Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Cancer in Inherited Bone Marrow Failure Syndromes

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) Identifier:
First received: November 29, 2001
Last updated: November 11, 2014
Last verified: February 2014


A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Mutations in IBMFS genes are relevant to carcinogenesis in sporadic cancers.

Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.

These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.

Carriers of IBMFS gene mutations are at increased risk of cancer.

The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied.


To determine the types and incidence of specific cancers in patients with an IBMFS.

To investigate the relevance of IBMFS gene mutations in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.

To identify risk factors for IBMFS-related cancers in addition to the primary germline mutations.

To determine the risk of cancer in IBMFS carriers.


North American families with a proband with an IBMFS.

IBMFS suspected by phenotype, confirmed by mutation in an IBMFS gene, or by clinical diagnostic test.

Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result.

Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase.

Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure.

Shwachman-Diamond Syndrome: malabsorption; neutropenia.

Amegakaryocytic thrombocytopenia: early onset thrombocytopenia.

Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia.

Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest.

Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts.

Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia.

First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children.

Grandparents of IBMFS-affected subjects.

Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV).


Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance.

Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS.

Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones..


Fanconi's Anemia
Anemia, Diamond Blackfan
Dyskeratosis Congenital

Study Type: Observational
Official Title: Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 4000
Study Start Date: November 2001
  Show Detailed Description


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
  • Fanconi s anemia.
  • Diamond-Blackfan anemia.
  • Dyskeratosis congenita.
  • Shwachman-Diamond Syndrome.
  • Amegakaryocytic thrombocytopenia.
  • Thrombocytopenia absent radii.
  • Severe congenital neutropenia.
  • Pearson s Syndrome.
  • Other bone marrow failure syndromes.
  • First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children.
  • Grandparents of IBMFS-affected subjects, specifically for Hypothesis 4.
  • Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors for those tumors (e.g. smoking, drinking, HPV).
  • Adult patients and family members who are unable to provide consent.


Eligibility for this amendment will be assessed only after the subject has been deemed eligible for the parent protocol.

Specific eligibility for the proposed amendment are as follows:

  • Ability to read, write, and speak in English.
  • Between the ages of 11 & 21.
  • Informant has at least one biologically related, living sibling (full or half) who has an IBMFS.


  • Evidence that the hematologic disorder is acquired rather than genetic. Such evidence includes temporal relation of the aplastic anemia to known marrow suppressant drugs, chemicals, toxins, or viruses (in the absence of evidence indicative of an inherited marrow failure disorder).
  • Known causes of cytopenias such as autoantibodies to red cells, platelets, or neutrophils, viruses (especially hepatitis), micronutrient deficiencies, transient erythroblastopenia of childhood, and cyclic neutropenia.
  • Assignment of the patient s physical findings to other syndromes or causes that are not part of the IBMFS disease spectrum.
  • Inability or unwillingness to complete the questionnaires or permit access to medical records and pathology specimens.
  • There are no other exclusion parameters not related to the primary disease.


  • Diagnosis of an IBMFS or any other chronic illness.
  • Cognitive impairment or inability to express feelings or experiences verbally or inability to provide informed consent.
  • Emotional distress at the time of the interview.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00027274

Contact: Blanche P Alter, M.D. (240) 276-7239

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Principal Investigator: Blanche P Alter, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) Identifier: NCT00027274     History of Changes
Obsolete Identifiers: NCT00056121
Other Study ID Numbers: 020052, 02-C-0052
Study First Received: November 29, 2001
Last Updated: November 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Fanconi's Anemia
Aplastic Anemia
Diamond Blackfan Anemia
Dyskeratosis Congenita
Shwachman-Diamond Syndrome
Familial Cancer
Inherited Bone Marrow Failure
Bone Marrow
Inherited Bone Marrow Failure Syndromes

Additional relevant MeSH terms:
Anemia, Diamond-Blackfan
Dyskeratosis Congenita
Fanconi Anemia
Fanconi Syndrome
Hemoglobinuria, Paroxysmal
Anemia, Aplastic
Anemia, Hemolytic
Anemia, Hypoplastic, Congenital
Blood Platelet Disorders
Bone Marrow Diseases
Congenital Abnormalities
DNA Repair-Deficiency Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Kidney Diseases
Leukocyte Disorders
Metabolic Diseases
Metabolism, Inborn Errors
Myelodysplastic Syndromes
Pathologic Processes
Red-Cell Aplasia, Pure processed this record on November 25, 2014