The document discusses childhood leukemia, describing it as cancer that affects the blood and bone marrow characterized by excessive production of immature white blood cells. It defines the main types of leukemia as acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia. The document also outlines the diagnostic evaluation and management of childhood leukemia, including induction therapy, consolidation therapy, maintenance therapy, and stem cell transplantation.
2. Introduction
• Paediatric cancer is rare. Around 60-70%
of paediatric cancer is now curable. In
terms of frequency, leukaemia's (33%)
followed by brain tumours (20%) and
lymphoma (12%) are the 3 cancers
account for paediatric cancers in India.
• Cancer of the hematopoietic system are
disorders that result from the proliferation
of malignant cells originating in the bone
marrow, thymus and lymphatic tissue.
3. LEUKEMIA
• Leukemia is the most common cancer in
children and teens, accounting for almost
1 out of 3 cancers.
4. LEUKEMIA
• Leukemia is a type of cancer that affects the
blood and bone marrow.
• It is characterized by persistent and
enormous production of immature white
cells.
• Definition: It is a disease characterized by
abnormal proliferation and maturation of
bone marrow which can interferes with the
production of normal red cells, white cells,
and platelets.
5. LEUKEMIA
• Incidence:
• In India, annually >10,000 cases of
childhood leukemia have been reported.
ALL accounted for 60 to 85% of all
childhood leukemias. Incidence of
leukemia in Indian pediatric population was
reported as 34%, of which 25% was ALL.
• Most common malignancy in children <15
years. The peak age is 4 years.
• Incidence of male > females (1.3 : 1.0)
• Twice common in white than black children
6. LEUKEMIA
• Causes & Risk factor:
• It is yet unknown in most cases. Factors which
enhance risk are-
• Genetic syndromes/conditions like mongolism,
immunodeficiency, etc
• Exposure to adverse influences
– Ionizing radiations
– Viral particles – EBV, HTL
– Parental smoking
– Therapeutic irradiations
– Chemical & drug exposure
• Familial predisposition
9. IN NORMAL BONE MARROW PLURIPOTENT STEN CELLS
COMMIT TO DIFFERNTIATE ALONG THE MYELOID,
ERYTHOID OR
LYMPHOID PATHWAY IN THE PRESENCE
OF GROWTH FACTOR.
CONTROL MISSING/GENE
MUTATION
NORMAL BONE MARROW REPLACED BYIMMATURE
LEUKOCYTES /BLAST CELLS & THERE IS
UNCONTROLLED PROLIFERATION OF WBC’S.
10. ABNORMAL, IMMATURE LEUKOCYTES THEN
CIRCULATE IN THE BLOOD
THESE IMMATURE BLAST CELLS CROWD THE
BONE MARROW AND IMPAIR THE ABILITY OF THE
BONES TO MAKE HEALTHY BLOOD CELLS.
INFILTERATION TO BONE MARROW LEADS TO
CELLULAR DESTRUCTION AND SUBSEQUENT
COMPETITION FOR METABOLIC ELEMENTS.
INFILTERATION TO ORGANS LIKE SPLEEN, LIVER
& LYMPH GLANDS LEADS TO ENLARGEMENT &
FIBROSIS & RESULT IN C/F
12. TYPES OF LEUKEMIA
• There are several types of leukemia, which are
divided based mainly on whether the leukemia is
acute (fast growing) or chronic (slower growing),
and whether it starts in myeloid cells or lymphoid
cells. Different types of leukemia have different
treatment options and outlooks.
13.
14.
15. Most childhood leukaemia's are acute.
These leukaemia's can progress quickly,
and typically need to be treated right away.
The main types of acute leukemia are:
16. TYPES OF LEUKEMIA
• ACUTE LYMPHOCYTIC LEUKEMIA
• Acute lymphocytic (or lymphoblastic) leukemia is
sometimes called ALL. It starts in the bone
marrow where blood cells are made. It is
more common in children than in adults.
• About 3 out of 4 (80%) childhood leukemias are
ALL. As the name implies, the lymphoid cell line
is affected in this disease.
17. TYPES OF LEUKEMIA
• ACUTE LYMPHOCYTIC LEUKEMIA
• It is a primary disorder of the bone marrow in
which the normal bone marrow elements are
replaced by immature or undifferentiated blast
cells.
• 1 in 2000 live birth
• Age – 3 to 7 years; M > F
18. TYPES OF LEUKEMIA
• ACUTE MYELOID LEUKEMIA (AML):
• This type of leukemia, also called acute
myelogenous leukemia, acute myelocytic
leukemia, or acute non-lymphocytic leukemia,
accounts for most of the remaining cases of
childhood leukemia.
• AML starts from the myeloid cells that normally
form white blood cells (other than lymphocytes),
red blood cells, or platelets.
19.
20. Chronic leukemias are rare in children. These
leukemias tend to grow more slowly than
acute leukemias, but they are also harder to
cure. Chronic leukemias can be divided into 2
main types:
21. TYPES OF LEUKEMIA
• CHRONIC LYMPHOCYTIC LEUKEMIA (CLL):
• Chronic lymphocytic leukemia is a type of
cancer in which the bone marrow makes too
many lymphocytes (functionally incompetent
lymphocytes).
• CLL is a blood and bone marrow disease that
usually gets worse slowly.
• CLL is one of the most common types
of leukemia in adults & accounts for one-third of
all leukemias.
22. TYPES OF LEUKEMIA
• CHRONIC MYELOID LEUKEMIA (CML):
• Chronic myeloid leukemia (CML) is also known
as chronic myelogenous leukemia.
• It's a type of cancer that starts in the blood-
forming cells of the bone marrow and invades
the blood.
• About 15% of leukaemia's in adults are CML.
• CML arises from a mutation in the myeloid stem
cell.
23.
24. Diagnostic Evaluation
• History & symptoms
• CBC & blood chemistry
• Radiological studies
• Bone marrow studies
• Immunological study
• LFT
• LP
25. Management
• Use of chemotherapeutic agents with or
without cranial irradiation in 4 phases
1) Induction therapy
2) Minimal Residual Disease (MRD)
3) Postremission therapy
• Consolidation
• Maintenance
4) CNS prophylactic therapy
• Stem cell transplantation
26. Management
• Induction Therapy
• The goal of induction chemotherapy is to
achieve a remission. This means that
leukemia cells are no longer found in bone
marrow samples, the normal marrow cells
return, and the blood counts become
normal. (A remission is not necessarily a
cure.) More than 95% of children with ALL
enter remission after 1 month of induction
treatment.
27. Management
• Induction Therapy
• These include the chemotherapy drugs L-
asparaginase and vincristine, and a steroid
drug (such as dexamethasone). For
children in high-risk groups, a fourth
chemo drug in the anthracycline class
(most often daunorubicin) is typically
added. Other drugs that may be given
early are methotrexate and/or 6-
mercaptopurine.
28. Management
• Minimal Residual Disease (MRD).
• Even when a complete remission is
achieved, some leukemia cells that cannot
be seen with a microscope may still remain
in the body. The presence of these cells is
referred to as “minimal residual disease
(MRD).” Patients who have achieved
remission after initial treatment for this type
of ALL, but have MRD, are at increased
risk of disease relapse.
29. Management
• Minimal Residual Disease (MRD).
• After a patient achieves a complete
remission, postremission therapy is given.
Blinatumomab (Blincyto®) is approved
(FDA) to treat adults and children who
have B-cell precursor ALL, are in
remission, but still have MRD. Generally, if
blast cells are still evident after the first
course of induction chemotherapy, a
second course of chemotherapy, usually
using different drugs, is given.
30. Management
• Consolidation (intensification) Therapy
• The next, and usually more intense,
consolidation phase of chemo starts once
the leukemia is in remission and typically
lasts for several months. This phase
further reduces the number of leukemia
cells still in the body. Several chemo drugs
are combined to help prevent the
remaining leukemia cells from developing
resistance in higher doses than those
given during the induction phase.
31. Management
• Consolidation (intensification) Therapy
• Some of the drugs used are:
• High-dose methotrexate
• Cytarabine (cytosine arabinoside, ara-C)
• Vincristine
• 6-mercaptopurine
• Blinatumomab
• Inotuzumab ozogamicin
• Cyclophosphamide
• Asparaginase
• Corticosteroids (prednisone, dexamethasone)
32. Management
• Maintenance Therapy
• If the leukemia remains in remission after
induction and consolidation, maintenance
therapy can begin. The goal of
maintenance therapy is to prevent disease
relapse after induction and consolidation
therapy. Most maintenance drugs are
given orally and, typically, patients are
treated in an outpatient setting. They
receive lower doses of chemotherapy
drugs.
34. Management
• CNS prophylactic therapy
• Cranial irradiation is usually given to most children
with ALL during the induction phase, the
consolidation phase and the maintenance phase.
– Intrathecal chemotherapy. Methotrexate,
cytarabine and corticosteroids (prednisone,
dexamethasone).
– High-dose systemic chemotherapy. These drugs
may include methotrexate, cytarabine, 6-
mercaptopurine and asparaginase.
– Cranial irradiation. Radiation therapy to the brain.
35. Management
• STEM CELL TRANSPLANTATION
• The goal of stem cell transplantation is to cure the
patient’s cancer by destroying the cancer cells in
the bone marrow with high doses
of chemotherapy and then replacing them with new,
healthy blood-forming stem cells.
– Allogeneic—patients receive stem cells from a
matched or a partially mismatched related donor
or an unrelated donor.
– Autologous—patients receive their own stem
cells.