Patient case: 4-year-old female with leukemia; genetic feature: ABL1

Clinical trial: Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Hematologic Cancer

Summary: Background:
  -  Individuals may be prone to develop blood or lymph node cancers (leukemia or lymphoma) for a variety of reasons, including genetic predisposition to these cancers, environmental exposures or other medical conditions.
  -  Studies of people and families at high risk of cancer often lead to clues about their cause that may also be important regarding the sporadic occurrence of these cancers in the general population.
  -  Identifying genetic or environmental factors that play a role in the development of these diseases may be important in developing prevention trials, screening programs and treatments.
  Objectives:
  -  Describe the cancers and other conditions in families with blood or lymph node cancer.
  -  Find and describe genes that may cause blood and lymph node cancer, and understand how they work in families.
  -  Use laboratory methods to try to determine if it is possible to identify who is at highest risk of blood or lymph node cancer.
  -  Test how genes act with other factors to alter the risk of disease, its severity or its manifestations in families.
  Eligibility:
  -  Individuals of any age with a personal or family history of a blood or lymph node cancer.
  -  Individuals with a personal or family history of medical conditions or environmental exposures that may predispose to blood or lymph node cancer.
  Design:
  -  Participants complete questionnaires about their personal and family medical history and provide consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with blood or lymph node cancer, tumors, or other related illnesses for whom they are the legally authorized representative.
  -  Participants donate a sample of blood or cheek cells, or a lock of hair for genetic studies.
  -  Patients may also be evaluated at the NIH Clinical Center by one or more of the following specialists: cancer doctor or blood specialist, medical geneticist, research nurses or clinical social worker. They may have blood and urine tests and a cheek swab or mouth wash to collect cheek cells. Some patients may also be asked to have x-rays and routine imaging, such as CT scans or ultrasound tests, cell surface markers, skin biopsy, and, with special consents, bone marrow biopsy, MRI or PET scans, apheresis or fluorescein angiography and photography.

Detailed description: Background:
  -  Persons may be prone to develop hematologic or lymphoproliferative cancer for a variety of reasons including: inherited predisposition of benign, premalignant, or malignant conditions; environmental exposures shared by family members; previous tumors or preneoplastic conditions; immune deficiency; or, stochastic processes
  -  Investigations of individuals and families at high risk of cancer often lead to etiologic clues that may be important in the sporadic counterparts of these cancers in the general population
  -  Identification of etiologically important genetic factors could inform chemoprevention trials, screening programs, and treatment of hematologic and lymphoproliferative cancers
  Objectives:
  -  To evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to hematologic cancer
  -  To evaluate potential precursor states of malignancy in families at risk and increase understanding of the factors that cause progression
  -  To quantify the risks of specific tumors in family members and define syndromic constellations
  -  To identify, map, characterize, clone, and determine function of tumor susceptibility genes
  -  To validate and test associations of biomarkers with risk
  -  To identify genetic determinants, environmental factors, and gene-environmental interactions conferring cancer risk in individuals and families
  -  To identify differences and similarities between the familial and sporadic condition
  -  To educate and counsel study participants about their risk of hematologic malignancy including prevention recommendations and early detection activities when known
  -  To develop syndrome specific educational materials for medical professionals and high-risk family members
  Eligibility:
  -  Persons of any age will be considered if
  -  there is a personal or family medical history of hematologic/lymphoproliferative malignancy of an unusual type, pattern, or number; or,
  -  there are known or suspected factor(s) predisposing to hematologic malignancy, either genetic or congenital factors, environmental exposure, or unusual demographic features
  -  For familial neoplasms, two or more living affected cases among family members are generally required
  Design:
  -  This is a prospective study. Families are studied long-term using a cohort approach.
  -  The study design and clinical evaluation vary by the specific type of familial neoplasm being studied
  -  The overall approach to eligible families includes defining affection status, characterization of disease, localization of genetic loci, identification of genes, evaluation of phenotype/genotype correlations, estimation of risk of the disease associated with carrier status, and identification of other risk factors that modify penetrance (genetic, environmental, and host factors)

Eligibility: -  INCLUSION CRITERIA:
  On referral, persons of any age will be considered for inclusion in the study because of either:
  -  A family or personal medical history of hematologic/ lymphoproliferative malignancy of any unusual type, pattern, or number; or,
  -  Known or suspected factor(s) predisposing to hematologic malignancy, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation, diet, infectious agents, etc.), or unusual demographic features (very young age of onset multiple tumors, etc.).
  Personal and family medical history must be verified through questionnaires, interviews, and review of pathology slides and medical records. For familial neoplasms, two or more living affected cases among family members are generally required, although in selected instances exceptions may be made, e.g., for WM, one cases plus a living 1st degree relative with an autoimmune condition will qualify a family for further investigations.
  Familial aggregation of any hematologic cancer(s) is eligible for study, our current active accrual efforts fall into 5 categories
  1. Chronic lymphocytic leukemia (CLL)
  2. Waldenstrom s macroglobulinemia (WM)
  3. Non-Hodgkin s Lymphoma (NHL)
  4. Hodgkin disease (HD)
  5. Mixed hematologic and lymphoproliferative diseases
  EXCLUSION CRITERIA:
  -  Referred individuals for whom reported diagnosis cannot be verified.
  -  Referred individuals who decline informed consent.

Relevance to patient case: not relevant