SVIBOR - Project code: 3-01-075

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

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Project code: 3-01-075


LEUKAEMIA


Main researcher: NEMET, DAMIR (171702)


Assistants
Type of research: applied
Duration from: 01/01/91. to 12/31/94.
Papers on project (total): 43
Papers on project quoted in Current Contents: 20
Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: University Hospital Rebro and School of Medicine Department of Medicine Division of Haematology
Address: Kišpatićeva 12
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)41 23-33-68
Phone: 385 (0)41 23-32-33/631
Fax: 385 (0)41 23-33-68
Summary: This project includes the studies on therapy, disease biology, and clinical characteristics of patients with acute leukaemias, chronic myeloid leukaemia and myelodysplastic syndrome. There are three main topics of the project: 1. evaluation of the efficacy of the new therapeutical approaches in each group of diseases - chemotherapy, autologous or allogeneic bone marrow transplantation, therapy with haematopoietic growth factors or other cytokines with possible antitumour or immunomodulatory effect; 2. evaluation of the significance of diagnostic laboratory methods and assays (immunophenotyping, cytogenetics, mollecular biology assays and bone marrow culture) for the more precise diagnosis and classification of the disease, prediction of prognosis and detection of minimal residual disease; 3. evaluation of the incidence of infectious and other complications appearing in the patients with haematological malignancies and methods for their prevention and treatment.

Keywords: Leukaemia, acute myelogenous, acute lymphoblastic, chronic myelogenous, myelodysplasias, chemotherapy, cytokines, bone marrow transplantation

Research goals: 1. RESEARCH ON THE NEW THERAPEUTICAL MODALITIES 1.1. ACUTE LEUKAEMIA (AL) 1.1.1. Evaluation of the efficacy of two different induction chemotherapy protocols on the rate of complete remission 1.1.2. Evaluation of the role (efficacy and toxicity) of various forms of intensive postremission therapy: intensive consolidation chemotherapy (CT), autologous bone marrow transplantation (ABMT) or allogeneic bone marrow transplantation (alloBMT) in improving survival in patients with AL 1.1.3. Evaluation of efficacy and toxicity of intensive consolidation CT in comparison with conventional maintenance CT in patients over 45 years of age in whom alloBMT is unsuitable 1.1.4. Evaluation of the efficacy and toxicity of two forms of maintenance CT in patients more than 60 years of age in whom intensive treatment is unsuitable 1.1.5. Research on the prognostic factors important for achievement of complete remission (CR), prediction of success of postremission therapy, duration of CR, and survival of patients 1.1.6. Evaluation of the role of new chemotherapeutic agents in the treatment of relapsed or refractory AL 1.2. CHRONIC MYELOID LEUKAEMIA (CML) 1.2.1. Evaluation of the role of Interferon-alpha in comparison to chemotherapeutic agents on the duration of the chronic phase CML 1.2.2. Evaluation of the incidence and significance of Ph1+/Ph1- mosaicism during chronic phase CML achieved either by Interferon-alpha or with intensive chemotherapy 1.2.3. Research on the possibilities for the treatment of the selected patients with Ph1+/Ph1- mosaicism with ABMT 1.2.4. In a prospective comparative study, to estimate the role (efficacy and toxicity) of chemotherapy in comparison with BMT during the chronic phase CML 1.2.5. Research on the possibilities for the treatment of patients without HLA-compatible sibling donor with BMT from HLA-compatible unrelated volunteer donor. Institute the relationship and cooperation with the volunteer donor registries in the foreign countries 1.2.6. Explore and analyze prognostic factors in chronic phase CML 1.3. MYELODYSPLASTIC SYNDROME (MDS) 1.3.1. Evaluation of the efficacy and toxicity of the granulocyte-macrophage colony stimulating factor (GM-CSF) alone or in combination with cytosine-arabinoside in low or high risk MDS 1.3.2. Evaluation of the role of other cytokines (interleukin-3) in the treatment of MDS 2. EXPLORATION OF MORPHOLOGICAL, FUNCTIONAL, IMMUNOLOGICAL, AND CYTOGENETIC CHARACTERISTICS OF LEUKAEMIAS AND MDS AND THEIR VALUE IN THE DETECTION OF MINIMAL RESIDUAL DISEASE 2.1. Analysis of cytomorphological and immunophenotipic characteristics of AL and evaluation of their significance for the classification and prognosis of AL and MDS 2.2. Establish various bone marrow culture systems and explore the growth characteristics of haematopoietic stem cells in vitro in health and disease. Evaluate the role of in vitro bone marrow culture for the assessment of the cryopreserved bone marrow quality and viability before ABMT as well as prediction of haematopoietic recovery after ABMT 2.3. Analysis of cytogenetic changes in neoplastic haematopoietic cells in patients with AL and MDS, evaluation of their incidence and significance for the diagnosis, prediction of the therapeutic response and prognosis, the role of cytogenetic follow-up in various disease states (KML, acute promyelocytic leukaemia (APL), etc.) 2.4. Introduce the methods of molecular biology for the detection of several important cellular oncogene, evaluate incidence of some oncogenes in AML, and their significance for the diagnosis of AML. In KML and APL analyze clinical significance of specific oncogenes translocation. 2.5. With the combination of several methods - morphology, immunophenotyping, bone marrow culture, cytogenetics and molecular biology explore the possibilities for the detection of minimal residual diseases in remission. 3. ANALYSIS OF THE INCIDENCE, PREVENTION AND TREATMENT OF COMPLICATIONS OCCURRING IN ACUTE LEUKAEMIA AND MDS PATIENTS 3.1. Evaluation of the incidence and type of bacterial, fungal, and viral infections in vivo and post mortem in granulocytopenic and other immunocompromised patients 3.2. In prospective study evaluate the validity of prophylactic antibiotic treatment in the prevention of gram-negative infections in granulocytopenic patients 3.3. Evaluation of the role of haematopoietic growth factors administered in granulocytopenic patients after intensive chemotherapy or BMT on the reduction of serious bacterial and fungal infection 3.4. Evaluation of the incidence and significance of coagulation disorders in AL EXPECTED RESULTS AND ACHIEVEMENTS 1. Advancement in the knowledge on better remission induction treatment as well as on the results achieved by different schemes of induction remission therapy; as a result a higher proportion of patients in complete remission in various age groups 2. Identification of precise role of each of intensive postremission treatment modalities - chemotherapy, AMBT and alloBMT in the treatment of leukaemia and MDS, and clarification of indications for the treatment of particular diseases or group of patients with particular treatment modalities 3. Using this selected approach in the treatment of leukaemia and MDS, a higher proportion of patients with prolonged survival or cure could be expected 4. Improvement of the treatment results of refractory and relapsed AL by a proper evaluation of efficacy of the new antitumour agents 5. Improvement of treatment results in the chronic phase CML by introducing and evaluating the role of new therapeutic modalities like alpha-interferon and ABMT 6. Knowledge improvement about the influence of haematopoietic growth factors on the normal and leukaemic haematopoiesis in vivo 7. Knowledge improvement about the morphological and functional characteristics of normal and leukaemic haematopoiesis 8. Introduction and proper evaluation of methods for the detection of minimal residual disease, thus making the basis for efficient eradication of residual disease in remission 9. Konowledge improvement about the factors important for the prediction of treatment success and disease outcome allowing different treatment approachs to the different prognostic group of patients 10. Reduction in the incidence of serious infectious and non-infectious complications by achieving a new information on their prophylaxis and proper treatment 11. Introduction of new laboratory and clinical technologies in the diagnosis and treatment of neoplastic haematological diseases 12. Research within this project will improve the nouveau of scientific and routine work in the clinical department and laboratory services in general not only in haematology but also in other services

COOPERATION - PROJECTS


  1. Name of project: 3-01-074 TRANSPLANTACIJA KOŠTANE SRŽI
    Name of institution: Zavod za hematologiju, Klinika za unutarnje bolesti, Klinički bolnički centar Rebro, Zagreb
    City: 10000 - Zagreb, Croatia

COOPERATION - INSTITUTIONS


  1. Name of institution: Odjel za hematologiju, Klinika za unutarnje bolesti Medicinskog fakulteta, Klinička bolnica Merkur
    Type of institution: University/Faculty
    Type of cooperation: Joint project
    City: 10000 - Zagreb, Croatia

  2. Name of institution: Department of Haematology, University College Hospital
    Type of institution: International organization
    Type of cooperation: Systematic exchange of information
    City: London, United Kingdom

  3. Name of institution: Service d'Hematologie, Hopital St Antoine
    Type of institution: International organization
    Type of cooperation: Systematic exchange of information
    City: Paris, France

  4. Name of institution: EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER-Leukaemia group
    Type of institution: International organization
    Type of cooperation: Joint project
    City: Brusseles, Belgija

  5. Name of institution: EUROPEAN ORGANIZATION FOR BLOOD AND MARROW TRANSPLANTATION
    Type of institution: International organization
    Type of cooperation: Systematic exchange of information
    City: BASEL, SWITZERLAND

  6. Name of institution: INTERNATIONALE GESSELSCHAFT FUER CHEMO-IMMUNOTHERAPIE
    Type of institution: International organization
    Type of cooperation: Joint project
    City: BEČ, AUSTRIA

  7. Name of institution: EORTC-INVASIVE FUNGAL INFECTION GROUP
    Type of institution: International organization
    Type of cooperation: Systematic exchange of information
    City: Brusseles, Belgija
Other information about the project.
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