Abstract
Background: Diamond Blackfan anemia (DBA) syndrome is an inherited bone marrow failure syndrome characterized by red cell aplasia, congenital anomalies and a predisposition to cancer. At the Diamond Blackfan Anemia International Collaboration Conference 2023, a pre-meeting was held with a goal to establish the DBA Syndrome Cancer Consortium (DBASCC). Individual country registries presented their data, including Czech Republic, France, Germany, Greece, Italy, Netherlands, United Kingdom (UK), and United States (US). The analyses are occurring in two phases; Phase 1 describes all the individuals with DBAS who have cancer, and Phase 2 will refine the epidemiology of cancer in DBA syndrome.
Purpose: To collect and delineate the cases of cancer and myelodysplastic syndrome (MDS) in patients with DBA syndrome throughout the countries in the DBASCC and to develop surveillance strategies for certain cancers with assistance from adult cancer experts.
Methods: A survey tool was developed using REDCap (Research Electronic Data Capture). REDCap is a secure web application for building and managing online surveys and databases. REDCap is compliant with various international data privacy regulations including 21 CFR Part 11, FISMA, HIPAA, and GDPR. Each country inputted de-identified patient data into the database. For older registries where reconsent was necessary to share data, aggregate data were collected. Ages of cancer diagnosis are compared using Surveillance, Epidemiology, and End Results (SEER) data in the United States.
Results: There were 2336 patients in 8 countries, including 153 cases of cancer and/or MDS in 133 subjects enrolled in the DBASCC: 118 cancer, 19 MDS, and 16 non-melanoma skin cancer (excluded from analysis). There are 8 subjects from the Czech Republic, 28 from France, 13 from Germany, 3 from Greece, 9 from Italy, 4 from the Netherlands, 6 from the United Kingdom, and 62 from the US. Patients are diagnosed with colorectal carcinoma (n=25), osteosarcoma (21), breast cancer (14), lymphoma (10), acute myelogenous leukemia (AML; 9), gynecologic (7), lung cancer (4), intrahepatic cholangiocarcinoma (3), melanoma (3), testicular cancer (3), thyroid carcinoma (3), esophageal cancer (2), non-skin squamous cell carcinoma (2; one vaginal and one oral), Wilms tumor (2), B-acute lymphoblastic leukemia (1), bladder cancer (1), chronic lymphoblastic leukemia (1), gastric cancer (1), hepatocellular carcinoma (1), multiple myeloma (1), pancreatic cancer (1), retinoblastoma (1), rhabdomyosarcoma (1), and soft tissue sarcoma (1). The median age of first non-skin cancer diagnosis is 33.61 years (range 2.28 – 70 yrs). Skin cancer was also reported – 8 cases of basal cell carcinoma, 6 cases of squamous cell carcinoma, and 2 undefined. The median age for skin cancer is 50.11 years. Skin cancers are not included in the overall analyses. Nineteen subjects were reported to have a diagnosis of MDS. The median age of MDS diagnosis is 24.77 years (range 0.82 – 61.92 yrs). The genotypes of the cancer/MDS subjects are RPS19 (49%), RPL11 (16%), RPL5 (12%), RPL35A (9%), RPS17 (6%), RPS10 (1%), RPS24 (1%), RPL35 (<1%), GATA1 (2%), and HEATR3 (<1%); 32 do not have a known genotype and RPS26 is markedly underrepresented. The genotypes follow the normal distribution seen in the DBAS population, except for the absence of subjects with RPS26 with cancer/MDS (p<0.005). Of the subjects with esophageal/colorectal cancers, the treatment at the time of the cancer diagnosis: 4 were treatment independent, 3 were on steroids, 3 were s/p stem cell transplantation, 6 were transfusion dependent, 1 was receiving transfusions and steroids.
Conclusions: DBA is a significant cancer predisposition syndrome. Combining international registry data provides a more granular and robust analysis of cancer in DBA syndrome. The most common solid tumors continue to be colorectal cancers and osteosarcoma. Colonoscopy is recommended for patients beginning at age 20 years. The number of breast cancer cases, affecting only women, has also increased. Breast cancer screening should therefore be considered. Skin cancer, although not included in SEER, occurs at younger than in the general population, thus may warrant screening as well.
