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    Acute Leukaemias

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    Sambhavi Sangode
    Acute leukemias are cancers of the blood and bone marrow characterized by abnormal proliferation of immature white blood cells. There are two main types: acute myeloid leukemia (AML), caused by malignant transformation of myeloid progenitor cells; and acute lymphocytic leukemia (ALL), caused by transformation of lymphoid progenitor cells. Both can be further classified based on the specific cell line involved. AML is more common in older adults, while ALL is most common in children. Treatment involves chemotherapy to induce remission, consolidation therapy to prevent relapse, and stem cell transplantation in high risk cases. Prognosis depends on various clinical and biological factors.

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    Acute Leukaemias

    Uploaded by

    Sambhavi Sangode
    13 views27 pages
    Acute leukemias are cancers of the blood and bone marrow characterized by abnormal proliferation of immature white blood cells. There are two main types: acute myeloid leukemia (AML), caused by malignant transformation of myeloid progenitor cells; and acute lymphocytic leukemia (ALL), caused by transformation of lymphoid progenitor cells. Both can be further classified based on the specific cell line involved. AML is more common in older adults, while ALL is most common in children. Treatment involves chemotherapy to induce remission, consolidation therapy to prevent relapse, and stem cell transplantation in high risk cases. Prognosis depends on various clinical and biological factors.

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    Acute leukemias are cancers of the blood and bone marrow characterized by abnormal proliferation of immature white blood cells. There are two main types: acute myeloid leukemia (AML), caused by malignant transformation of myeloid progenitor cells; and acute lymphocytic leukemia (ALL), caused by transformation of lymphoid progenitor cells. Both can be further classified based on the specific cell line involved. AML is more common in older adults, while ALL is most common in children. Treatment involves chemotherapy to induce remission, consolidation therapy to prevent relapse, and stem cell transplantation in high risk cases. Prognosis depends on various clinical and biological factors.

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    Download as pptx, pdf, or txt
    13 views27 pages

    Acute Leukaemias

    Uploaded by

    Sambhavi Sangode
    Acute leukemias are cancers of the blood and bone marrow characterized by abnormal proliferation of immature white blood cells. There are two main types: acute myeloid leukemia (AML), caused by malignant transformation of myeloid progenitor cells; and acute lymphocytic leukemia (ALL), caused by transformation of lymphoid progenitor cells. Both can be further classified based on the specific cell line involved. AML is more common in older adults, while ALL is most common in children. Treatment involves chemotherapy to induce remission, consolidation therapy to prevent relapse, and stem cell transplantation in high risk cases. Prognosis depends on various clinical and biological factors.

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    © All Rights Reserved
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    of 27

    ACUTE LEUKAEMIAS

    LEUKAEMIA

     LEUKAEMIAS ARE THE GROUP OF DISORDERS CHARACTERIZED BY


    MALIGNANT TRANSFORMATION OF THE BLOOD FORMING CELLS.

     IT MAY INVOLVE ANY OF THE CELL LINES OR A STEM CELL COMMON TO


    SEVERAL CELL LINES.
     LEUKAEMIAS ARE CLASSIFIED INTO TWO MAJOR GROUPS:

     ACUTE LEUKAEMIA

     CHRONIC LEUKAEMIA
     BOTH ACUTE AND CHRONIC LEUKAEMIAS ARE FURTHER CLASSIFIED
    ACCORDING TO THE PROMINENT CELL LINES

     MYELOID SERIES: MYELOCYTIC LEUKAEMIA


     LYMPHOID SERIES: LYMPHOCYTIC LEUKAEMIA
     FOUR BASIC TYPES:

     ACUTE MYELOCYTIC LEUKAEMIA


     ACUTE LYMPHOCYTIC LEUKAEMIA
     CHRONIC MYELOCYTIC LEUKAEMIA
     CHRONIC LYMPHOCYTIC LEUKAEMIA
    ACUTE MYELOCYTIC LEUKAEMIA

     ACUTE MYELOID LEUKAEMIA IS A TUMOR OF HEMATOPOIETIC


    PROGENITORS CAUSED BY ACQUIRED ONCOGENIC MUTATIONS THAT
    IMPEDE DIFFERENTIATION, LEADING TO THE ACCUMULATION OF
    IMMATURE MYELOID BLASTS IN THE MARROW.

     ALSO KNOWN AS ACUTE MYELOGENOUS LEUKAEMIA OR ACUTE NON-


    LYMPHOCYTIC LEUKAEMIA.

     OCCURS AT ALL AGES, PEAKS AFTER 60 YEARS OF AGE.


    ETIOLOGY

     HEREDITY:
    - DOWN SYNDROME
    - FANCONI ANEMIA
    - CONGENITAL NEUTROPENIA
     RADIATIONS:
    - HIGH DOSE RADIATION (ATOMIC BOMB SURVIVORS)
     CHEMICAL AND OCCUPATIONAL EXPOSURE:
    -BENZENE
    -PETROLEUM PRODUCTS
    -ETHYLENE OXIDE
     DRUGS:
    -ALKYLATING AGENTS
    -TOPOISOMERASE II INHIBITORS
    -CHLOROQUINE
    PATHOGENESIS

     DRIVER MUTATIONS IN AML TEND TO FALL INTO FOUR FUNCTIONAL


    CATEGORIES:

     TRANSCRIPTION FACTOR MUTATIONS THAT INTERFERE WITH NORMAL


    MYELOID DIFFERENTIATION.
     MUTATION OF SIGNALLING PROTEINS THAT RESULT IN CONSTITUTIVE
    ACTIVATION OF PROGROWTH/SURVIVAL PATHWAYS.
     MUTATION OF GENE THAT REGULATE OR MAINTAIN THE EPIGENOME
     MUTATION OF TP53 OR GENES THAT REGULATE P53.
    CLINICAL PRESENTATION

     NONSPECIFIC SYMPTOMS
     FATIGUE
     ANOREXIA
     WEIGHT LOSS
     FEVER
     BLEEDING,EASY BRUISING
     BONE PAIN,LYMPHADENOPATHY, NONSPECIFIC COUGH,HEADACHE
    PHYSICAL FINDINGS

     FEVER
     SPLENOMEGALY
     HEPATOMEGALY
     LYMPHADENOPATHY
     STERNAL TENDERNESS
     EVIDENCE OF INFECTION AND HEMORRHAGE
    ACUTE LYMPHOCYTIC LEUKEMIA

     ACUTE LYMPHOCYTIC LEUKEMIA ARE NEOPLASMS COMPOSED OF


    IMMATURE B(PRE-B)OR T(PRE-T)CELLS ,WHICH ARE REFERRED TO AS
    LYMPHOBLASTS
     ACUTE LYMPHOCYTIC LEUKEMIA IS THE MOST COMMON TYPE OF CANCER
    IN CHILDREN
    SIGNS AND SYMPTOMS

     GENERALISED WEAKNESS AND FATIGUE


     ANEMIA
     FREQUENT OR UNEXPLAINED FEVER AND INFECTION
     WEIGHT LOSS AND LOSS OF APPETITE
     BONE PAIN,JOINT PAIN
     BREATHLESSNESS
     ENLARGED LYMPH NODES,LIVER OR SPLEEN
     PITTING EDEMA IN THE LOWER LIMBS
     PETECHIAE
    PATHOGENESIS

     DAMAGE TO DNA THAT LEADS TO UNCONTROLLED CELLULAR GROWTH


    AND SPREAD THROUGHOUT THE BODY
     DAMAGE CAN BE CAUSED THROUGH THE FORMATION OF FUSION GENE AS
    WELL AS THE DYSREGULATION
     THIS DAMAGE MAY BE CAUSED BY ENVIRONMENTAL FACTORS SUCH AS
    CHEMICALS,DRUGS OR RADIATION
     SOME EVIDENCE SUGGEST THAT SECONDARY LEUKEMIA CAN DEVELOP IN
    INDIVIDUALS TREATED FOR OTHER CANCERS WITH RADIATION AND
    CHEMOTHERAPY, AS A RESULT OF THAT TREATMENT
    INVESTIGATIONS

     BLOOD EXAMINATION:
    ANEMIA WITH NORMAL OR RAISED MCV
    LEUKOCYTE COUNT: VARIES FROM 1* 10
    SEVERE THROMBOCYTOPENIA
     BONE MARROW EXAMINATION:
    USUALLY HYPERCELLULAR WITH REPLACEMENT OF NORMAL ELEMENTS BY
    LEUKAEMIC BLAST CELLS IN VARYING DEGREES.
    PRESENCE OF AUER RODS – INDICATES THE MYELOBLASTIC TYPE OF LEUKAEMIA
    MANAGEMENT

     SPECIFIC THERAPY:

    THE AIM OF TREATMENT IS TO DESTROY THE LEUKAEMIC CLONE OF CELLS


    WITHOUT DESTROYING THE RESIDUAL NORMAL STEM CELL COMPARTMENT.
    3 PHASES:
    REMISSION INDUCTION: IN THIS PHASE A FRACTION OF TUMOR IS
    DESTROYED BY COMBINATION CHEMOTHERAPY
    THE AIM IS TO ACHIEVE REMISSION, A STATE IN WHICH THE BLOOD COUNTS
    RETURN TO NORMAL AND THE MARROW BLAST COUNT IS LESS THAN 5%.
     REMISSION CONSOLIDATION: THIS CONSISTS OF A NUMBER OF COURSES
    OF CHEMOTHERAPY, RESULTING IN PERIODS OF MARROW HYPOPLASIA.
    IN POOR PROGNOSIS LEUKAEMIA, THIS MAY INCLUDE ALLOGENIC HSCT
     REMISSION MAINTENANCE: TREATMENT CONSISTING OF REPEATING
    CYCLES OF DRUG ADMINISTRATION.
    THIS MAY EXTEND FOR UPTO 3 YEARS IF RELAPSE DOES NOT OCCUR.
     IN PATIENTS WITH ALL IT IS NECESSARY TO GIVE PROPHYLACTIC
    TREATMENT TO THE CNS. IT USUALLY CONSIST OF COMBINATION OF
    CRANIAL IRRADIATION, INTRATHECAL CHEMOTHERAPY AND HIGH DOSE
    METHOTREXATE, WHICH CROSS THE BLOOD BRAIN BARRIER.
     SUPPORTIVE THERAPY:
    • ANEMIA: TREATED WITH RED CELL CONCENTRATE TRANSFUSIONS.
    • BLEEDING: THROMBOCYTOPENIC BLEEDING REQUIRES PLATELET
    TRANSFUSIONS.
    • INFECTIONS: FEVER LASTING OVER 1 HR IN A NEUTROPENIC PATIENT
    INDICATES POSSIBLE SEPSIS THEREFORE REQUIRES PARENTERAL
    ADMINISTRATION OF BROAD SPECTRUM ANTIBIOTICS.
    IN CASE OF LOCAL BACTERIOLOGICAL RESISTANCE COMBINATION WITH
    AMINOGLYCOSIDES, BROAD SPECTRUM PENICILLIN OR SINGLE AGENT BETA
    LACTAM CAN BE USED.
    • METABOLIC PROBLEMS:
    RENAL FAILURE – ALLOPURINOL AND INTRAVENOUS HYDRATION. IN PATIENTS
    WITH HIGH RISK OF TUMOR LYSIS SYNDROME PROPHYLACTIC RASBURICASE
    ( A RECOMBINANT URATE OXIDASE ENZYME ) IS USED. OCCASIONALLY,
    DIALYSIS MAY BE REQUIRED.
     HEMATOPOEITIC STEM CELL TRANSPLANTATION:
    IN PATIENTS WITH HIGH RISK OF ACUTE LEUKEMIA, ALLOGENIC HSCT CAN
    IMPROVE 5 YEAR SURVIVAL FROM 20% TO AROUND 50%.
    REDUCED INTENSITY CONDITIONING AS ALLOWED HSCT TO BE DELIVERED TO
    A HIGHER PROPTION OF PATIENTS WITH ACUTE LEUKEAMIAS, UPTO THE AGE
    OF ABOUT 65 YEARS.
    PROGNOSIS

     AML: POOR PROGNOSIS

    AGE: >60 YEARS


    SEX: MALE OR FEMALE
    PRESENTING WBC: >50000
    CNS DISEASE AT PRESENTATION: PRESENCE OF BLAST IN CSF
    REMISSION PROBLEM: 20% BLAST IN BONE MARROW AFTER FIRST COURSE.
    CYTOGENETICS: DELETION OR MONOSOMY OF CHROMOSOME 5 AND 7 OR
    COMPLEX CHROMOSOMAL ABNORMALITIES.
     ALL: POOR PROGNOSIS

    AGE: <1 YEAR OR >10 YEARS.


    SEX: MALE
    PRESENTING WBC: 50000
    CNS DISEASE AT PRESENTATION; PRESENCE OF BLASTS IN CSF
    REMISSION PROBLEMS: FAILURE TO REMIT AFTER FIRST INDUCTION
    TREATMENT.
    CYTOGENETICS: PHILADELPHIA POSITIVE
    THANK YOU

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