Acute Leukemias IV : Prognostic Factors and Treatment Strategies

The rates of acute leukemia cure have gradually improved over the last decade. Clinical study results reflect the impact of chemotherapy intensity and duration, the role of prolonged maintenance, intensified consolidation or very early intensification. Further progress has also been achieved in bone marrow trans­ plantation, and recent prospective studies and meta-analyses have contributed comparisons of the high antileukemic efficacy of bone marrow transplantation to that of improved chemotherapy. This allows a more successful combining of the two forms of treatment. New prognostic factors have emerged from both cytogenetic and molecular genetic research. Thus, the Philadelphia chromosome translocation and the bcr/abl gene rearrangement have proven to be the dominating risk factor in acute lymphoblastic leukemia. Since the frequency increases with age, differences in prognosis between children and adults can be explained. Evaluation of molecular and immunologic leukemia cell markers has provided a better understanding of residual leukemia in clinical remission, as a prognostic factor and in monitoring the effectiveness of the antileukemic strategy. Recent work on leukemic cell biology has resulted in novel therapeutic approaches such as terminal differentiation by all-trans-retinoic acid, modulation of chemotherapy by hematopoietic growth factors such as GM-CSF and enhancement of immunologic control by cytokines such as interleukin 2. New antimicrobial drugs and the application of mostly empiric anti-infectious strategies have helped reducing the therapeutic risk. Thus, a number of recent achievements have provided us with new options in the management of patients with acute leukemias. Front Matter....Pages I-XXXVI The Treatment of Acute Leukemia: Observations by a Marrow Transplanter....Pages 1-5 Front Matter....Pages 7-7 Polymerase Chain Reaction Approach for the Evaluation of Minimal Residual Disease in Acute Leukemia....Pages 9-14 Two Subtypes of Therapy-Related Leukemia; Experience from The Copenhagen Series....Pages 15-23 Incidence, Biologic Features and Treatment Outcome of Myeloid-Antigen-Positive Acute Lymphoblastic Leukemia (My + ALL)....Pages 24-32 In Situ Amplification of Rearranged Gene Sequences in Individual Cells for Tracing Clonal Cells in Smears from Blood and Bone Marrow....Pages 33-37 Detection of Chromosomal Abnormalities on Previously Stained Peripheral Blood and Bone Marrow Smears....Pages 38-42 Interphase Cytogenetics of Childhood Acute Lymphoblastic Leukemia with Fluorescence In Situ Hybridization Using a Panel of Eight Chromosome-Specific DNA Probes....Pages 43-46 Identification and Characterization of Monoclonal Lymphoid Populations by Analysis of Complementary RNA of Clonespecific DNA Sequences....Pages 47-50 Differences in Immunoglobulin and T-Cell Receptor Gene Rearrangement Patterns in Acute Lymphoblastic Leukemia Between Diagnosis and Relapse....Pages 51-58 Characterization of Clonal Gene Rearrangements for the Detection of Residual Leukemic Disease in Acute Lymphoblastic Leukemia....Pages 59-64 Analysis of Variable Number of Tandem Repeats Reveals Differences Between Leukemic Cells and Remission Phase Leukocytes....Pages 65-70 The tal-1 Gene Rearrangement in Acute Lymphoblastic Leukemia....Pages 71-74 Significance of Lineage-Associated Transcripts of TdT and ETS1 for Detection of Leukemic Cells....Pages 75-80 Mutations of the P53 Gene in Acute Leukemias: A Report on 207 Cases....Pages 81-84 Regulation of the Expression of ICAM-1 on Pre-B Cell Lines by TNF-α and IFN-γ....Pages 85-89 Modulation of Adhesion Molecules in Patients with AML During Immunotherapy with IL-2....Pages 90-95 Frequency of Aberrant Surface Marker Expression in 221 Cases of Adult Acute Leukemia: An Immunologic/Cytogenetic Analysis....Pages 96-101 Elevated Plasma Neuropeptide Y as a Marker of B Cell Precursor Leukemia in Children....Pages 102-105 Clinical Applications of Stromal Cell Studies in Acute Leukemia....Pages 106-109 Effects of TNF α on AML Cells Determined by Flow Cytometric Technique Based on Bromodeoxyuridine Incorporation....Pages 110-115 Front Matter....Pages 7-7 In Vitro Isolation of Human Cytotoxic Clones Specific for Autologous Leukemic Blasts....Pages 116-120 Lymphocyte Subsets and IL-1 Production in Children with Acute Lymphoblastic Leukemia During Intensive Chemo- and Radiotherapy....Pages 121-126 Front Matter....Pages 127-127 Treatment Strategy of Acute Promyelocytic Leukemia Using All Trans Retinoic Acid....Pages 129-132 Modulation of Ara-C Metabolism by Fludarabine: Therapy for Acute Myelogenous Leukemia....Pages 133-137 GM-CSF in Chemotherapy for Newly Diagnosed AML: Multiple Course Priming and Longterm Administration Compared to Chemotherapy Alone....Pages 138-141 Front Matter....Pages 143-143 Pharmacokinetic Aspects of Etoposide Therapy — A Review....Pages 145-153 Clinical Pharmacokinetics of VP-16 — Special Aspects in Children....Pages 154-158 DEXA-BEAM Salvage Chemotherapy and High-Dose Chemotherapy Followed by Autologous Bone Marrow Transplantation in Hodgkin’s Disease....Pages 159-164 Chronic Etoposide Schedules in the Treatment of Non-Hodgkin’s Lymphoma....Pages 165-171 Etoposide (VP-16) Disposition in Children with Acute Myeloblastic Leukemia....Pages 172-174 Myeloablative Regimens Containing High Dose Etoposide Followed by Allogeneic or Autologous Bone Marrow Transplantation for Hematologic Malignancies....Pages 175-178 Front Matter....Pages 179-179 Effects on Ara-C Cytotoxicity for AML Colony Forming Cells By Priming With rhGM-CSF and rhIL-3 In Vitro and In Vivo....Pages 181-184 Myelodysplastic Syndromes: Treatment Indication and Choice of Therapy....Pages 185-200 Autologous Bone Marrow Transplantation for Lymphoid Malignancies: The Use of Hematopoietic Growth Factors....Pages 201-204 Front Matter....Pages 205-205 Long-Term Results on Mitoxantrone Treatment in Patients with Low-Grade Non-Hodgkin’s Lymphomas....Pages 207-210 Comparison of Prednimustine/Mitoxantrone (PmM) and Cyclophosphamide/Vincristine/Prednisolone (COP) in Patients with Low-Grade Non-Hodgkin Lymphomas Followed by Interferon α Maintenance....Pages 211-215 Mitoxantrone, Etoposide and Cytarabine in the Treatment of Acute Myelocytic Leukemia (AML)....Pages 216-220 Mitoxantrone Pharmacokinetics....Pages 221-230 Improving the Remission Quality in Acute Myelogenous Leukemia (AML) by Increasing Cytoreduction During Induction Therapy....Pages 231-234 Treatment of Relapsed and Refractory AML with Mitoxantrone and Etoposide: A Study of the Eastern Cooperative Oncology Group....Pages 235-238 Front Matter....Pages 239-239 Vitamin A Does Not Enhance the Antileukemic Effect of Vincristine, Daunorubicin, and 6-Thioguanine in Acute Lymphoblastic Leukemia Cells....Pages 241-244 Reversal of Multidrug Resistance by R-Verapamil....Pages 245-249 Multidrug Resistance in Myelodysplastic Syndromes and Acute Leukemia....Pages 250-253 Combinations of Cytostatic Drugs with Calcium/Calmodulin Antagonists for Reversal of Multidrug Resistance....Pages 254-257 Modulation of Intracellular Ara-C Metabolism in AML Blasts by GM-CSF....Pages 258-269 Clinical Relevance of the Influence of Etoposide on Ara-CTP Formation in Leukemic Blast Cells....Pages 270-272 Resistance to Cytosine Arabinoside: Are Mutations in CTP Synthetase an Important Mechanism?....Pages 273-276 Inhibitory Effect of 2′,2′-Difluorodeoxycytidine on Cytidine 5′-Triphosphate Synthetase....Pages 277-280 Antileukemic Activity In Vitro of Mitoxantrone and Anthracyclines in Untreated Childhood Acute Lymphoblastic Leukemia....Pages 281-285 Childhood Acute Lymphoblastic Leukemia and Acute Non-Lymphoblastic Leukemia: Differences in Cellular Drug Resistance, with Emphasis on Glucocorticoids — A Pilot Study....Pages 286-290 Cytostatic Drug Resistance in Childhood Relapsed Acute Lymphoblastic Leukemia....Pages 291-295 Comparison of Vincristine Pharmacokinetics in Children and Adults....Pages 296-298 Molecular Pathways of Topoisomerase II Regulation and Consequences for Chemotherapy....Pages 299-304 Front Matter....Pages 305-305 Current Treatment and Results of St. Jude Studies for Childhood Acute Lymphoblastic Leukemia....Pages 307-313 Central Nervous System Prophylaxis with High Dose Methotrexate. A Pharmacokinetic and Clinical Study: Results of Protocol FRALLE 89....Pages 314-316 Clinical Relevance of Chromosomal Aberrations in Childhood ALL: Cytogenetic Data of the German Therapy Studies....Pages 317-321 Overview of Dana Farber Cancer Institute-Consortium Childhood Acute Lymphoblastic Leukemia Protocols: 1973–1992....Pages 322-329 Results with Randomized BFM Adopted Studies for ALL Therapy in Childhood in East German Countries....Pages 330-337 Dose Intensity and Prognosis in Acute Lymphocytic Leukemia of Childhood....Pages 338-343 Intensive Chemotherapy for Acute Leukaemias (AL) in Childhood with BFM Protocols. Moscow Experiences 1990–1992. First Successes and Failures....Pages 344-346 Front Matter....Pages 305-305 Improved Prognosis in ALL with Modified BFM Protocols — Preliminary Results from Turkey....Pages 347-351 Long-Term Follow-Up of a Pilot Study of Intermittent Intensive Continuation Therapy (HL-3 Protocol) for Childhood Acute Lymphoblastic Leukemia....Pages 352-358 Successful Central Nervous System Prophylaxis Without Radiotherapy in Childhood Acute Lymphoblastic Leukemia (ALL); Israel National Studies (INS 1984, 1989)....Pages 359-365 Effect of Granulocyte Colony-Stimulating Factor After Intensive Consolidation Therapy on Relapsed Acute Lymphoblastic Leukemia Children....Pages 366-369 R-metHuG-CSF Combined with Chemotherapy for Treatment of Adult ALL — Pilot Study....Pages 370-373 Chemotherapy for Relapsed Childhood Acute Lymphoblastic Leukemia: Results of the BFM Study Group....Pages 374-379 The Proliferative Activity of Blastic Cells in Acid-Phosphatase Positive Childhood Acute Lymphoblastic Leukemia (ALL)....Pages 380-383 Vertebral Compression Fractures in the Course of Acute Lymphoblastic Leukemia in Children....Pages 384-388 Effect of Chemotherapy on Bone Marrow Granulocyte — Macrophage and Stormal Precursors in Children with ALL....Pages 389-392 Influence of Corticosteroids on Coagulation Factors....Pages 393-397 FAB Morphology and Prognosis in Childhood Acute Lymphoblastic Leukemia (ALL)....Pages 398-401 PCR as a Diagnostic Tool in ALL: A Comparison Between Cytogenetic and Polymerase Chain Reaction Analysis in Pediatric Patients with Acute Lymphoblastic Leukemia....Pages 402-404 Prognostic Value of Hypoxanthine-Guanine Phosphoribosyl-Transferase in Childhood Leukemia....Pages 405-409 Front Matter....Pages 411-411 Cytogenetic Findings in Acute Lymphoblastic Leukemia....Pages 413-419 Cancer and Leukemia Group B Studies in Acute Lymphoblastic Leukemia....Pages 420-426 Adult Acute Lymphoblastic Leukemia — Results of the French AALL 87 Protocol with Different Strategies of Postremission Therapy....Pages 427-431 Therapy of Adult Acute Lymphoblastic Leukemia. Preliminary Results of the GIMEMA ALL/0288 Study....Pages 432-436 High-Dose Cytosine Arabinoside in the Treatment of Acute Lymphoblastic Leukaemia....Pages 437-441 Myeloid Surface Antigen Expression in Adult Acute Lymphoblastic Leukemia....Pages 442-446 Efficacy of an Original Cell Kinetics Based Chemotherapy Regimen Using rHU GM-CSF for Induction and Consolidation Treatment of ALL. Preliminary Analysis....Pages 447-451 Front Matter....Pages 411-411 Is Early Response to Chemotherapy a Useful Prognostic Factor in Adult Acute Lymphoblastic Leukemia....Pages 452-454 Analysis of BCR-ABL Rearrangement by PCR in Adult Acute Lymphoblastic Leukemia (ALL): A Report on 28 Cases....Pages 455-457 Front Matter....Pages 459-459 Preliminary Results of AML Therapy in Children Using Targeted Plasma Concentrations of Cytosine Arabinoside and Etoposide....Pages 461-464 Early Intensive Chemotherapy for Children with Acute Myelogenous Leukemia: The Pediatric Oncology Group Experience (1981–1991)....Pages 465-467 Cranial Irradiation is Essential in the Treatment of Childhood Acute Myelogenous Leukemia: Results of Study AML-BFM-87....Pages 468-475 Childrens Cancer Group Transplant Trials for Acute Myeloid Leukemia in Children: A Cross-Study Analysis of CCG-251, CCG-213, CCG-2861, and CCG-2891....Pages 476-485 Six Months of Intensive Chemotherapy for Childhood ANLL: Preliminary Results of the Study ANLL-87 of the Dutch Childhood Leukemia Study Group....Pages 486-489 Multidrug Resistance Reversal Utilizing Mitoxantrone, Etoposide and Continuous Infusion Cyclosporine in Pediatric ANLL....Pages 490-492 Therapy of Acute Myelogenous Leukemia in Childhood — Results of the Multicenter Trial AML II/87 in East Germany....Pages 493-499 Second Remission in Relapsed Childhood Acute Myelogenous Leukemia After Pretreatment with the AML-BFM 83 Protocol....Pages 500-504 Measles Giant Cell Pneumonia in Two Children with Acute Myeloid Leukemia....Pages 505-509 Front Matter....Pages 511-511 Chemotherapy Intensity and Long-Term Outcome in AML....Pages 513-518 Clinical Aspects of Acute Myelogenous Leukemias of the FAB-Types M3 and M4Eo....Pages 519-524 Randomized Study of Intensive Individualized Induction Therapy With or Without Vincristine and of Maintenance/Intensification Therapy in Adult Acute Myeloid Leukemia....Pages 525-529 Recruitment of Leukemia with Combined Granulocyte-Macrophage and Host Stimulatory Factors....Pages 530-540 Clinical Trials Adults with Acute Myelogenous Leukemia: Experience of the Eastern Cooperative Oncology Group....Pages 541-546 Autologous Bone Marrow Transplantation in Acute Leukemia with Edelfosine Purged Marrow....Pages 547-552 Prospective Study on the Clinical Relevance of Residual Disease in Patients with Acute Myeloid Leukemia in Complete Remission....Pages 553-558 Results of AML Treatment....Pages 559-562 AML in the Elderly....Pages 563-566 Front Matter....Pages 511-511 A Multicenter Trial Randomizing Fractionated Aclacinomycin and Cytarabine with or without Etoposide versus “3 + 7” for Primary AML....Pages 567-569 A 12-Year Follow-Up of 101 Patients with Acute Myeloid Leukemia Treated in Two Studies....Pages 570-574 Idarubicin/Cytosine Arabinoside and Mitoxantrone/Etoposide with rhGM-CSF Priming for De Novo Acute Myelogenous Leukemia....Pages 575-577 GM-CSF in a Double-Blind Randomized Placebo-Controlled Trial in Therapy of Adult Patients with De Novo Acute Myeloid Leukemia....Pages 578-581 Significance of Prognostic Factors During an Idarubicin-Containing Regimen in Adult AML....Pages 582-586 Myelodysplastic Remission in De Novo Acute Myeloid Leukemia: Implications for Early Relapse and Putative Monoclonal Remission....Pages 587-594 Cytogenetic Findings Delineating Karyotypic Instability in Erythroleukemia Correlated with Bad Prognosis....Pages 595-601 Presence of inv (16) May Be One of the Only “Favorable” Prognostic Factors in AML: A Report on 16 Cases....Pages 602-605 ALL Transretinoic Acid Followed by Intensive Chemotherapy in Newly Diagnosed Acute Promyelocytic Leukemia: A Pilot Study on 27 Cases....Pages 606-608 Therapy-Related Acute Promyelocytic Leukemia: A Report on 16 Cases....Pages 609-610 Monosymptomatic Relapse of Acute Myeloid Leukemia Confined to the Skin....Pages 611-613 Front Matter....Pages 615-615 Cytogenetics of Acute Leukemia Following MDS....Pages 617-622 Thymidine Kinase Activity in Bone Marrow Cells as Basis for Rational Treatment of Myelodysplastic Syndromes....Pages 623-627 Descriptive Epidemiology of Myelodysplastic Syndromes....Pages 628-632 Myelodysplastic Syndromes: Response to Aggressive Chemotherapy and Prognostic Factors for Treatment Outcome....Pages 633-637 Sequential Administration of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor and Human Erythropoietin for Treatment of Myelodysplastic Syndromes....Pages 638-642 Front Matter....Pages 643-643 Bone Marrow Transplantation for Children with Acute Lymphoblastic Leukemia Failing Conventional Therapy....Pages 645-652 Allogeneic Marrow Transplants in the Acute Leukemias....Pages 653-663 Influence of Growth Suppression of Intestinal Bacteria on the Risk of Acute Graft vs Host Disease After Sibling Marrow Transplantation....Pages 664-672 Autologous Bone Marrow Transplantation in Acute Myelocytic Leukemia in Europe: The Role of Marrow Purging....Pages 673-680 Front Matter....Pages 643-643 IBMTR Analysis of Results of Bone Marrow Transplantation in Acute Leukemia....Pages 681-685 Allogeneic Bone Marrow Transplantation in Patients with AML in First Complete Remission: Prognostic Factors for Survival?....Pages 686-688 Comparison of High-Dose Busulfan and Total Body Irradiation Prior to Allogeneic Bone Marrow Transplantation....Pages 689-693 Graft Rejection After Allogeneic Bone Marrow Transplantation: The Impact of T Cells, Graft-Versus-Host Reaction and Marrow Cell Number....Pages 694-699 Continuous Intravenous Pentoxifylline in Bone Marrow Transplant Recipients: First Results of a Pilot Study....Pages 700-704 Autologous Transplantation with Mafosfamide-Purged Bone Marrow for Acute Myelogenous Leukemia in First and Second Complete Remission....Pages 705-708 Graft-Versus Leukemia Activity in Experimental Bone Marrow Transplantation: The Impact of Natural Killer Cells and Graft-Versus-Host Disease....Pages 709-716 Fractionated Total Body Irradiation or Busulfan in Combination with Etoposide and Cyclophosphamide as Conditioning Regimen for Bone Marrow Transplantation in Acute Leukemias in Children....Pages 717-720 Autologous and Allogeneic Bone Marrow Transplantation After Identical High-Dose Chemo-Radiotherapy in Children with Relapsed ALL....Pages 721-723 Bone Marrow Transplantation from an Unrelated Donor: Experiences in Children....Pages 724-726 Successful Adoptive Immunotransfers in a Boy with Relapse of T-ALL After Bone Marrow Transplantation from an Unrelated Donor....Pages 727-729 Fluoroquinolones for Infection Prevention After Bone Marrow Transplantation....Pages 730-731 Front Matter....Pages 733-733 New Drugs for the Prevention and Treatment of Pneumocystis carinii Pneumonia....Pages 735-737 Prevention of Bacterial Infections in Patients with Profound Granulocytopenia: Experience of the Institute Jules Bordet....Pages 738-743 Interventional Antimicrobial Strategy for the Management of Infections in Neutropenic Patients with Hematologic Malignancies: Results of a Multi-Center Randomized Comparison of Antimicrobial Regiments....Pages 744-747 Treatment of Fungal Infections....Pages 748-757 Cancer and Leukemia Group B (CALGB) Studies with Hematopoietic Growth Factors in Patients with Acute Myeloid Leukemia....Pages 758-761 Inhalation of Amphotericin B for Prophylaxis of Invasive Fungal Infections During Intensive Leukemia Therapy....Pages 762-764 Inhalation of Amphotericin B for Prophylaxis of Invasive Fungal Infections During Intensive Leukemia Therapy....Pages 765-767 The Frequency of Bacterial and Fungal Infections in Acute Leukemia Types According to F AB Classification....Pages 768-771 Once Daily Dosing of Netilmicin in the Empirical Treatment of Fever in the Neutropenic Patient....Pages 772-773 Interventional Treatment of Unexplained Fever (FUO) and Documented Infections in Neutropenic Patients with Hematological Malignancies: Fluconazole vs Amphotericin B/5-Flucytosine....Pages 774-777 Invasive Aspergillosis During Chemotherapy in Children....Pages 778-781 Liposomal Amphotericin B (AMBISOME) in Patients with Severe Neutropenia and Antibiotic Resistant Fever....Pages 782-784 Efficacy of Liposomal Amphotericin B (AmBisome) in Neutropenic Patients with Fungal Infections....Pages 785-786 Differential Cell Count and Lymphocyte Subsets of Bronchoalveolar Lavage in Patients with Severe Granulocytopenia....Pages 787-791 Cytomegalovirus Infection in Children with Blood Malignancies and Aplastic Anemias....Pages 792-794 Emerging Bacterial Pathogens in Patients with Acute Leukemia: Viridans Streptococci and Non-Fermentative Gram-Negative Bacilli....Pages 795-798 Back Matter....Pages 799-803 This 4th of a series of volumes again provides the state of the art in characterization and treatment of acute leukemias. The therapeutic progress is reflected by updates from major prospective clinical studies. The role of chemotherapy modi- fications and of bone marrow transplantation is elucidated and compared. Among prognostic factors the Philadelphia chromosome and bcr-abl gene rearrangement emerged as the most powerful risk factor in acute lymphoblastic leukemia. Molecularas well as immunologic leukemic cell markers open ways to monitor residual leukemia in clinical remission. Differentiation induction by retinoids represent a novel therapeutic principal as does the modulatioon of chemothera- py by hematopoietic growth factors. The new antileukemic ap- proaches are supported by more effective anti-infectious strategies. Data from clinical and laboratory research are presented in tables and illustrations. Up to date comprehensive overview of the large field of acu- te leukemia research and management