Acute Myelogenous Leukemia in Childhood: Implications of Therapy Studies for Future Risk-Adapted Treatment Strategies

ISBN-13: 9783540520702 / Angielski / Miękka / 1990 / 163 str.

Ursula Creutzig; Jarg Ritter; Gunther Schellong

Opis

The results of treatment for childhood acute myelogenous leukemia (AML) have improved considerably during the last ten years. This progress was demonstrated by the two consecutive multicenter studies, AML-BFM-78 and -83, in which almost identical extended multi drug regimes of che motherapy were administered for eight weeks and followed up by two years maintenance. The main difference in the second study was the addition of an eight-day intensive in duction course. Due to this new element, the relapse rate was reduced significantly. Another result of the BFM-83 study was the definition of two risk groups on the basis of standardized treatment, which has lead to a risk-adapted treatment strategy in the third ongoing trial, AML-BFM- 87. This improvement was only possible thanks to the coop eration of pediatricians, physicians, radiotherapists, statisti cians, and especially the staff at the hospitals and reference laboratories. Thus, we would like to thank everyone who has been involved in these studies and hope that they will be further encouraged to improve treatment strategies for AML in children. The coordination, enforcement, and analyses of the stud ies would not have been possible without the financial sup port of the Federal Ministry for Research and Technology of the FRG. We are grateful for the generous contributions supporting this book from Lederle and Farmitalia. Munster, April 1990 Ursula Creutzig Jorg Ritter Gunther Schellong Contents 1 Introduction . . . . .. . . . . . . . . . . . . . . .. . . . 1 ."

Spis treści

1 Introduction.- 1.1 Development of AML Therapy in Children.- 1.1.1 Historical Development.- 1.2 Prognostic Parameters in AML.- 1.3 Objectives of the Analysis.- 2 Patients and Therapy.- 2.1 Patient Eligibility.- 2.2 Therapy Schedule for Study AML-BFM-78.- 2.3 Therapy Schedule for Study AML-BFM-83.- 3 Definitions and Methods.- 3.1 Definitions.- 3.2 Diagnostic Methods.- 3.3 Statistical Methods.- 4 Results.- 4.1 Analysis of Pretherapeutic Patient Data.- 4.1.1 Total Group.- 4.1.2 FAB Subtypes.- 4.1.3 Morphologic and Laboratory Findings.- 4.2 Correlation of Initial Parameters Including Kinetics of Blast Cell Reduction.- 4.3 Outcome.- 4.4 Results by Morphologic Subtypes.- 4.5 Risk Factor Analysis of Pretherapeutic and o Response-Kinetic Parameters.- 4.5.1 Sex.- 4.5.1.1 Influence of Sex in the FAB Types.- 4.5.2 Age at Diagnosis.- 4.5.2.1 Influence of Age in the FAB Types.- 4.5.3 White Blood Cell and Blast Count.- 4.5.3.1 Influence of WBC on Prognosis in the FAB Types.- 4.5.3.2 Initial Blast Count.- 4.5.4 Initial CNS Involvement.- 4.5.5 Extramedullar Organ Involvement.- 4.5.6 Other Pretherapeutic Variables.- 4.5.6.1 Morphologic Variables: Auer Rods and Eosinophilia.- 4.5.6.2 Cytochemical, Immunological, Flow Cytometric, and Cytogenetic Findings.- 4.5.7 Parameters of Response Kinetics.- 4.5.7.1 Blast Reduction in the BM.- 4.5.7.2 Time Until CR.- 4.5.8 Prognostic Relevance of Pretherapeutic and Response-Kinetic Parameters: Cox Analyses.- 4.5.8.1 Results of AML-BFM-78 Study.- 4.5.8.2 Results of AML-BFM-83 Study.- 4.5.8.3 Results by FAB Group Allocation of AML-BFM-83 Study.- 4.5.8.4 Results by Individual FAB Types.- 4.5.8.5 Relationship Between the Implementation of Therapy and Pretherapeutic Prognostic Parameters.- 4.6 Early Death Due to Hemorrhage and/or Leukostasis and Other Complications.- 4.6.1 Early Death Due to Hemorrhage and/or Leukostasis.- 4.6.2 Early Death Due to Other Complications Within the First Six Weeks After Onset of Therapy.- 4.7 Analysis of the Implementation of Therapy in AML-BFM-83 Study.- 4.8 Toxicity During the Individual Therapy Phases of AML-BFM-83 Study.- 4.8.1 Complications During Induction.- 4.8.2 Complications During Consolidation.- 4.8.3 Complications During Maintenance.- 4.8.4 Summary of Lethal Complications.- 5 Discussion.- 5.1 Clinical and Morphologic Characteristics of Childhood AML.- 5.1.1 Epidemiological Factors.- 5.1.2 Clinical Data.- 5.2 Characterization of the FAB Types M1-M7 in Children by Pretherapeutic Parameters.- 5.3 Evaluation of the Relationship Between Pretherapeutic Parameters.- 5.4 Prognostic Relevance of Pretherapeutic Parameters and Response Kinetics: Definition of Prognostic Groups.- 5.4.1 Clinical Parameters.- 5.4.2 Morphologic Parameters.- 5.4.3 Cytogenetics.- 5.4.4 Response Kinetics.- 5.4.5 Prognostic Groups in Childhood AML.- 5.5 Influence of Therapy on the Prognostic Relevance of Pretherapeutic Parameters: Evaluating the Introduction of ADE Induction Therapy in AML-BFM-83 Study.- 5.6 Early Death Due to Hemorrhage and/or Leukostasis and Other Complications: Consequences for Initial Therapy.- 5.7 Relationship Between Implementation of Therapy, Complications, and Course.- 5.8 Perspectives for Future Prognosis-Adapted Therapy Strategies.- 5.8.1 Early Death Due to Hemorrhage and/or Leukostasis.- 5.8.2 Nonresponders.- 5.8.3 Relapses.- 5.8.4 Additional Chemotherapy.- 5.8.5 Allogeneic BMT in First CR.- 5.8.6 Autologous BMT.- 5.8.7 Measures for Reduction of Toxicity.- 5.8.8 Modification of the CNS Prophylaxis.- 5.8.9 Concluding Remarks.- 6 Summary.- 7 References.- 8 Appendix.- 9 Subject Index.