Acute Leukemias V: Experimental Approaches and Management of Refractory Disease

ISBN-13: 9783642789090 / Angielski / Miękka / 2012 / 613 str.

Wolfgang Hiddemann; Thomas Buchner; Bernhard Wormann

Opis

150 years after the first description of the clinical picture of "white blood" and the introduction of the term "leukemia" by R. Virchow it appears, that the leukemias, and the acute leukemias in particular, serve as an impressive example for the major improvements that have been achieved in the treatment but also in the understand ing of the biology of malignant dis orders. The international symposia "Acute Leukemia" which are held at Munster since 1986 have developed into an interna tional forum to review the current progress and the future perspectives of leukemia research and therapy at a high scientific and clinicallevel. Since the possibility for active participation in these symposia is somewhat restricted we are glad to have the opportunity to extend the information that was presented at the symposium "Acute Leukemias V - Experimental Approaches and Management of Refractory Disease" which was held from February 27 to March 2, 1994 to a broader audience of basic scientists and clinicians. This meeting was especiaIly designed to discuss experimen tal approaches and the management of refractory disease which allows to evaluate new experimental therapies on the basis of preclinical studies."

Spis treści

Leukemia Cell Biology.- Cell Differentiation and Programmed Cell Death: A New Approach to Leukemia Therapy.- CD34 and CD38 Expression on Blasts in Myelodysplastic Syndromes and Secondary AML.- Heterogeneity of HRX-FEL Fusion Transcripts in Adult and Pediatric t(4;11) ALL.- Pharmacokinetics — Clinical Implications.- Fludarabine and Ara-C Combination for Treatment of Adult Acute Myelogenous Leukemia: Pharmacokinetic and Pharmacodynamic Effects.- Pharmacokinetics of Ara-CMP-Stearate (YNK01) — Phase I Study of the Oral Ara-C Derivative.- Differential Effect of GM-CSF on the Intracellular Ara-C Metabolism in Normal Bone Marrow Mononuclear Cells and Acute Myeloid Leukemia (AML) Blasts.- Intracellular Retention of Cytosine-Arabinoside-Triphosphate in Leukemic Blast Cells from Children.- The Pharmacokinetics of Epipodophyllotoxins — Clinical Relevance.- Targeted Drug Therapy in Childhood Acute Lymphoblastic Leukemia.- Asparagine Levels in Children on E. Coli- and Erwinia-Asparaginase Therapy.- Chemo-Resistance.- Pharmacologic Modulation of Multidrug Resistance in Acute Leukemia: Results and Challenges.- Kinetic Resistance, Regrowth Resistance, and Multidrug Resistance in the Treatment of Acute Myelogenous Leukemia (AML).- Topoisomerases — from Basic Research to Clinical Implications.- Mechanisms of Acquired ARA-C and DAC-Resistance in Acute Myeloid Leukemia (AML): Development of a Model for the Study of Mutational Loss of Deoxycytidine Kinase (DCK) Activity.- Expression of P-Glycoprotein in Children and Adults with Leukemia — Correlation with Clinical Outcome.- Multidrug Resistance in Acute Myelogenous Leukemia: Relevance to Clinical and Laboratory Data.- Mitoxantrone/Cytarabine with or without Quinine as a Potential MDR-Reserving Agent for the Treatment of Acute Leukemias.- In Vitro Modulation of Multidrug Resistance by BIBW22BS in Blasts of De Novo or Relapsed or Persistent AML.- In Vitro Drug Resistance Profiles in Childhood Acute Lymphoblastic Leukemia.- Growth Factors — Modulation.- The Expression and Regulation of G-CSF and GM-CSF.- In Situ Nick Translation as a Measure of Cell Death. Application to the Study of Growth Factors and Drug Sensitivity.- Molecular Mechanisms of Ara-C Signalling: Synergy and Antagonism with Interleukin-3.- Hematopoietic Recovery and Priming — Therapeutic Effects of GM-CSF in the Treatment of AML.- Improved Antileukemic Activity of the Combination of Ara-C with GM-CSF and IL-3 Fusion Protein (PIXY321).- A Double-blind Controlled Study of G-CSF Started Two Days Before Induction Chemotheraphy in Refractory Acute Myeloid Leukemia.- Effects of Growth Factors In Vitro on Acute Lymphoblastic Leukemia Cells.- The Experience of Polish Children’s Leukemia Lymphoma Study Group on G-CSF and GM-CSF Interventional Use in Neutropenia Associated with Chemotheraphy of Childhood Acute Lymphoblastic Leukemia (ALL).- Induction Therapy with Idarubicin, Ara-C, and VP-16 Followed by G-CSF and Maintenance Immunotherapy with Interleukin-2 for High-Risk AML.- Incidence of Infections in Adult Patients (> 55 Years) with Acute Myeloid Leukemia Treated with Yeast-Derived GM-CSF (Sargramostim): Results of a Double-Blind Prospective Study by the Eastern Cooperative Oncology Group.- Chemotheraphy in AML.- New Approaches in the Treatment of AML and MDS.- S-HAM Salvage Therapy of Relapsed and Refractory AML Followed by Interleukin 2 Postremission Therapy.- Mitoxantrone-Etoposide or HD-ARA-C/Mitoxantrone for Remission Induction in Children with First Relapse of AML.- Sequential Mitoxantrone, Ara-C and VP-16 (s-MAV) Followed by Immuno-Maintenance-Therapy with Interleukin-2 (IL-2) in the Treatment of Refractory and Relapsed Acute Myelogenous Leukemia.- Mitoxantrone, Etoposide and Cyclosporine A Therapy for Relapsed and Refractory Acute Myelogenous Leukemia, A Pediatric Oncology Group Phase II Trial.- Sequential Chemotherapy with Mitoxantrone, Etoposide and Cytarabine for Previously Treated Acute Myeloid Leukemia. EMA 886 Regimen.- Treatment of Childhood Acute Nonlymphoblastic Leukemia — Final Results of the Austrian-Hungarian Study AML-IGCI-84.- TAD Double Induction, HDAra C Consolidation, Rotation Maintenance in ANLL: the Results and Prophylaxis of Hepatitis and Fungal Infection.- Chemotherapy in ALL.- Salvage Therapy of Childhood ALL: Prognosis of Marrow Relapse After Intensive Front-line Therapy.- Salvage Therapy of Adult ALL.- Protocol RACOP in the Treatment of Resistant and Relapsed ALL.- Treatment of Philadelphia Chromosome Positive ALL with Interferon Alpha.- Six Years’ Experience with Treatment of Recurrent Childhood Lymphoblastic Leukemia. Report of the Polish Children’s Leukemia/Lymphoma Study Group.- Interim Results of a Phase II Study with Idarubicin in Relapsed Childhood Acute Lymphoblastic Leukemia.- Leukemia-Lymphoma in Children with Primary Nodal Peripheral and Mediastinal Involvement.- Immunotherapy of Acute Leukemias.- Induction of Immunity Against Leukemia.- IL2 in Acute Leukemia.- Is There a Role for Interleukin-2 Gene Transfer in the Management of Acute Leukemia?.- Use of Roquinimex in the Myeloid Leukemias.- The Inhibition of Lymphokine Activated Killer Cell Activation Mediated by AML Culture Supernatants Might Be Due to Transforming Growth Factor Beta 1.- Natural Killer Cell Alloreactivity Against Acute Leukemia Blasts: The Level of Activity Depends on the Individual Target-Effector Pair.- Cellular Immunotherapy of Acute Leukemias After High Dose Chemotherapy with Cytarabin (ARA-C) and Cyclophosphamide (CY) in a Murine Model.- Interleukin-2 Bolus Infusion as Consolidation Therapy in 2nd Remission of Acute Myelocytic Leukemia.- Interleukin-2 Postremission Therapy in Acute Myeloid Leukemia (AML): In Vitro and In Vivo Effects of a Five Day Continuous Infusion of IL-2 on Phenotype and Function of Peripheral Lymphocytes.- Comparison of Immunological and Molecular Markers When Using Interleukin-2 (IL-2) Alone or in Combination with ?-Interferon (IFN-?) in the Maintenance Therapy of Acute Myeloid Leukemia (AML).- Immunological Response to IL-2 AND ?-IFN-Treatment After Autologous BMT in Patients with BCR-ABL-positive ALL.- Bone Marrow Transplantation.- Conditioning Regimens for Bone Marrow and Peripheral Blood Stem Cell Transplantation.- Influence of Different Conditioning Regimens on Stroma Precursors.- Autologous Bone Marrow Transplantation in Relapsing Acute Leukemias.- Autologous Vs. Unrelated Donor Bone Marrow Transplantation for Acute Lymphoblastic Leukemia Considerations and Logistics.- Comparison Between Allogeneic and Autologous Bone Marrow Transplantation for Childhood Acute Lymphoblastic Leukemia in Second Remission.- Comparison of Allogeneic and Autologous Bone Marrow Transplantation for Treatment of Childhood Acute Myeloblastic Leukemia (AML) in First Complete Remission.- Long-Term Results in Adult AML: Comparison of Postremission Chemotherapy vs. Autologous BMT vs. Allogeneic BMT.- Allogeneic BMT in Patients with AML Influence of the Prior Response to Induction Chemotherapy on Outcome After BMT.- Donor Leukocyte Infusions (DLI) in the Treatment of AML Patients Relapsed After Allogeneic Bone Marrow Transplantation.- Recombinant Human Erythropoietin After Bone Marrow Transplantation — A Placebo Controlled Trial.- Novel Therapeutic Approaches.- Combination of rhSCF + rhG-SCF, But Not rhG-CSF Alone Potentiate the Moblization of Hematopoietic Stem Cells with Increased Repopulating Ability into Peripheral Blood of Mice.- High-dose Therapy and Autografting with Mobilized Peripheral Blood Progenitor Cells in Patients with Malignant Lymphoma.- Cord Blood Banking for Hematopoietic Stem Cell Transplantation.- Molecular Basis for Retinoic Acid Effects in Acute Promyelocytic Leukemia.- Acute Promyelocytic Leukemia: Advantage of A-Trans Retinoic Acid (ATRA) over Conventional Chemotherapy.- Studies of 2-Chlorodeoxyadenosine (Cladribine) at St. Jude Children’s Research Hospital.- The Role of 2-Chlorodeoxyadenosine (2-CDA) in the Treatment of Lymphoid Malignancies: Preliminary Observations.- Cytarabine Ocfosfate, a New Oral Ara-C Analogue, in the Treatment of Acute Leukemia and Myelodysplastic Syndromes.- Tumor Immunotherapy by IL-2 and IL-2 Gene Transfected Cells.- Myeloid Differentiation Mediated Through New Potent Retinoids and Vitamin D3 Analogs.- Residual Disease.- Functional Assays for Human AML Cells by Transplantation into SCID Mice.- Cytogenetics and Clonal Evolution in Childhood Acute Lymphoblastic Leukemia (ALL).- Molecular Biology of Acute Lymphoblastic Leukemia: Implications for Detection of Minimal Residual Disease.- Detection of AML1/ETO-Rearrangements in Acute Myeloid Leukemia with a Translocation t(8;21).- Mastocytosis in AML-M2 with t(8;21) — a New Characteristic Association.- Acute Myeloid Leukemia with Translocation (8;21). Cytomorphology, Dysplasia and Prognostic Factors in 41 Cases.- Simultaneous Occurrence of t(8;21) and del(5q) in Myeloid Neoplasms.- Detection of MLL/AF4 Recombination by PCR Technique.- Detection of Different 11q23 Chromosomal Abnormalities by Multiplex-PCR Using Automatic Fluorescence-Based DNA-Fragment Analysis.- Designing Probe Sets for the Detection of Chromosome Abnormalities in Acute Myeloid Leukemia Using Fluorescence In Situ Hybridization.- The Amplification of the Wilms Tumor Gene (wt-1) mRNA Using the Polymerase Chain Reaction Technique (PCR) May Enable Sensitive Detection of Small Blast Populations in AML.- Distribution of Cells with a “Stem Cell Like” Immunophenotype in Acute Leukemia.- Expression of Human Endogenous Retroviral (HERV) Sequences in Hematological Disorders.- DNA-Analysis by Flow-Cytometry of up to Nine Year Old Methanol/Acetic Acid Fixed Samples of Childhood Acute Lymphoblastic Leukemia (ALL).- Biological Entities in Acute Myelogenous Leukemia According to Morphological, Cytogenetic and Immunological Criteria: Data of Study AML-BFM-87.- Expression of CD7 and CD15 on Leukemic Blasts Are Prognostic Parameters in Patients with Acute Myelocytic Leukemia — Irrelevance of CD34.- IL-2 Receptor (IL-2R) Alpha, Beta, and Gamma Chains Expressed on Blasts of Acute Mylelocytic Leukemia May Not Be Functional.- Stromal Function in Long Term Bone Marrow Culture of Patients with Acute Myeloid Leukemia.- Fluorescence In Situ Hybridization for the Diagnosis and Follow-up of BCR-ABL Positive ALL.- Supportive Care.- Incidence and Severity of Amphotericin B-induced Acute Toxicity in Leukemic Patients After Treatment with Three Different Formulations (Amphotericin B, AmBisome and Amphotericin B/Intralipid) — A Pilot Study.- Pulmonary Infiltrates in Patients with Hematologic Malignancies: Clinical Usefulness of Non-bioptic Bronchoscopic Techniques.- Fludarabine in Chronic Lymphocytic Leukemia and Maligant Lymphomas.- New Aspects in the Treatment of Chronic Lymphocytic Leukemia.- The Use of Fludarabine in Chronic Lymphocytic Leukemia and Malignant Lymphomas.- Response to Fludarabine in Patients with Low Grade Lymphoma.- Fludarabine in Combination with Mitoxantrone and Dexamethasone in Relapsed and Refractory Low-Grade Non-Hodgkin’s Lymphoma.- Novantrone — Current Status and Future Perspectives.- New Anthracyclines — A Comparative Analysis of Efficacy and Toxicity.- Hematologic and Therapeutic Effects of High-Dose AraC/Mitoxantrone (HAM) in the Induction Treatment of Patients with Newly Diagnosed AML. A Trial by AML Cooperative Group.- Comparison of Front-Line Chemotherapy for Intermediate Grade and Follicular Non-Hodgkin’s Lymphoma Using the CAP-BOP Regimens.- Prednimustine and Mitoxantrone in the Treatment of Low-Grade Non-Hodgkin Lymphomas.- Mono- Versus Combination-Chemotherapy in Metastatic Breast Cancer.

Blurb

This volume, the fifth in a series on acute leukemias, focuses particularly on recent basic research results and novel therapeutic approaches to the disease. Aspects of leukemia cell biology, including differentiation, the mechanisms of drug resistance, the pharmacology of cytostatic agents and the results of clinical trials in relapsed and refractory disease are covered by outstanding international experts in the respective fields. Future developments including new agents and new treatment options such as unrelated bone marrow transplantation, immunotargeting and gene therapy complete a state-of-the-art summery of current knowledge in experimental leukemia therapy.