Leukemia & Lymphoma

CHILDHOOD LEUKEMIAS • • •

The most common childhood cancers (33%). It represents a clonal expansion & arrest at a specific stage of normal myeloid & lymphoid hematopoiesis. Types:

o Acute (97%): 1. 2. 3. 4.

Lymphoblastic (ALL) 75%. Myeloid (AML) 20%. Undifferentiated (AUL) <0.5%. Mixed lineage (AMLL).

o Chronic (3%):

1. Myeloid. 2. Lymphoblastic (very rare in pediatrics).

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ACUTE LYMPHOBLASTIC LEUKEMIA

LYMPHOMA

DEFINITION

• Abnormal growth & proliferation of immature lymphocytes (lymphoblasts) within the BM.

EPIDEMIOLOGY

• The most common childhood cancer • The third most common childhood (25%). cancer (20%) after leukemias (33%) & brain tumors (25%). • 75% of childhood leukemias. • 2-10 years (10% in infants < 1 year). • 5-15 years (for NHL). • M:F ratio is 2:1 (with exception of • Males are more affected than infant leukemia where there is a females. female predominance. • Higher incidence among middle & high socio-economic classes. • Highest incidence in Egypt & USA • Higher incidence in blacks than (whites). whites (difference in susceptibility or environmental exposure). • Intermediate in most European countries. • Lowest in UAS (blacks), India & Kuwait.

AGE “Peak inc.” SEX SOCIAL DIST. GEOGRAPHIC DIST.

• Abnormal growth & proliferation of mature lymphocytes within the lymphatic system which includes LNs, spleen, thymus, tonsils & BM.

ETIOLOGY Unknown but may be due to many factors: Evidences are: Evidences are: Genetic factors • Higher incidence among: • Higher incidence among: 1. Siblings of affected children. 1. … 2. Children with down syndrome. 3. Monozygotic twins. • Occurrence of familial leukemia. • Occurrence of familial lymphoma. As: As: Viral infection 1. EBV in ALL (L3). 1. EBV. 2. Endemic burkitt’s lymphoma, Human 2. Human T lymphocytic viruses. T lymphocytic viruses I & II & 3. HIV. retroviruses in T-cell leukemia. • Exposure to ionizing radiation induces chromosomal aberrations, interferes Environmental with immunologic defenses & predisposes to malignancy (may cause acute factors leukemia). • Chronic exposure to: • Chronic exposure to: Chemical 1. Benzene, herbicides, pesticides. 1. … carcinogens 2. Drugs as chemotherapy & 2. … cholarmphenicol. • Hydantion may be associated with pseudo-lymphomas which resolve • Maternal use of contraceptives, cigarettes & alcohol. when the drug is discontinued. • Children with immune deficiency diseases. Immune have an ↑ risk of … • Patients receiving immunosuppressive drugs. deficiency • Patients with autoimmune diseases & organ transplants. (ALL or lymphoma)

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D.D. 1. AML: o Morphology, immuno-pheno-typing & cytogenetic study of BM aspirate can differentiate. 2. Leukemic phase of lymphoma: o … 3. Aplastic anemia: (due to inhibition of normal hematopoietic progenitors by leukemic cells) o BM biopsy can differentiate. 4. Small round cell tumors: (as neuro-blastoma & retino-blastoma) o May mimic ALL by clinical & laboratory features when infiltrate BM. o Demonstration of the 1ry tumor can differentiate. 5. Some infectious diseases: (as IMN) o May mimic ALL due to fever, lymphadenopathy, HSM, blood cytopenia & atypical lymphocytes. o Morphology of atypical lymphocytes & cytogenetic study of BM aspirate can differentiate. 6. Osteomyelitis & rheumatologic diseases: (due to bone pain & arthralgia)

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PROGNOSTIC FACTORS OF ALL 1. AGE: •

Prognosis is poor when age is < 2 years & > 10 years at diagnosis and worst in infant < 1 year.

2. RACE: Higher relapse rate in boys than girls. 3. RACE: Higher relapse rate in black children due to:

1. Higher incidence of high initial WBCs count, mediastinal mass & L2 morphology. 2. Lower socio-economic status.

4. ONSET OF LEUKEMIA:

•

The slower the onset, the more durable the remission that follows institution of therapy.

5. LEUKEMIC CELL BURDEN: •

Assessed by evaluation of extra-medullary disease as the degree of HSM & lymph-adenopathy.

6. NUTRITIONAL STATUS: •

Malnourished children have less tolerance & receive sub-optimal doses of chemotherapy.

7. CNS INVOLVEMENT: •

CNS infiltration is associated with lower remission induction, higher relapse rate & shorter survival.

8. Hb CONCENTRATION: • •

Hb < 10 gm/dL is associated with higher remission induction, lower relapse rate & longer survival. Normal Hb level is associated with bulky extra-medullary disease & high percentage of blasts.

9. WBCs COUNT: High initial WBCs count is associated with bulky extra-medullary disease & high risk of CNS or testicular relapses.

10. PLATELETS COUNT: • •

Platelets count < 20.000/mm3 is associated with shorter remission. Leukemia associated with petechial hemorrhages may predispose to CNS or testicular relapses.

11. LDH: High LDH level is associate with shorter remission. 12. BLAST MOTPHOLOGY: L1 have more favorable prognosis than L2 - L3 have the worst prognosis. 13. IMMUNOPHENOTYPING:

• o •

B cell have the worst prognosis. Early pre B have more favorable prognosis than pre B - Mature B have extremely poor prognosis. T cell have poor prognosis - Early T have more favorable prognosis than mature T.

14. RESPONSE TO TREATMENT: • •

Failure to reduce leukemic mass rapidly permits the emergence of clones of lymphoblasts resistant to drugs. So early responders with < 5% blasts in BM on day 7 have the best DFS (Disease Free Survival). Esnips.com/user/ma7moud