CLINICAL STRATEGIES IN HEMATOLOGY

Clinical Medicine 2008H.E. Johnsen

DIAGNOSTIC, PROGNOSTIC AND

THERAPEUTIC STRATEGIES IN HEMATOLOGY

Clinical Medicine 2008H.E. Johnsen

Disease Entities in Hematology

• Benign Hematological Diseases• Red Cells• Leucocytes, Spleen and Immunoglobulins

• Disorders of Hemostasis & Thrombosis• Platelets• Liver, Vascular, Coagulation Factors

• Hematological Malignancies• Stem and Progenitor Cells• Lymph nodes, Spleen and Bone Marrow

Strategies in Hematology

• The Diagnostic and Prognostic Approach

• Complications at Diagnosis

• Principles and Pharmacology of Chemotherapy

• Supportive Care• Immune and Cellulare Therapies

The Diagnostic and Prognostic Approach

• Examination of• Blood• Bone Marrow• Lymph Nodes and Tissue• Spleen

The Diagnostic and Prognostic Approach

• Diagnostic Classification• Scientifically accurate and reproducible• Predict clinical behavior • Incorporate presumed site and cell of origin• The phenotype of the clonal cell• Cell cycle and differentiation stage of the malignant

population.

The Diagnostic and Prognostic Approach

• Modalities of tests• Morphology, including histopatology• Cytology and electron microscopy of needle

aspirations• Immunohisto- and cytochemistry• Cytogenetics and Molecular Genetics (PCR, FISH,

Array)• Plasma protein analysis

Strategies in Hematology

• The Diagnostic and Prognostic Approach

• Complications at Diagnosis

• Principles and Pharmacology of Chemotherapy

• Supportive Care• Immune and Cellulare Therapies

Complications at Diagnosis

Septic shock/Neutropenic feverHypercalcemiaHyperviscosity

LeucostasisDIC

Hemorrhagic diatesisThrombotic Thrombocytopenic Purpura

Paraparesis/Spinal Collapse

Strategies in Hematology

• The Diagnostic and Prognostic Approach

• Complications at Diagnosis

• Principles and Pharmacology of Chemotherapy

• Supportive Care• Immune and Cellulare Therapies

PRINCIPLES OF HEMATOLOGICAL CANCER

TREATMENT The Goal

Cancer BiologyChemo TherapeuticsTreatment Strategies:

Conventional High Dose Therapy & SC Support

Future

The goal of cancer treatment

• First to eradicate the cancer.

• If this primary goal cannot be accomplished, the goal shifts to palliation, the amelioration of symptoms, and preservation of quality of life while striving to extend life.

The problem

• Every cancer treatment has the potential to cause harm, and treatment may be given that produces toxicity with no benefit.

• The therapeutic index of many interventions is quite narrow, and most treatments are given to the point of toxicity.

Main groups of Treatment

• Surgery.

• Radiation therapy.

• Chemotherapy.

• Biologic therapy – including immunotherapy,

– differentiating agents, and

– agents targeting cancer cell biology.

Curability of Hematological Cancers with Chemotherapy

• A. Advanced cancers with possible cure– Acute lymphoid and acute myeloid leukemia (pediatric/adult)– Hodgkin's disease (pediatric/adult)– Lymphomas certain types (pediatric/adult)

• B. Cancers possibly cured with "high-dose" chemotherapy with stem cell support– Relapsed leukemias, lymphoid and myeloid– Relapsed lymphomas, Hodgkin's and non-Hodgkin's– Chronic myeloid leukemia– Multiple myeloma

• E. Cancers responsive with useful palliation, but not cure, by chemotherapy– Chronic myeloid leukemia– Hairy cell leukemia– Chronic lymphocytic leukemia– Lymphoma certain types– Multiple myeloma

Commonly Used Cancer Chemotherapy Agents

• DIRECT DNA-INTERACTING AGENTS

• INDIRECT DNA-INTERACTING AGENTS

Prognosis Based Strategies

• Diagnosis & Prognosis– Induction treatment– Intensification and Consolidation– Maintenance

– Observation

Prognosis Based Strategies

• Diagnosis & Prognosis– Genomics and Proteomics– Response type CR/PR/RD/PD– Minimal Residual Disease (Cytomics)

Principle of Protein arrays

Principle of cDNA-based arrays

Strategies in Hematology

• The Diagnostic and Prognostic Approach

• Complications at Diagnosis

• Principles and Pharmacology of Chemotherapy

• Supportive Care• Immune and Cellulare Therapies

Supportive Care

Strategies in Hematology

• The Diagnostic and Prognostic Approach

• Complications at Diagnosis

• Principles and Pharmacology of Chemotherapy

• Supportive Care• Immune and Cellulare Therapies

Immune and Cellulare Therapies

Passive Immune TherapyVaccination

Adaptive therapyStem Cell transplantation

Graft versus Leukemia Effect

The Principleof

High Dose Therapy

Induction Therapy Control of Disease

Bone Marrow Priming Stem Cell Collection

High dose therapy Cure?

Consolidation Survival?

The Problemsof

High Dose Therapy

Disease Control Non specific high dose regimens

Supportive Care Quality assessment of Grafting

Relapses MRD in Host and/or Graft

Diseases

• Non Hodgkin’s Lymphoma (second remission)• Hodgkin’s Disease (second remission)• Multiple Myeloma (first remission)• Acute Myeloid Leukemia (first remission)• Age <65 years, good performance.

Complications

• Bleeding episodes

• Anemia

• Infections:– Sepsis– Pneumonia– Katheter infections– Virus reactivation

• Toxicity– Enteritis– Mucositis

– Dermatitis– Graft failure

• Relapse• Deaths

Strategies in Hematology

• The Diagnostic and Prognostic Approach

• Complications at Diagnosis

• Principles and Pharmacology of Chemotherapy

• Supportive Care• Immune and Cellulare Therapies