This document discusses common childhood cancers, focusing on leukemias. It provides details on the types and subtypes of leukemia, risk factors, clinical presentation, evaluation, and management. The main types discussed are acute lymphoblastic leukemia (ALL), which is the most common childhood cancer, and acute myeloid leukemia (AML). The management of ALL involves induction therapy to achieve remission, CNS prophylaxis to prevent spread to the brain, intensification therapy, and maintenance therapy to prevent relapse.

1. CHILDHOOD MALIGNANCIES
PEDRIATICS

2. INTRODUCTION
• Common childhood malignancies include leukemias (30-40%), brain tumors (20%) and lymphoma
(12%) followed by neuroblastoma, retinoblastoma and tumors arising from soft tissues, bones and
gonads.

3. LEUKEMIA
• Leukemia is a malignancy that arises from clonal proliferation of abnormal hematopoietic cells
leading to disruption of normal marrow function leading to marrow failure.
• The clinical manifestations of leukemia are the result of the unregulated proliferation of the
malignant clone and bone marrow failure.
• Leukemia is the most common cancer in children.
• There are two main subtypes, the commoner acute lymphoblastic leukemia (ALL) and acute myeloid
leukemia (AML).
• A small proportion may have chronic myeloid leukemia (CML) and juvenile myelomonocytic
leukemia (JMML).

4. ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) _
• ALL is the most common childhood malignancy accounting for one-fourth of all childhood cancers and
three-fourths of all newly diagnosed patients with acute leukemia.
• Its incidence is approximately 3-4 cases per 100,000 children below 15 yr. of age.
• There is a peak in the incidence of childhood ALL, between the ages of 2 and 5 yr., due to ALL
associated with a pre-B lineage (referred to as common ALL).
• Boys have higher rates than girls, especially in adolescents with T cell ALL.

5. RISK FACTORS FOR CHILDHOOD LEUKEMIA
• Can be either genetic or environmental.
• The genetic risk factors are Down syndrome, Fanconi anemia, Shwachman-Diamond syndrome, Bloom
syndrome, Ataxia telangiectasia, Diamond-Blackfan anemia, Kostmann syndrome, Li-Fraumeni
syndrome, Severe combined immune deficiency, Paroxysmal nocturnal hemoglobinuria,
Neurofibromatosis type 1.
• The environmental includes Ionizing radiation, Alkylating agents (cyclophosphamide, ifosfamide,
carboplatin, procarbazine), Epipodophyllotoxins (etoposide, tenoposide), Nitrosourea (nitrogen
mustard), Benzene.

6. CLINICAL PRESENTATION
• The duration of symptoms in a child with ALL may vary from days to weeks and in some cases few
months.
• The clinical features of ALL are attributed to bone marrow infiltration with leukemic cells (bone marrow
failure) and extramedullary involvement.

7. CONTINUED
• Anemia
• Bleeding
• Infections
• Weight loss
• Bone pain

8. • Hepatomegaly and splenomegaly
• Elevated uric acid levels
• Neurologic manifestations

9. ANAEMIA
• Due to reduced stem cell input or ineffective erythropoiesis or both.
• Lab shows decreased relative proportion of erythroblasts to total count
• Usually the first symptom in AL but mild without symptoms in CL
• Manifests as pallor and fatigue.

10. BLEEDING
• Results from reduced megakaryocytes causing thrombocytopenia
• Manifests as purpura, petechiae, ecchymosis, haemorrhage.
• Bleeding more common in AL than CL

11. INFECTIONS
• Results from granulocytopenia or immune deficiency due to chemotherapy, corticosteroids and disease
process.
• Occurs in the oral cavity, throat, lower colon, urinary tract, lungs , skin.
• Manifests as fever and chills.

12. WEIGHT LOSS
• Attributed to pain, depression, chemotherapy excess production of TNF- alpha.

13. BONE PAIN
• Due to bone infiltration by leukemic cells stretching the periosteum or due to intramedullary infection.

14. LIVER, SPLEEN AND LYMPH NODE ENLARGEMENT
• Manifests with abdominal pain, tenderness, altered LFTs
• Due to leukemic cell infiltration
• Lymphadenopathy is the most common finding in CL

15. ELEVATED URIC ACID LEVEL
• Normal excretion of uric acid is 300-500mg/dl.
• In leukaemia this can be increased by 50X or more.
• Occurs due to catabolism of protein and nucleic acid.
• Urate precipitation may occur due to dehydration.

16. NEUROLOGIC MANIFESTATIONS
• Headache, vomiting, facial palsy, blurred vision, auditory disturbances.
• Due to leukemic cell infiltration or cerebral bleeding.

17. RESPIRATORY MANIFESTATION
• Tachypnea and respiratory distress may be present secondary to severe anemia leading to
congestive heart failure or secondary to the presence of mediastinal mass leading to tracheal
compression (superior mediastinal syndrome).

18. EVALUATION OF A CHILD WITH SUSPECTED
LEUKEMIA
• History and physical examination.
• Complete blood count and differential count.
• Peripheral smear examination (morphology of cells and blasts; blast count; platelet count;
immunohistochemistry; immunophenotype).
• Chest X-ray (include lateral view if mediastinal mass present).
• Electrolytes, urea, creatinine uric acid, LDH, calcium, phosphate, bilirubin, SGOT and SGPT
• Coagulation profile
• Bone marrow aspirate: Morphology, immunophenotype, cytogenetics and FISH
• Bone marrow biopsy
• CSF cytology ( diagnostic and to administer the first intrathecal dose of methotrexate)

19. MANAGEMENT
• The treatment of ALL requires the control of bone marrow or systemic disease, as well as
treatment (or prevention) of extramedullary disease in sanctuary sites, particularly the central nervous
system.
• The treatment on ALL is divided into 4 stages:
(i) induction therapy (to attain remission),
(ii) CNS prophylaxis or CNS preventive therapy,
(iii) intensification ( consolidation) and
(iv) maintenance therapy (continuation).

20. INDUCTION THERAPY
• The goal of this phase is to eradicate leukemia from the bone marrow such that at end of this phase
there are <5% leukemic blasts in bone the bone marrow by morphology.
• Patients who achieve rapid early remission ( <5% blasts in bone marrow) by day 7 or 14 of induction
have a better prognosis than slow responders. Failure to achieve this at end of induction is associated
with high-risk of relapse.
• Induction therapy generally consists of 4 weeks of therapy.
• The drug regimen combining vincristine and prednisone induces remission in 80-95% patients with ALL.
• Since the remission rate and duration are improved by the addition of a third and fourth drug (L-
asparaginase and/ or anthracycline), current induction regimens include vincristine, prednisone, L-
asparaginase and an anthracycline, with remission achieved in 95-98% of cases. The induction therapy
lasts for 4-6 weeks.

21. CNS PREVENTIVE THERAPY
• Most children with leukemia have subclinical CNS involvement at the time of diagnosis and this acts as a
sanctuary site where leukemic cells are protected from systemic chemotherapy because of the blood
brain barrier.
• The early institution of CNS prophylaxis is essential to eradicate leukemic cells which have passed the
blood brain barrier.
• CNS prophylaxis has enabled increased survival rates in leukemia.
• Most children in the past received a combination of intrathecal methotrexate and cranial irradiation.

22. INTENSIFICATION (CONSOLIDATION) THERAPY
• This is a period of intensified treatment administered shortly after remission induction with
administration of new chemotherapeutic agents to tackle the problem of drug resistance.
• There is clear evidence that intensification has improved the long term survival in patients with ALL,
especially those with high-risk disease.
• Commonly used agents for intensification therapy include high dose methotrexate, L-asparaginase,
epipodophyllotoxin, cyclophosphamide and cytarabine.

23. MAINTENANCE (CONTINUATION) THERAPY
• It has been estimated that approximately two to three logs of leukemic blasts are killed during the
induction therapy, leaving a leukemic cell burden in the range of 10 9 -10 10 .
• Additional therapy is therefore necessary to prevent a relapse.
• Once remission is achieved, maintenance therapy is continued for an additional 2-2.5 yr.
• Without such therapy, patients of ALL relapse within the next 2-4 months.
• A number of drug combination and schedules are used, some based on periodic reinduction, others on
continued delivery of effective drugs.
• The main agents used include 6-mercaptopurine daily and methotrexate once a week given orally, with
or without pulses of vincristine and prednisone or other cytostatic drugs.

24. ACUTE MYELOID LEUKEMIA
• Acute myeloid leukemia (AML) also termed as acute non lymphoblastic leukemia, accounts for 15-20%
of leukemia in children.
• AML is a more complex and resistant disease than ALL and results from clonal proliferation of
hematopoietic precursors of myeloid, erythroid and megakaryocytic lineage.

25. CLASSIFICATION OF AML
• AML is divided into several subgroups according to the FAB classification:
• M0 undifferentiated, M1 acute myeloblastic leukemia with minimal maturation, M2 acute myeloblastic
leukemia with maturation, M3 acute promyelocytic leukemia, M4 acute myelomonocytic leukemia, M5
acute monoblastic leukemia, M6 erythroblastic leukemia, M7 acute megakaryoblastic leukemia.

26. LYMPHOMAS
• The lymphomas, a group of neoplastic diseases that arise from the lymphoid and hematopoietic
systems, are divided into Hodgkin disease and NHL.

27. HODGKIN DISEASE
• Hodgkin lymphoma, a lymphoreticular neoplasm primarily of B cell lineage involving lymph nodes and
the lymphatic system has unique molecular, histologic, immune phenotypic and clinical features.
• The malignancy originates in the lymphoid system and primarily involves the lymph nodes.
• It predictably metastasizes to non-nodal or extra lymphatic sites, especially the spleen, liver, bone
marrow, lungs, and mediastinum (i.e., mass of tissues and organs separating the lungs, including the
heart and its vessels, trachea, esophagus, thymus, and lymph nodes), although no tissue is exempt from
involvement.
• It is classified according to four histologic types:
(1) lymphocytic predominance, (2) nodular sclerosis, (3) mixed cellularity, and (4) lymphocytic depletion.

28. MODIFIED ANN ARBOR STAGING FOR HODGKIN
LYMPHOMA
• Stage I: Lesions are limited to one lymph node area or only one additional extra lymphatic site (I-E),such
as the liver, lungs, kidney, or intestines.
• Stage II: Two or more lymph node regions on the same side of the diaphragm or one additional extra
lymphatic site or organ (II-E) on the same side of the diaphragm is involved.
• Stage III: Lymph node regions on both sides of the diaphragm and has spread to one extra lymphatic
site (III-E), spleen (III-S), or both (III-SE).
• Stage IV: Cancer has metastasized diffusely throughout the body to one or more extra lymphatic sites
with or without involvement of associated lymph nodes.

29. STAGING
• Each stage is further subdivided into A, B, E, or S. Stage A denotes absence of associated general
symptoms.
• Stage B indicates presence of symptoms, such as night sweats, fever (100.4° F [38° C]), or weight loss of
10% or more during the preceding 6 months.
• Stage E represents extra lymphatic disease beyond the contiguous nodal disease.
• Stage S is used when the disease involves the spleen.
• Subtype B has a significantly poorer prognosis than others

30. DIAGNOSTIC EVALUATION IN HODGKIN LYMPHOMA
• Physical examination with measurement of lymph nodes.
• Complete hemogram with ESR, C reactive protein.
• Liver and renal functions tests, alkaline phosphatase Lactate dehydrogenase.
• Chest X-ray, mediastinal mass to thoracic cavity ratio.
• CT scan of neck, chest and abdomen.
• Bone marrow biopsy (all children except stages IA/IIA).
• Biopsy from lymph node or involved extranodal site.

31. • Bone scan (if bone pain or raised serum alkaline phosphatase)
• CT scan brain (if indicated)
• Cerebrospinal fluid examination (if indicated)
• PET-CT scan (higher sensitivity for stage and residual mass than conventional imaging)
• Surgical staging with lymph node sampling and lymphangiography (selected cases)

32. CLINICAL MANIFESTATIONS
• painless cervical or supraclavicular lymphadenopathy; the nodes are firm and rubbery in consistency.
• Enlargement of axillary and inguinal lymph nodes is less frequent.
• Other signs and symptoms depend on the extent and location of involvement.
• Mediastinal lymphadenopathy may cause a persistent, nonproductive cough.
• Enlarged retroperitoneal nodes may produce unexplained abdominal pain.
• Systemic symptoms include low-grade or intermittent fever (Pel-Ebstein disease), anorexia, nausea,
weight loss, night sweats, and pruritus.

33. THERAPEUTIC MANAGEMENT
• The primary modalities of therapy are chemotherapy and irradiation.
• Radiation may entail involved field radiation, extended field radiation (involved areas plus adjacent nodes), or
total nodal irradiation (the entire axial lymph node system), depending on the extent of involvement.
• In stage IV disease, chemotherapy is the primary form of treatment, although limited irradiation may be given
to areas of bulky disease.
• Follow-up care of children no longer receiving therapy is essential to identify relapse and second malignancies.
• In children with splenectomy because of laparotomy, prophylactic antibiotics are administered for an
indefinite period.
• Also, immunizations against pneumococci and meningococci are recommended before the splenectomy

34. CLINICAL MANIFESTATIONS AND ASSESSMENT OF
BRAIN TUMORS
• Headache- Recurrent and progressive In frontal or occipital areas, Usually dull and throbbing. Worse on
arising, less during day Intensified by lowering head and straining, such as during bowel movement,
coughing, sneezing.
• Vomiting- With or without nausea or feeding Progressively; more projectile; More severe in morning
upon arising; Relieved by moving about and changing position.
• Neuromuscular Changes-Incoordination or clumsiness; Loss of balance (e.g., use of wide-based stance,
falling, tripping, banging into objects); Poor fine motor control; Weakness; Hyporeflexia or
hyperreflexia; Positive Babinski sign; Spasticity; Paralysis.

35. • Behavioral Changes-Irritability; Decreased appetite; Failure to thrive; Fatigue (frequent naps); Lethargy;
Coma; Bizarre behavior (e.g., staring, automatic movements).
• Cranial Nerve Neuropathy- Cranial nerve involvement varied according to tumor location
• Most common signs:
• Head tilt
• Visual defects (e.g., nystagmus, diplopia, strabismus, episodic “graying out” of vision, visual field defect).
-Vital Sign Disturbances- Decreased pulse and respiration; Increased blood pressure; Decreased pulse
pressure; Hypothermia or hyperthermia.
Other Signs- Seizures; Cranial enlargement*;Tense, bulging fontanel at rest*; Nuchal rigidity; Papilledema
(edema of optic nerve).

36. STAGING OF NEUROBLASTOMA
• Stage I: Localized tumor that is confined to the area of origin capable of complete gross excision;
representative ipsilateral lymph nodes negative for tumor microscopically (nodes that are attached to and
removed with the primary tumor may be positive)
• Stage II-A: Unilateral tumor with incomplete gross resection; representative ipsilateral nonadherent lymph
nodes and contralateral lymph nodes negative for tumor microscopically
• Stage II-B: Unilateral tumor with or without complete gross excision, with ipsilateral nonadherent lymph
nodes positive for tumor; enlarged contralateral lymph nodes must be negative microscopically
• Stage III: Tumor infiltrating across the midline, with or without regional lymph node involvement; or localized
unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral lymph
node involvement
• Stage IV: Dissemination of tumor to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs
• Stage IV-S: Localized primary tumor (as defined for stage I, II-A, or II-B) with dissemination limited to liver, skin,
or bone marrow but not to bone.

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