Leukemia.- 7.1 Introduction.- 7.2 Role of Induction Therapy on Remission Duration.- 7.3 Role of Consolidation Therapy on Remission Duration.- 7.4 Role of Maintenance Chemotherapy in Prolonging Remissions.- 7.5 The Role of Immunotherapy in Maintenance.- 7.6 Prognostic Variables Predicting for Prolonged Remission Duration.- 7.7 Central Nervous System Leukemia.- 7.8 Bone Marrow Transplantation.- 7.9 Summary and Conclusions.- Acknowledgement.- References.- 8. The Role of Marrow Transplantation in the Treatment of Leukemia.- 8.1 Introduction.- 8.2 Donor Selection.- 8.3 Preparative Regimens.- 8.4 Techniques of Marrow Transplantation.- 8.5 Clinical Results in Acute Nonlymphoblastic Leukemia (ANL).- 8.5.1 Refractory ANL.- 8.5.2 First Remission of ANL.- 8.5.3 After First Relapse.- 8.5.4 The Role of Transplantation in ANL.- 8.6 Clinical Results in Acute Lymphoblastic Leukemia (ALL).- 8.6.1 Refractory ALL.- 8.6.2 Remission ALL.- 8.6.3 The Role of Transplantation in ALL.- 8.7 Clinical Results in Chronic Granulocytic Leukemia (CGL).- 8.7.1 CGL Blast Crisis.- 8.7.2 CGL in Chronic Phase.- 8.7.3 The Role of Transplantation in CGL.- 8.8 Leukemic Recurrence After Transplantation.- 8.9 Graft-Versus-Host Disease (GVHD).- 8.9.1 Acute GVHD.- 8.9.2 Chronic GVHD.- 8.9.3 Graft-Versus-Leukemia.- 8.10 Infectious Complications, Including Interstitial Pneumonia.- 8.11 Other Organ Toxicities.- 8.11.1 Cardiac.- 8.11.2 Hepatic.- 8.11.3 Gonadal Function.- 8.12 Summary.- Acknowledgements.- References.- 9 Hyperleukemias in Adult Leukemia.- 9.1 Introduction.- 9.2 Acute Myelocytic Leukemia.- 9.2.1 Central Nervous System Leukemia.- 9.2.2 Lung Involvement.- 9.2.3 Therapy.- 9.3 Chronic Myelocytic Leukemia.- 9.3.1 Central Nervous System.- 9.3.2 Lung Involvement.- 9.3.3 Therapy.- 9.4 Acute Lymphocytic Leukemia.- 9.4.1 Introduction.- 9.4.2 Review of the Literature.- 9.4.3 Therapy.- 9.4.4 Mount Sinai Hospital Experience.- Acknowledgement.- References.- 10 New Developments in the Etiology, Diagnosis, Treatment and Prevention of Infectious Complications in Patients with Leukemia.- 10.1 Introduction.- 10.2 Changing Patterns of Infections.- 10.2.1 Bacteria.- 10.2.2 Fungi.- 10.2.3 Mycrobacteria and Nocardia.- 10.2.4 Viruses.- 10.3 New Developments in Evaluation and Diagnosis.- 10.3.1 Nuclear Imaging.- 10.3.2 Serodiagnosis.- 10.3.3 Surveillance Cultures.- 10.4 Developments in Antimicrobial Therapy.- 10.4.1 Empiric Antibiotic Therapy.- 10.4.2 The Patient with Continued Fever and Granulocytopenia.- 10.5 New or Evolving Syndromes in Management of Infections in the Adult Leukemic.- 10.5.1 Foreign Bodies.- 10.5.2 Antibiotic Modifications (Broad vs Specific Therapy).- 10.5.3 Management of Oral Complications.- 10.5.4 Esophagitis.- 10.5.5 Management of Pulmonary Infiltrates.- 10.5.6 Unique Gastrointestinal Pathogens.- 10.5.7 Perirectal Cellulitis and Abscess.- 10.5.8 Rhinocerebral Syndrome.- 10.6 Recent Developments in Adjuvant Therapy.- 10.6.1 Granulocyte Transfusions.- 10.6.2 Immunoglobulins.- 10.6.3 Immune Adjuvants.- 10.7 Current Concepts in Infection Prevention in Acute Leukemia.- 10.7.1 Isolation.- 10.7.1.1 Reverse Isolation.- 10.7.1.2 Total Protected Environment.- 10.7.2 Antibiotic Prophylaxis.- 10.7.2.1 GI Decontamination.- 10.7.2.2 Selective Decontamination.- 10.7.2.3 Monoprophylaxis.- 10.7.2.4 Specific Antimicrobial Prophylaxis.- 10.7.2.5 Recommendations Regarding Antibiotic Prophylaxis.- 10.7.4 Granulocyte Transfusions.- 10.7.5 Summary.- References.