Acute Lymphoblastic Leukemia ALL : Diagnosis,Prognostic Features

4th Pediatric Infectious Diseases Conference

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ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Related topics

Treatment and Work Up For ALL Patients

Relapse Management,Radiation Therapy and Precautions

Dr Ira Shah
M.D, DCH(Gold Medalist), FCPS, DNB
Edited by Dr. Bharat R Agarwal
Consultant Pediatric Hematologist and Oncologist.

Q.What is ALL?

A. ALL is the commonest childhood cancer. The peak age is between 2-6 years. Boys are affected more frequently as compared to girls.

Q. How do you diagnose ALL?

A. On clinical suspicion, a variety of tests are done :- blood tests, bone marrow aspiration & biopsy, monoclonal antibody tests, immunophenotyping etc.

However, primary diagnosis is made by bone marrow examination. By definition, the presence of 30% or more blasts in the marrow is diagnostic of acute leukemia.

The distinction between ALL and AML is made primarily by morphology of blasts in the marrow and the characteristic pattern of staining with cytochemical stains. Morphologically, the lymphoblasts are smaller than the myeloblasts and do not stain with cytochemical stains except with PAS.

Q. What are the prognostic features of ALL?

A. The various clinical and laboratory factors that determine prognosis are as follows: -

Age at diagnosis
Infants with ALL especially young infants of less than 6 months have a high risk of treatment failure. The poor outcome for infants with ALL is strongly associated with the presence of t (4., 11) translocation involving the MLL gene.

Young children (1-9 years) have a favourable outcome as compared to older children or infants.
WBC count at diagnosis
Patients with high WBC counts at diagnosis (> 50,000/ cu mm) have a poorer prognosis.
Gender
Girls have a slightly better prognosis. One reason for better prognosis in girls is the occurrence of testicular relapses among boys. Also boys are at higher risk for bone marrow relapse.
Cellular morphology
In the past, ALL was classified into 3 types - L1, L2 & L3 using the FAB criteria for prognosis. However this classification is no longer applied. However molecular and biologic characteristics are used for determining the outcome.
- Immunophenotype: -
  
  B cell precursor ALL - Represents 80-85% of childhood ALL. Approximately 80% of B-cell precursor ALL express the CALLA, CD 10 antigen. The lack of cALLA is associated with a worse prognosis.
  
  Stage of B cell maturation - Patients with early pre B phenotype have the best prognosis, pre B phenotype have an intermediate prognosis and B-cell type have the worst prognosis.
  
  T-cell ALL - Approximately 15% of children with ALL have a T-cell phenotype. In patients with T-cell ALL, CD2 has a favourable prognosis, whereas CD7 +, CD2- and CD5- immunophenotype has a worse prognosis.
- Chromosome number: -
  
  Hyperdiploidy (> 50 chromosomes per cell or DNA index > 1.16) have favourable prognosis. Hyperdiploid leukemic cells are susceptible to undergoing apoptosis.
  
  Trisomy 4 and 10 are associated with favorable prognosis. Hypodiploidy (<45 chromosomes per cell) have a high risk of treatment failure.
- Chromosomal translocations: - t (8; 14), t (9; 22), t (4; 11) and t (1; 19) are associated with unfavorable prognosis, t (12; 21) has a favourable prognosis.
Rapidity of leukemic cytoreduction following onset of treatment
Patients who have a rapid reduction in the leukemic cells in the bone marrow within 7-14 days following multiagent chemotherapy have a better prognosis.
CNS disease at presentation Patients with CNS manifestations at onset have an unfavourable prognosis.
Mediastinal mass Patients with a mediastinal mass at onset have a favourable prognosis.

CCG divided patients into "standard risk" or "high risk" based on age and WBC criteria. Standard risk patients are patients between 1-9 years and those who have WBC count <50,000 / cu mm at diagnosis. The remaining patients are classified as high-risk ALL. The "very high risk" category includes -presence of t (9; 22); M3 marrow on day 29 or M2 or M3 marrow on day 43; or hypodiploidy (DNA index <0.95). Infants with ALL are considered "high risk" and have special chemotherapy protocols.

Next : Treatment and Work Up For ALL Patients

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