Clinical trial NCT00106015: Diamond Blackfan Anemia Registry (DBAR)
Official title: Diamond Blackfan Anemia Registry (DBAR)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Anemia
Blood Disease
Keywords: inherited pure red cell aplasia
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2005-03-21
Enrollment: 900
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All subjects diagnosed with Diamond Blackfan anemia

Brief summary: The purpose of this study is to maintain a comprehensive registry of patients with the rare inherited bone marrow failure syndrome Diamond Blackfan anemia (DBA).

Detailed description: BACKGROUND:

Diamond Blackfan anemia (DBA) is a heterogeneous genetic disorder characterized by pure red cell aplasia, congenital anomalies, a predisposition to pancytopenia and myelodysplasia as well as hematopoietic and non-hematopoietic cancer. Anemia usually presents in infancy or early childhood and greater than 40% of patients have at least one congenital anomaly. The actuarial cancer risk is, as of yet, undetermined. One DBA gene has been cloned and the existence of at least two other DBA genes has been inferred by linkage analysis. Penetrance and expressivity of DBA genes are highly variable. "Affected" individuals within the same family may vary dramatically as to the degree of anemia, response to corticosteroids, the presence of congenital anomalies and the development of cancer. Despite improvements in understanding of this disorder there are significant deficiencies in knowledge that inhibit the exploitation of this syndrome to increase both specific and general knowledge of mechanisms of hematopoietic failure, birth defects and cancer predisposition. Furthermore this disease will, in the near future, provide a valuable platform to study complex gene interactions. There are less than 1000 individuals in the United States and Canada estimated to have DBA, representing at least 11 genotypes. Thus, no single center follows sufficient numbers of well-characterized patients for meaningful clinical and laboratory investigations. Furthermore, clinicians require an accurate knowledge of the clinical and laboratory presentation, mode of inheritance, treatment response, outcomes and prognosis to make important diagnostic treatment and reproductive decisions. A comprehensive registry that captures this information and characterizes patients accurately is therefore essential to advance our understanding of DBA, and in the process, knowledge regarding hematopoietic cell differentiation, birth defects and cancer predisposition. The registry will be an essential component of clinical and laboratory DBA related research and patient care.

The Diamond Blackfan Anemia Registry (DBAR) was established in 1992, and families were asked to participate if a member was affected by the disorder. From this, the Diamond Blackfan Anemia Foundation (DBAF) was established, largely as a cooperating entity for families to share information. The registry attempts to establish contact with all affected individuals at the time of diagnosis, avoiding the pitfalls of reporting bias inherent to the study of many diseases for which extraordinary events prompt referral to specialized centers. The registry is already capturing a high percentage of the estimated number of new cases per year, and has facilitated genetic studies to define the gene(s) responsible for the disorder. Thus, the registry has an established track record based on funding from non-NIH sources.

The study is in response to RFA HL-04-008 on Molecular Mechanisms Underlying Diamond-Blackfan Anemia and Other Congenital Bone Marrow Failure Syndromes.

DESIGN NARRATIVE:

The objective of this study is to expand and update the DBAR in order to: 1) facilitate investigations into the epidemiology and biology of Diamond Blackfan anemia; 2) provide an accurate phenotype of DBA patients to facilitate genotype- phenotype correlations; 3) provide access of well characterized patients to treatment protocols; 4) provide patients to access to research studies; 5) provide patients with results of research studies; 6) serve as a resource to patients and their doctors to guide diagnostic, therapeutic, and reproductive decisions.

Eligibility criteria: Inclusion Criteria:

* Patients must meet the diagnostic criteria for DBA which include the following:

  1. Normochromic, usually macrocytic and occasionally normocytic anemia developing early in childhood
  2. Reticulocytopenia
  3. Normocellular bone marrow with a selective deficiency of red cell precursors
  4. Normal or slightly decreased leukocyte count
  5. Normal or often increased platelet count
  6. Or, a confirmed mutation in one of the identified DBA genes

Exclusion Criteria:

* Any subject identified as having another bone marrow failure syndrome (eg. Fanconi anemia, dyskeratosis congenita, Shwachman Diamond syndrome, etc.) will be excluded.

Primary outcomes:
measure: Understanding the epidemiology and biology of Diamond Blackfan anemia
timeFrame: yearly
Secondary outcomes:
Other outcomes:
Locations:
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of NY
state: New York
Study officials:
affiliation: Cohen Children's Medical Center of NY/Feinstein Institutute for Medical Research
name: Adrianna Vlachos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cohen Children's Medical Center of NY/Feinstein Institute for Medical Research
name: Jeffrey M Lipton, MD, PhD
role: STUDY_CHAIR
References:
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citation: Lipton JM, Atsidaftos E, Zyskind I, Vlachos A. Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: an update from the Diamond Blackfan Anemia Registry. Pediatr Blood Cancer. 2006 May 1;46(5):558-64. doi: 10.1002/pbc.20642.
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citation: Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec;83(6):769-80. doi: 10.1016/j.ajhg.2008.11.004.
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citation: Lipton JM, Molmenti CLS, Hussain M, Desai P, Florento M, Atsidaftos E, Vlachos A. Colorectal cancer screening and surveillance strategy for patients with Diamond Blackfan anemia: Preliminary recommendations from the Diamond Blackfan Anemia Registry. Pediatr Blood Cancer. 2021 Aug;68(8):e28984. doi: 10.1002/pbc.28984. Epub 2021 Jun 5.
citation: Lipton JM, Molmenti CLS, Desai P, Lipton A, Ellis SR, Vlachos A. Early Onset Colorectal Cancer: An Emerging Cancer Risk in Patients with Diamond Blackfan Anemia. Genes (Basel). 2021 Dec 26;13(1):56. doi: 10.3390/genes13010056.