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Leukemia in children. Haemolytic Uraemic Syndrome (HUS). Sakharova Inna. Ye., MD, Univ. assistant Acute lymphoblastic leukaemia (ALL) is a malignant transformation of ... – PowerPoint PPT presentation

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Title: Leukemia in children. Haemolytic Uraemic Syndrome (HUS).


1
Leukemia in children. Haemolytic Uraemic Syndrome
(HUS).
  • Sakharova Inna. Ye., MD,
  • Univ. assistant

2
(No Transcript)
3
  • Acute lymphoblastic leukaemia (ALL) is a
    malignant transformation of a clone of cells from
    the bone marrow where early lymphoid precursors
    proliferate and replace the normal cells of the
    bone marrow.

4
Risk factors for the development of childhood
leukemia
  • Heredity (presence of inherited genetic
    syndromes, for example Down syndrome or ataxia
    telangiectasia, presence of cytogenetic
    abnormalities )
  • Environmental factors (ionizing radiation and
    electromagnetic fields, parental use of alcohol
    and tobacco)

5
  • The conclusion of the USA National Radiological
    Protection Board is Laboratory experiments have
    provided no good evidence that extremely low
    frequency electromagnetic fields are capable of
    producing cancer, nor do human epidemiological
    studies suggest that they cause cancer in
    general. There is, however, some epidemiological
    evidence that prolonged exposure to higher levels
    of power frequency magnetic fields is associated
    with a small risk of leukaemia in children. In
    practice, such levels of exposure are seldom
    encountered by the general public in the UK. In
    the absence of clear evidence of a carcinogenic
    effect in adults, or of a plausible explanation
    from experiments on animals or isolated cells,
    the epidemiological evidence is currently not
    strong enough to justify a firm conclusion that
    such fields cause leukaemia in children.

6
According to the French-American-British (FAB)
classification, leukemic lymphoblasts in ALL
subdivide into three categories
  • L1 lymphoblasts are small cells with homogeneous
    chromatin, regular nuclear shape, small or absent
    nucleolus, and scanty cytoplasm. This subtype is
    the most common in children with ALL.
  • L2 lymphoblasts are large and heterogeneous
    cells, heterogeneous chromatin, irregular nuclear
    shape, and nucleolus often large. They are much
    less common than L1 cells and are sometimes
    mistaken for myeloblasts.

7
  • L3 lymphoblasts are large and homogeneous cells
    and cytoplasmic vacuolisation that often overlies
    the nucleus as the most prominent feature. This
    is just 1 to 2 of cases.

8
Immunological classification (on the basis of
immunophenotype)
  • Non-T, non-B cell ALL accounts for 80 of all
    cases
  • Malignancy of B cell precursors
  • B-cell ALL
  • T-cell ALL.

9
Shown here is bone marrow aspirate from a child
with B-precursor acute lymphoblastic leukemia.
Note that the marrow is replaced primarily with
small, immature lymphoblasts that show open
chromatin, scant cytoplasm, and a high
nuclear-cytoplasmic ratio.
10
Shown here is bone marrow aspirate from a child
with T-cell acute lymphoblastic leukemia. The
marrow is replaced with lymphoblasts of varying
size. No myeloid or erythroid precursors are
seen. Megakaryocytes also are absent.
11
Shown here is bone marrow aspirate from a child
with B-cell acute lymphoblastic leukemia. The
lymphoblasts are large and have basophilic
cytoplasm with prominent vacuoles.
12
The first symptoms of acute leukemia are
  • Tiredness, irritability
  •   Intermittent fever
  • Failure to thrive (poor growth)
  •   Bleeding from gums/nose
  •   Easy bruising
  •   Bone pain
  •   Headache
  •   Nausea/vomiting with CNS involvement

13
The signs of acute leukemia during examination
are
  • Skin pallor, tachycardia and a flow murmur may be
    obvious because of anemia presence.
  • Signs of infection can be non-specific like fever
    or pneumonia may be present.
  • Thrombocytopenia often causes petechiae on the
    lower limbs. Disseminated intravascular
    coagulation (DIC) may aggravate the situation and
    cause larger ecchymoses. Petechiae are small
    dots, purpura is larger and ecchymoses are larger
    bruises.

14
  • Hepatomegaly may be found.
  • Lymphomatous features massive splenomegaly,
    anterior mediastinal mass, massive
    lymphadenopathy.
  • Leukaemia cutis is an uncommon condition due to
    infiltration of the skin.
  • Superior vena cava syndrome is caused by
    mediastinal adenopathy compressing the superior
    vena cava. A prominent venous pattern develops
    over the upper chest from collateral vein
    enlargement. The face may appear plethoric and
    the periorbital area may be edematous.

15
  • Involvement of sanctuary sites 1) CNS
    involvement manifests as diffuse meningeal
    infiltration with signs of increased intracranial
    pressure 2) testes, one or both of which may be
    involved, with infiltration producing enlargement
    that is out of proportion to the childs sexual
    development

16
Diagnostics of ALL
  • General blood count normochromic anaemia with a
    low reticulocyte index, thrombocytopenia,
    neutropenia, different WBC count (leucopenia or
    hyperleucocytosis), presence of lymphoblasts
  • Bone marrow aspiration and biopsy (sternal
    puncture) are the definitive diagnostic tests to
    confirm the diagnosis more than 25 of
    lymphoblasts prove the diagnosis of ALL

17
  • Bone marrow samples should undergo cytogenetics
    and flow cytometry for identification of the type
    of leukemia
  • DIC may occur and this produces an elevated
    prothrombin time, reduced fibrinogen level and
    the presence of fibrin degradation products in
    coagulogram
  • Lactic dehydrogenase levels (LDL) are usually
    raised and rapid cell turnover may raise uric
    acid in biochemical blood test

18
  • Lumbar puncture with cytospin morphologic
    analysis This is performed before systemic
    chemotherapy is administered to assess the
    presence of CNS involvement and to administer
    intrathecal chemotherapy.
  • Liver and renal function (ultrasonography) must
    be checked before initiating chemotherapy
  • CXR may show pneumonia or an enlarged mediastinal
    mass

19
  • Multiple gated acquisition (MUGA) scan is
    required because many chemotherapeutic agents
    used in treatment are cardiotoxic, ECG is also
    necessary
  • Molecular techniques, including
    reverse-transcriptase polymerase chain reaction
    (RT-PCR), Southern blot analysis, and
    fluorescence in situ hybridization (FISH).

20
Patients can be divided into 3 groups on the
basis of risk (The Childrens Cancer Group)
  • Good prognosis (have 80 or greater chance of
    cure) age between 2 and 10 years, WBC ? 10 G/L,
    absence of L3 cells, absence of lymphomatous
    features, platelet count greater 100 G/L.
  • Poor prognosis (have less than 50 chance of
    cure) age less than 1 year old or greater than
    10 years old, WBC ? 50 G/L, presence of
    chromosomes translocations, B cell ALL with L3
    cells, blasts with T-cell phenotype.
  • intermediate prognosis (have 50 or greater
    chance of cure).

21
Good prognosis for those who have brisk initial
response to therapy
  • The Childrens Cancer Group found an improved
    prognosis in patients with less than 5 blasts
    in the bone marrow after seven days of
    chemotherapy.
  • The Berlin-Frankfurt-Münster group found a
    similar prognosis in patients who had less than
    1000 blasts/ml in the peripheral blood after
    seven days of prednisone.

22
  • With the exception of B-cell ALL, the treatment
    of childhood ALL may be considered in three
    categories
  • Induction of remission
  • Consolidation of remission
  • Maintenance of remission
  • and all stages involve treatment with cytotoxic
    agents and steroids varying in intensity. In some
    books
  • 4. The treatment of subclinical CNS leukemia
  • is divided into special category also.

23
  • Induction is by quadruple therapy with
    vincristine, prednisolone, anthracycline, and
    cyclophosphamide or L-asparaginase or a 5-drug
    regimen of vincristine, prednisolone,
    anthracycline, cyclophosphamide, and
    L-asparaginase. Intrathecal metotrexate is used
    in proper days also. It is given over the course
    of 4 to 6 weeks. This type of therapy induces
    complete remission in more than 95 of patients.

24
  • The main sign of remission is less than 5 of
    blasts in bone marrow additionally it should be
    less than
  • 50 of lymphocytes in peripheral blood.

25
  • This is usually followed by consolidation
    therapy often in the form of dexamethasone,
    vincristine, and doxorubicin, followed by
    cyclophosphamide, anthracycline, and
    6-thioguanine beginning at week 20. In this phase
    of therapy, the drugs are used at higher doses
    than during induction. Consolidation therapy,
    first used successfully in the treatment of
    patients with high-risk disease, also appears to
    improve the long-term survival of patients with
    standard-risk disease.

26
  • Maintenance therapy often consists of
    periodic reinduction pulses of prednisone and
    vincristin as well as
  • 1) Daily oral 6-merkaptopurine and weekly oral
    methotrexate for low-risk patients
  • 2) More intensive multiagent therapy for
    intermediate- and poor-risk patients.

27
  • Relapses still occur in 30-40 of patients.
    If relapse occurs in the CNS or testes, many
    children can still be cured with irradiation and
    additional chemotherapy. If relapse occurs in the
    marrow within 18 months of diagnosis, the chance
    of cure with either chemotherapy or stem cell
    transplantation is less than 10 .

28
  • Bone marrow transplantation is used rather
    more in children than in adults. If a
    first-degree relative with a HLA match is not
    available it is possible to use autologous (own)
    bone marrow rather than allogeneic (donor)
    marrow. However, the results of autologous are
    inferior to sibling donors and a study gave 3
    years survival after remission and bone marrow
    transplant of 26 with autologous bone marrow
    compared with 68 with donor marrow.

29
  • Primary features of tumor lysis syndrome
    include hyperuricemia (due to metabolism of
    purines), hyperphosphatemia, hypocalcemia, and
    hyperkalemia.

30
  • Haemolytic Uraemic Syndrome (HUS) ? a triad of
    microangiopathic haemolytic anaemia (Coombs test
    negative), thrombocytopenia and acute renal
    failure.

31
  • HUS has been associated with E. coli with
    somatic (O) antigen 157 and flagella (H) antigen
    7. It produces a toxin called shiga and hence
    this group is called Shiga-toxin-producing
    Escherichia coli (STEC). An alternative name is
    vero toxin-producing Escherichia coli (VTEC).

32
HUS clinical features
  • profuse diarrhoea that turns bloody 1 to 3 days
    later and rarely on the first day
  • fever, abdominal pain and vomiting

33
HUS diagnostic criteria include
  • packed cell volume of less than 30
  • evidence of erythrocyte destruction on peripheral
    blood smear
  • platelet count less than 150 x 109/L
  • serum creatinine above the upper limit for age
  • haemoglobinuria

34
Therapy of HUS
  • Antibiotics confer no benefit, even if given
    early
  • Massive intravenous infusions
  • with potassium adding (under urine volume
    control)
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