Title: Leukemia in children. Haemolytic Uraemic Syndrome (HUS).
1Leukemia 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.
4Risk 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.
6According 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.
8Immunological 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.
9Shown 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.
10Shown 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.
11Shown 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.
12The 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
13The 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
16Diagnostics 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).
20Patients 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).
21Good 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).
32HUS clinical features
- profuse diarrhoea that turns bloody 1 to 3 days
later and rarely on the first day - fever, abdominal pain and vomiting
33HUS 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
34Therapy of HUS
- Antibiotics confer no benefit, even if given
early - Massive intravenous infusions
- with potassium adding (under urine volume
control)