Acute Leukemias VII: Experimental Approaches and Novel Therapies

Front Matter....Pages I-XXXVII
Front Matter....Pages 1-1
Alterations in DNA Repair: Implications for Leukemia Cell Biology....Pages 3-12
Functional Characterization of Leukemic Stem Cells in Acute Myeloid Leukemia....Pages 13-18
Involvement of CD34+ Stem Cells in Malignant Transformation in AML and MDS — Genetic Analysis of Sorted Subpopulations by Classical and Molecular Cytogenetics....Pages 19-28
Mutations of Mitochondrial DNA as an Early Event in the Pathogenesis of Myelodysplastic Syndromes....Pages 29-41
Pilot Study of Pentoxifylline and Ciprofloxacin with or without Dexamenthasone Produces Encouraging Results in Myelodysplastic Syndromes....Pages 42-51
Expression of Differentiation Antigens on Blast Cells of Acute Myelogenous Leukemia (AML, M0–M6)....Pages 52-58
Cytoplasmatic Expression of CD34 in Acute Leukemia....Pages 59-61
Flow Cytometry of Leukocyte Alkaline Phosphatase in Human Hematopoietic Cells....Pages 62-67
Biologic Determinants for AML Therapy....Pages 68-72
Evaluation Of NOD-SCID-Mice for a Human B-Cell Precursor ALL Xenograft Model....Pages 73-77
Flow Cytometric Analysis of Immature Cell Populations in B-Cell Precursor ALL....Pages 78-81
Immunophenotypical Subtype of Childhood T-All with Favourable Outcome in the COALL 1985–1992 Study Group....Pages 82-89
Acute Leukemias with Hybrid Features in Children and Adolescents from the Kiev Region (Ukraine)....Pages 90-94
CD95(Fas/APO-1) Antigen Expression on the Cells of Myelodysplastic Syndromes, Acute Myelogenous Leukemia, and Chronic Myelogenous Leukemia Patients....Pages 95-101
The Premyelodysplastic State and the Secondary Hematologic Disorders....Pages 102-107
Physiological Events during Ara-C Toxicity Mapped Using Multiparametric Flow Cytometry....Pages 108-121
CD95-Mediated Apoptosis in Acute Myeloid Leukemia (AML): Dependence on Maturational Stage and Growth Characteristics in Vitro....Pages 122-130
Structural Properties of the Cell Membrane of Apoptosis-Induced Cells and Leucemic Blast Cells Studied by Electrospinresonance-Spectroscopy....Pages 131-136
Simultaneous Detection of Leukemia Blast Cells on PB/BM — Smears Combining May-Gruenwald Giemsa- and APAAP Staining....Pages 137-145
Anomalistic Signaling as a Possible Biochemical Explanation for Discordant Maturation in Chronic Myelogenous Leukemia (CML)....Pages 146-181
Front Matter....Pages 1-1
Transformation of Myeloid Cells by the BCR/ABL Oncogene....Pages 182-189
New Isoforms of the ZFM1 Gene: a Growing Family of Signal Transduction and Activator of RNA (STAR) Proteins....Pages 190-198
Expression of Tie Receptor Tyrosine Kinase in Leukemia Cell Lines....Pages 199-205
Acute Erythroblastic Leukemia is a Rare, but Distinct Subtytpe of Acute Myeloid Leukemia....Pages 206-210
Plasma Cell Leukemia in a 7-month-old Infant....Pages 211-213
Myelodysplastic Syndromes in Children: Clinical and Morphological Analysis....Pages 214-216
Front Matter....Pages 217-217
Molecular Screening of Acute Myeloid Leukemia Using Interphase Cytogenetics....Pages 219-224
Routinely Prepared Cells for Cytogenetic Analysis Stored at −20 °C for Several Years can be Used for RT-PCR-Based Detection of Chromosomal Aberrations in Leukemias....Pages 225-228
RT-PCR-Based Detection of TEL/AML1 Fusion Transcript in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia — a Czech Childhood Leukemia Working Group Experience....Pages 229-233
Occurrence of TEL-AML1 Fusion Resulting from (12;21) Translocation in Human Early B-Lineage Leukemia Cell Lines....Pages 234-241
Frequent Loss of Heterozygosity on Chromosomes 6q, 9p, 11q or 12p in Childhood Acute Lymphoblastic Leukemia....Pages 242-247
Deletions of Human Chromosome Region 6q23-24 in B-Lineage Neoplasias....Pages 248-252
Excessive Differentiation of Myeloid Cells in AML-M2 with Translocation 8;21....Pages 253-258
The Prognostic Impact of Trisomy 8 in Acute Myeloid Leukemia: Do Accompanying Aberrations Influence Prognosis?....Pages 259-264
G-CSF Increases the Number of Trisomy 8 Metaphases in Vitro in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome....Pages 265-268
The Karyotype in MDS — Cytogenetic Profile, Clinical Correlations and Prognostic Implications in 362 Patients with MDS....Pages 269-277
Front Matter....Pages 279-279
Vitamin D 3 and Retinoid-Mediated Inhibition of Leukemic Cells....Pages 281-301
Growth Factors in the Treatment of Acute Lymphoblastic Leukemia....Pages 302-306
Control of Leukemia Proliferation in vivo in Patients: In vivo Cytokine Production....Pages 307-316
Hematopoietic Growth Factors: Supportive and Priming Effects in AML....Pages 317-320
Front Matter....Pages 279-279
The Role of Growth Factors in the Treatment of AML....Pages 321-326
Growth Factors in Elderly Patients with Acute Myeloid Leukemia....Pages 327-332
The Role of Growth Factors in Myelodysplastic Syndromes: Biological and Clinical Factors....Pages 333-342
Clinical Trials of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor (PEG-rHuMGDF)....Pages 343-346
Increased Numbers of Progenitor Cells in the Apheresis Product of Patients Randomised to Receive Increasing Doses of Stem Cell Factor (r-metHuSCF) Administered in Combination with Chemotherapy and a Standard Dose of Filgrastim (r-metHuG-CSF)....Pages 347-355
The Influence of Surface Receptors for G + GM-CSF, IL-3 and SCF and S-Phase Recruitment of AML Cells on Response to First Phase Chemotherapy....Pages 356-362
Shc Overexpression Induces Selective Hypersensitivity to GM-CSF and Prevents Apoptosis of the GM-CSF-Dependent Acute Myelogenous Leukemia Cell Line GF-D8....Pages 363-368
ICAM-1 Levels Correlations with Cytokine (IL-1, IL-6 and TNF) Production During the Course of Acute Lymphoblastic Leukemia (ALL) in Children....Pages 369-374
High Serum IGFBP-2 in Acute Lymphoblastic Leukemia may be an Indication for Increased Risk of Relapse....Pages 375-378
Thrombopoietin Supports the Continuous Growth of Cytokine-Dependent Human Leukemia Cell Lines....Pages 379-386
Generation of Active Oxygen Forms by Neutrophils and Granulocytopoiesis in Patients with Acute Lymphoblastic Leukemia under Therapy with Use of G-CSF Granocyte....Pages 387-393
Front Matter....Pages 395-395
Lineage-Tropism of Murine Leukemia Virus Enhancer Activity within the Hematopoietic System....Pages 397-404
Retrovirus and Adenovirus-Mediated Interferon Gene Transfer into Hematopoietic Stem Cells (CD 34+) of Normal and Chronic Myelogenous Leukemia....Pages 405-412
AML in the Elderly: a Biologically Distinct Disease in which MDR1 Expression and Unfavorable Cytogenetics Contribute to Poor Clinical Response. Studies of the Southwest Oncology Group....Pages 413-421
Pharmacological Modulators and Alternate Mechanisms of Multidrug Resistance....Pages 422-430
Some Reflections on P-Glycoprotein Expression in Acute Leukemia....Pages 431-443
In Acute Myeloid Leukemia only the Coexpression of at Least Two Proteins Including P-Glycoprotein, the Multidrug Resistance-Related Protein MRP, bcl-2, Mutant p53 and Heat-Shock Protein 27 is Predictive for the Response to Induction Chemotherapy....Pages 444-453
Human P-Glycoprotein/Mdr1-Gene Product: Surprising Potential for Nuclear Localization and Coupling to Intracellular Growth Factor Signalling....Pages 454-455
Treatment of Poor Prognosis Acute Myelogenous Leukemia with PSC-833 and Mitoxantrone, Etoposide, Cytarabine....Pages 456-460
Approaches to Overcome Multidrug Resistance: PSC and CdA/ara-C Combination Chemotherapy....Pages 461-468
Front Matter....Pages 395-395
Zidovudine Induces Resistance to Antineoplastic Agents and Alterations in Apoptosis in T-Cell Lymphoma Cells....Pages 469-474
Idarubicin Activity Against Multidrug-Resistant (mdr-1+) Cells is Increased by Cyclosporin A....Pages 475-482
Protection of Marrow from Methotrexate Toxicity by Gene Transfer of Mutant Forms of Dihydrofolate Reductase into Hematopoietic Progenitor Cells....Pages 483-490
In Vitro Drug Resistance in Childhood Acute Myeloid Leukemia: a Preliminary Analysis....Pages 491-495
Correlation of in Vitro Drug Sensitivity with Clinical Outcome in Adult AML....Pages 496-502
Drug Resistance Testing of Acute Myelogenous Leukemia in Adults — Initial Results with the MTT Assay....Pages 503-508
Predictive Value of Pretherapeutic In-Vitro Chemosensitivity Testing in Adult AML....Pages 509-514
Functional Studies of Daunorubicin Transport in Human Leukemic Cells....Pages 515-520
Front Matter....Pages 521-521
Pharmacokinetics and Pharmacodynamics of Asparaginase....Pages 523-529
Asparagine Synthetase in Pediatric Acute Leukemias: AML-M5 Subtype Shows Lowest Activity....Pages 530-535
Pharmacokinetic Basis for an Oral Chemotherapy with Idarubicin and Etoposide: Dose-Dependent Biological Effects of Topoisomerase-II-Inhibitors....Pages 536-543
Involvement of ICE-Like Proteases in Gemcitabine-Induced Programmed Cell Death....Pages 544-548
Effect of Combined Treatment with 4-Hydroperoxycyclophosphamide and Fludarabine on Cytotoxicity and Repair of Damaged DNA....Pages 549-555
Enhanced Effects of Adriamycin by Combination with a New Ribonucleotide Reductase Inhibitor,Trimidox, in Murine Leukemia....Pages 556-561
Pharmacological Aspects of the Oral Application of Etoposide....Pages 562-564
Pharmacokinetics and Metabolism of Low-Dose ATRA in Children — First Observations....Pages 565-569
In Vitro Monitoring of Asparaginase: Unphysiological Alteration of the Culture Medium....Pages 570-574
Front Matter....Pages 575-575
Modulation of Ara-C Metabolism to Improve AML Response....Pages 577-583
Response of AML Blasts to Ara-C: Role of BCL-2 in the Regulation of Drug Sensitivity....Pages 584-595
AraC Metabolism in Fresh Leukemic Blasts/ Normal Bone Marrow/ Hematopoetic Stem Cells and its Impact on the Lipid Composition of Leukemic Cells (HL60)....Pages 596-602
Front Matter....Pages 575-575
Interaction of 1-β-D-Arabinofuranosylcytosine with Lipid Metabolism....Pages 603-613
Cellular Metabolism and T-ALL Specificity of Arabinosylguanine: a Review....Pages 614-619
Modulation of Ara-C Cytotoxicity by Coadministration with Antisignalling Drugs in HL60 and Ara-C-Resistant HL60/Ara-C Cells....Pages 620-627
Cytotoxic Activity and Pharmacology of an Ara-CMP Prodrug in T-leukemic Sublines Resistant to Ara-C....Pages 628-632
Retinoids Modulate Ara-CTP Pharmacology in the HL-60 Acute Leukemia Cell line....Pages 633-639
Induction of Apoptosis in Vitro by ARA-C, VP-16, MITOX, DNR, IDA and FLU in Myeloid Leukemic Cells....Pages 640-644
Comparison of Hydroxyurea, Fludarabine and Cladribine in Modulating Ara-C Pharmacology in the Ara-C sensitive and resistant HL-60 and HL-60/Ara-C Cell Lines....Pages 645-650
Primary Resistance to Ara-C in AML Progenitor Cells and its Modulation by Cytokines....Pages 651-654
Gemcitabine-Mediated Enhancement of Cellular Cytarabine-5′-Triphosphate (ara-CTP) Accumulation....Pages 655-660
Front Matter....Pages 661-661
Experimental Basis for Immunotherapy of Metastases....Pages 663-668
Gene Marking to Establish the Biology of Minimal Residual Disease and Relapse....Pages 669-678
Adoptive Immunotherapy in the Treatment of Post-Transplant Relapse and Epstein-Barr Virus Lymphoproliferative Disorders....Pages 679-684
Induction of Graft-versus-Leukemia-Activity after Peripheral Blood Progenitor Cell Transplantation (PBPCT)....Pages 685-692
Induction and Post-Remission Therapy in Acute Myeloid Leukemia: Experience of the Eastern Cooperative Oncology Group (ECOG)....Pages 693-699
Cellular Immunotherapy of Cancer: Adoptive Transfer of Monocyte-Derived Tumorcytotoxic Macrophages....Pages 700-708
GM-CSF Stimulation of Immune Response in Minimal Residual Cancer....Pages 709-715
T-Cell-Mediated Immunity against B-Cell Malignancies: Preclinical Results and Translation into a Novel Immunotherapeutic Approach for B-Cell Malignancies....Pages 716-731
Front Matter....Pages 733-733
Treatment of Children with Relapsed Acute Lymphoblastic Leukemia Studies of the BFM Study Group....Pages 735-740
Experience with BFM 1990 Protocol Treatment of Recurrent Childhood Lymphoblastic Leukemia. Report of the Polish Children’s Leukemia/Lymphoma Study Group....Pages 741-749
Modified New York Regimen for Children with High Risk Acute Lymphoblastic Leucemia (HR-ALL). Preliminary Results....Pages 750-752
Front Matter....Pages 753-753
Treatment of High-Risk Acute Lymphoblastic Leukemia. Preliminary Results of the Protocol PETHEMA ALL-93....Pages 755-765
Idarubicin and Ifosfamide in the Treatment of Refractory and Relapsed Acute Lymphoblastic Leukemia....Pages 766-770
Treatment of Ph+ and t(4;11)+ Acute Lymphoblastic Leukemia in Adults....Pages 771-778
Philadelphia (Ph)-Chromosome-Negative Peripheral Blood Stem Cells can be Mobilized in the Early Phase of Recovery after a Myelosuppressive Chemotherapy in Ph-Chromosome-Positive Acute Lymphoblastic Leukemia....Pages 779-782
Prolonged Remission in Adult B-ALL (L3) and Advanced Burkitt’s Lymphoma Using Acute Leukaemia Regimens: Study of 34 Patients....Pages 783-789
Autologous Bone Marrow Transplantation in Adult Lymphoblastic Leukaemia — Single Centre Experience....Pages 790-796
Cranial Computed Tomographic Scans at Diagnosis in Children with Leukemia....Pages 797-800
Front Matter....Pages 801-801
Autologous Bone Marrow Transplantation in First Complete Remission as Intensification Therapy in Children with High Risk AML — Results of the Pediatric Cooperative AML Trial 1987–1992 in East Germany....Pages 803-809
Risk Factors for Survival in Children with Refractory AML Treated According to AML Relapse Strategies....Pages 810-817
Front Matter....Pages 819-819
Intensified Therapy for AML:The Role of the HAM Combination....Pages 821-823
Recent Studies in AML, RAEB-t, and RAEB at M.D. Anderson Hospital....Pages 824-827
FLAG-Ida, an Effective Regimen for High Risk AML....Pages 828-833
Chemotherapy with Idarubicin, Ara-C,VP-16, Amsacrine, Followed by G-CSF and Maintenance Immunotherapy with Interleukin-2 for Patients with High-Risk Acute Myeloid leukemia: a 3-Years Follow-Up....Pages 834-837
Time Sequential Therapy (TAD-HAM) for Secondary AML with and without G-CSF Priming and Support — a Randomized Study....Pages 838-840
Oral Chemotherapy for Acute Myeloid Leukaemia....Pages 841-848
Oral Idarubicin in the Treatment of AML....Pages 849-854
Acute Myeloid Leukemia in Patients Aged Over 75 Years: Clinico-Hematological Characteristics and Treatment Results....Pages 855-861
Improved Results of AML Treatment in Adults during a 12-Year Period. A Population-Based Study....Pages 862-866
Stratification of Postremission Therapy in Adult Acute Myeloid Leukemia According to the Karyotype — Preliminary Results of the Multicenter Treatment Trial AML HD93....Pages 867-876
Continuous Infusion of Mitoxantrone Combined with High Dose Cytarabine (c-HAM) in de Novo AML....Pages 877-880
Front Matter....Pages 819-819
All-Trans Retinoic Acid (ATRA) Combined with Double Induction Strategy in Acute Promyelocytic Leukemia (APL). Preliminary Results....Pages 881-885
The Effect of ATRA (Roche) on Clinical and Laboratory Parameters in 36 APL Patients — Polish Multicenter Retrospective Analysis....Pages 886-889
Abundance of Auer Bodies and Bilobed Nuclei of Leukemic Cells may be Related to Longer Disease Free Survival of Patients with Acute Promyelocytic Leukemia (M3)....Pages 890-894
The Influence of Dysplastic Hematopoiesis on the Outcome in Patients with de Novo AML....Pages 895-900
Trial to Extract Prognostic Factors Prior to the Start of Induction Chemotherapy for Adult AML....Pages 901-905
Stem Cell Transplants in Acute Myeloid Leukaemia (AML)....Pages 906-910
Blood Stem Cell Transplantation in Acute Myeloid Leukemia....Pages 911-914
Peripheral Blood Stem Cell Transplantation During Postremission Treatment of de Novo Acute Myelogenous Leukemia....Pages 915-921
Myeloablative Chemotherapy and Peripheral Blood Stem Cell Transplantation vs. Consolidation Therapy of Acute Myelogenous Leukemia in First Remission....Pages 922-931
Treatment of Relapsed and Refractory Acute Myeloid Leukemias — Strategies of the German AML Cooperative Group (AMLCG)....Pages 932-935
Intermediate Dose Cytarabine and Idarubicin for Salvage Therapy of Acute Myeloid Leukemia....Pages 936-942
Superiority of High-Dose over Intermediate-Dose Cytosine Arabinoside (AraC) in the Treatment of Patients with High-Risk Acute Myeloid Leukemia (AML)....Pages 943-953
Granulocyte Colony-Stimulating Factor Improves the Antileukemic Efficacy of the Sequential High-Dose Cytosine Arabinoside and Mitoxantrone Regimen (S-HAM) in Patients Younger than 60 Years with High-Risk Acute Myeloid Leukemia....Pages 954-962
Therapy of Advanced MDS, AML Evolving from MDS, or Secondary AML with Idarubicin Ara-C, VP-16, Followed by G-CSF-Priming Exhibits High Remission Rate....Pages 963-966
Immunomodulation and Therapeutic Effects of a Monotherapy with Interleukin-2 as an Induction Therapy in Patients with Poor-Prognosis Acute Myeloid Leukemia....Pages 967-977
Carboplatin-Based High-Dose Therapy for Refractory Acute Myeloid Leukaemia....Pages 978-985
Phase I–II Study of Carboplatin with VP16 and Aracytin for Poor-Risk-Acute Leukemia....Pages 986-991
Front Matter....Pages 993-993
Detection and Quantification of Minimal Residual Disease in Childhood B-Precursor Acute Lymphoblastic Leukemia by Limiting Dilution and PCR Application....Pages 995-1001
Monitoring of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia — Preliminary Data from a Prospective Study....Pages 1002-1006
Clonal Chromosomal Abnormalities in the Stem Cell Compartment of a Patient with Acute Myeloid Leukemia in Hematological Complete Remission....Pages 1007-1011
Front Matter....Pages 993-993
Detection of Minimal Residual Disease in Patients with Acute Myeloid Leukemia....Pages 1012-1019
RT-PCR for the Detection of Minimal Residual Disease in Acute Myeloblastic Leukemia with t(8;21) and t(15;17)....Pages 1020-1025
RT-PCR for the Diagnosis of Acute Myeloblastic Leukemia with Inv(16) and Detection of Minimal Residual Disease....Pages 1026-1030
Monitoring of PML-RAR alpha in Patients with Acute Promyelocytic Leukemia (APL) by RT-PCR....Pages 1031-1036
Detection Limits of Malignant Cells with Leukemia-Associated Phenotype (LAP) in Acute Myeloid Leukemia....Pages 1037-1042
Front Matter....Pages 1043-1043
Interventional Antimicrobial Therapy in Febrile Neutropenic Patients (PEG Study II)....Pages 1045-1049
Management of Infections During Intensified Therapy of Acute Leukemias....Pages 1050-1057
Management of Fever in Adult Hematological Neutropenic Patients: Comparison of Tazocillin + Aminoside versus Ceftazidime + Aminoside in 466 Febrile Episodes....Pages 1058-1063
Management of Febrile Neutropenia in 396 Episodes in Acute Leukemia Patients with Once-Daily Administration of Ceftriaxone....Pages 1064-1070
Failure of Fluconazole Prophylaxis to Reduce Mortality During Treatment for Refractory Acute Myeloid Leukemia: Results of a Phase III Multicenter Study....Pages 1071-1081
Aspergillus terreus Necrotic Chest Skin Lesion in a Case of Acute Myeloid Leukemia....Pages 1082-1086
Local Hydrotherapy as a Treatment Method of Oral Cavity Infections in Children with Acute Leukemias and Lymphomas....Pages 1087-1089
Front Matter....Pages 1091-1091
The Role of BMT in AML in Relation to Prognostic Characteristics....Pages 1093-1096
Early Allogeneic Transplantation Favorably Influences the Outcome of Adult Patients Suffering from Acute Myeloid Leukemia....Pages 1097-1102
Antithymocyte Globulin as Part of the Pretransplant Conditioning Regimen May Reduce Transplant-Related Morbidity and Mortality in Chronic Myelogenous Leukemia Patients Undergoing Allogeneic Bone Marrow Transplantation....Pages 1103-1110
Marrow Transplants from Unrelated Donors for the Treatment of High-Risk Acute Leukemia....Pages 1111-1124
Blood Progenitor Cells and Donor Lymphocyte Transfusion: the New Modes of Marrow Transplantation....Pages 1125-1129
Allogeneic Transplantation of Purified Peripheral Blood Stem Cells from Unrelated Donors....Pages 1130-1133
Ex Vivo Manipulation of Peripheral Blood CD34 + Cells....Pages 1134-1139
Cord Blood Transplantation in Hematopoietic Malignancies....Pages 1140-1148
Front Matter....Pages 1149-1149
Interferon Alpha and Cytosine Arabinoside in the Treatment of Chronic Myelogenous Leukemia....Pages 1151-1157
Alpha-Interferon Role in the Management of Follicular Lymphoma Patients. The GELA Experience....Pages 1158-1162
Treatment of Centroblastic-Centrocytic and Centrocytic Lymphomas at Advanced Stages — Results of the German Low-Grade Lymphoma Study Group....Pages 1163-1168
Quantitative Assessment of the Impact of Interferon Alpha (IFN) vs. Busulfan vs. Hydroxyurea and of Risk Profile on Survival in Chronic Myelogenous Leukemia (CML)....Pages 1169-1177
Interferon Alpha and Beta2 Microglobulin in Multiple Myeloma....Pages 1178-1184
Maintenance with Interferon Alpha in Myeloma....Pages 1185-1192
Back Matter....Pages 1193-1199