What are the risk factors for Acute Lymphoblastic Leukemia (ALL)?

From the Guidelines

Risk factors for Acute Lymphoblastic Leukemia (ALL) include older age, exposure to chemotherapy or radiation therapy, and genetic disorders, particularly Down syndrome, as well as other genetic conditions such as neurofibromatosis, Klinefelter syndrome, Fanconi anemia, Shwachman-Diamond syndrome, Bloom syndrome, and ataxia telangiectasia 1. The most recent and highest quality study, published in 2024, provides an overview of the disease, including its incidence rate and median age at diagnosis, but does not specifically focus on risk factors 1. However, based on the available evidence, it is clear that both genetic and environmental factors contribute to the development of ALL. Some key points to consider include:

• Genetic conditions that increase risk, such as Down syndrome, Bloom syndrome, ataxia telangiectasia, and Fanconi anemia 1
• Environmental exposures, such as radiation and certain chemotherapy drugs, which may contribute to ALL development 1
• The importance of considering the patient's age, with children between ages 2-5 years having the highest risk, and males slightly more affected than females 1
• The role of previous cancer treatment with certain chemotherapy agents, which increases the risk of developing treatment-related ALL 1 It is essential to note that while these risk factors have been identified, most people who develop ALL have no identifiable risk factors, suggesting that random genetic mutations likely play a significant role in the disease's development. Additionally, other studies, such as the one published in 2020, focus on pediatric ALL and discuss risk stratification and treatment approaches, but do not provide new information on risk factors 1. Therefore, the most accurate and up-to-date information on risk factors for ALL is provided by the 2017 study 1.

From the Research

Risk Factors for Acute Lymphoblastic Leukemia (ALL)

The risk factors for Acute Lymphoblastic Leukemia (ALL) can be categorized into several groups, including:

• Genetic risk factors:
  • Presence of Down syndrome 2
  • Inherited genetic variants 3
• Environmental risk factors:
  • Ionizing radiation 4
  • Non-ionizing radiation 4
  • Hydrocarbons 4
  • Pesticides 4
  • Alcohol use 4
  • Cigarette smoking 4
  • Illicit drug use 4
• Infectious risk factors:
  • No specific infectious agents have been consistently linked to ALL, but epidemiologic studies have examined possible infectious risk factors 4
• Demographic risk factors:
  • Age: older age is associated with worse outcomes in adults with ALL 5
  • White blood cell count: elevated leukocyte or absolute peripheral blast counts are associated with worse remission durations 5
• Other risk factors:
  • Maternal reproductive history and birth characteristics 4
  • L2 or L3 morphology 5
  • Myeloid markers on leukemic cells 5
  • Philadelphia chromosome (Ph)-positive or B-cell ALL 5

High-Risk ALL

High-risk ALL is associated with several factors, including:

• Older age 5
• Presence of hypoalbuminemia or hyperbilirubinemia 5
• L2 or L3 morphology 5
• Myeloid markers on leukemic cells 5
• Philadelphia chromosome (Ph)-positive or B-cell ALL 5
• Elevated leukocyte or absolute peripheral blast counts 5

Genetic Basis of ALL

Recent studies have made significant advances in understanding the genetic basis of ALL, including:

• Somatic structural DNA rearrangements and sequence mutations that perturb lymphoid development, cytokine receptors, kinase and Ras signaling, tumor suppression, and chromatin modification 3
• Inherited genetic variants that contribute to leukemogenesis 3
• Clonal evolution and relapse 3