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General Leukemia

 

Etiology

The etiology of leukemia remains largely unknown. 

Theory that two separate events are needed:

1) In-utero insult

  • Damage to chromosomes early in life makes the cells susceptible to becoming leukemic

2) Second insult

  • Possible infection
  • Possible environmental exposure (for example radiation or chemical exposure)

Supported by cord blood banking studies which show some ‘pre-leukemic’ changes may be already present at birth.

 

Summary of etiological factors associated with pediatric leukemias:

Etiological Factor

 

 

Hereditary

Down syndrome

  • 2.1% incidence by age 5
  • Increased risk AML or ALL
  • Cure rates higher than general population in AML
  • Cure rates worse for ALL than general population ? Due to treatment related toxicity
  • Modifications now in place for T-21 patients

Neurofibromatosis

type I

200-500 times increased risk of developing myeloid malignancy

  • mainly Juvenile Myelomonocytic Leukemia (JMML)
Fanconi anemia

Autosomal recessive

Increased chromosomal fragility

Defective replication and repair of DNA

Bloom syndrome

Autosomal recessive

Increased chromosomal fragility

Defective replication and repair of DNA

Shwachman Diamond Chronic neutropenia with pancreatic failure
Ataxia-Telangiectasia

Autosomal recessive

Increased chromosomal fragility

Diamond-Blackfan anemia Increased myelodysplasia
Immunodeficiency Syndromes Congenital Immunodeficiency Syndromes

Wiskott-Aldrich syndrome

Congenital Hypogammaglobulinemia

Chronic treatment with immunosuppressive drugs  

Ionizing radiation

Atom bomb

Risk of leukemia dose related:

  • higher dose associated with higher risk.

Type of leukemia depended on age at time of exposure:

  • In children increased risk of ALL
  • In adults increased risk of AML

Toxins

Chemotherapy agents

Nitrogen Mustard

Cyclophosphamide

Ifosfamide

Chlorambucil

Melphalan

Etoposide

  • All associated with secondary AML
Benzene Chronic exposure to Benzene linked with development of AML in adults.
Paternal chemical exposure (insecticides) smoking during preconception period Not strongly linked

Low-frequency Electromagnetic frequencies

Inconclusive

This is not proven.

Infectious agents

Inconclusive - suggested increase with some infections

Maternal exposure to viral infection has sometimes been observed

Maternal Reproductive History

 

Higher risk of ALL in subsequent children if there is a history of fetal loss.

Maternal age   Increased risk of ALL with increased maternal age
Higher fetal birth weight Probably secondary to increased maternal age. Associated with increased risk of ALL

 

 

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