Colorectal cancer screening and surveillance strategy for patients with Diamond Blackfan anemia: Preliminary recommendations from the Diamond Blackfan Anemia Registry

Lipton, Jeffrey M.; Molmenti, Christine L. Sardo; Hussain, Maryam; Desai, Pooja; Florento, Maria; Atsidaftos, Eva; Vlachos, Adrianna

doi:10.1002/pbc.28984

Cited by 9 publications

(3 citation statements)

References 21 publications

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“…The solid tumors with the greatest statistical risk, with more than a single case, were CRC and OS, with O/E of 45 and 42 respectively [ 13 ]. Five years later (DBAR median age 23.6 years for 813 patients), an update reported 51 patients with 60 cancers (10 post-HSCT and 7 basal or squamous cell skin cancers) with a median age of 33 years confirming and refining the earlier results ( Table 1 and Table 2 ) [ 31 ]. The leading diagnoses remained the same, now with 11 predominantly early onset colorectal cancers (EOCRC; median age 41 years, range 20–51 years, 2 post-HSCT) and 7 cases of OS (median age 11 years, range 4–34 years, 3 post-HSCT).…”

Section: Introductionsupporting

confidence: 57%

“…The Diamond Blackfan Anemia Registry of North America (DBAR; (accessed on 23 December 2021), #NCT00106015) was established in 1991 and is the largest international DBA patient cohort with ongoing follow up. Three important studies from the DBAR defining the cancer risk and proposing a preliminary screening and surveillance strategy were published from 2012–2021 [ 12 , 13 , 31 ]. In 2018, Vlachos et al [ 13 ] refined their 2012 study [ 12 ] using the DBAR cohort of 702 patients, median age 18 years, with 12,376 patient-years enrolled from 1991–2016.…”

Section: Introductionmentioning

confidence: 99%

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Early Onset Colorectal Cancer: An Emerging Cancer Risk in Patients with Diamond Blackfan Anemia

Lipton

Molmenti

Desai

et al. 2021

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Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome, the founding member of a class of disorders known as ribosomopathies. Most cases result from loss of function mutations or deletions in 1 of 23 genes encoding either a small or large subunit-associated ribosomal protein (RP), resulting in RP haploinsufficiency. DBA is characterized by red cell hypoplasia or aplasia, poor linear growth and congenital anomalies. Small case series and case reports demonstrate DBA to be a cancer predisposition syndrome. Recent analyses from the Diamond Blackfan Anemia Registry of North America (DBAR) have quantified the cancer risk in DBA. These studies reveal the most prevalent solid tumor, presenting in young adults and in children and adolescents, to be colorectal cancer (CRC) and osteogenic sarcoma, respectively. Of concern is that these cancers are typically detected at an advanced stage in patients who, because of their constitutional bone marrow failure, may not tolerate full-dose chemotherapy. Thus, the inability to provide optimal therapy contributes to poor outcomes. CRC screening in individuals over the age of 50 years, and now 45 years, has led to early detection and significant improvements in outcomes for non-DBA patients with CRC. These screening and surveillance strategies have been adapted to detect familial early onset CRC. With the recognition of DBA as a moderately penetrant cancer risk syndrome a rational screening and surveillance strategy will be implemented. The downstream molecular events, resulting from RP haploinsufficiency and leading to cancer, are the subject of significant scientific inquiry.

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Section: Introductionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Early Onset Colorectal Cancer: An Emerging Cancer Risk in Patients with Diamond Blackfan Anemia

Lipton

Molmenti

Desai

et al. 2021

Genes

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“…DBA has recently been classified as a cancer predisposition syndrome of moderate penetrance, in which patients have a 4.8-fold higher relative risk of developing cancer ( Lipton et al, 2021b ). Colorectal cancer and osteogenic sarcoma are the most prevalent solid tumors in patients with DBA, and the Diamond Blackfan Anemia Registry (DBAR) has recently released early screening guidelines for CRC ( Lipton et al, 2021b ). At the present time, the median age for developing CRC in the setting of DBA is 41 years, though based on only nine patients ( Lipton et al, 2021a ).…”

Section: Discussionmentioning

confidence: 99%

Variable Clinical Features in a Large Family With Diamond Blackfan Anemia Caused by a Pathogenic Missense Mutation in RPS19

et al. 2022

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Introduction:Diamond Blackfan anemia (DBA) is an autosomal dominant ribosomopathy caused predominantly by pathogenic germline variants in ribosomal protein genes. It is characterized by failure of red blood cell production, and common features include congenital malformations and cancer predisposition. Mainstays of treatment are corticosteroids, red blood cell transfusions, and hematologic stem cell transplantation (HSCT). Despite a better understanding of the genotype of DBA, the biological mechanism resulting in the clinical phenotype remains poorly understood, and wide heterogeneity can be seen even within a single family as depicted here.Case Description:Thirty family members enrolled in the National Cancer Institute inherited bone marrow failure syndromes study were evaluated with detailed medical questionnaires and physical examinations, including 22 in the family bloodline and eight unrelated partners. Eight participants had been previously told they had DBA by clinical criteria. Targeted germlineRPS19testing was done on all family members. A pathogenic heterozygous missense mutation inRPS19(p.R62Q, c.185G > A) was detected in ten family members, including one person previously presumed unaffected. Eight family members presented with macrocytic anemia in infancy; all of whom were responsive to prednisone. Four family members became treatment independent; however, one individual became transfusion-dependent 36 years later following an episode of pneumonia. One prednisone responsive individual electively discontinued steroid treatment, and lives with severe anemia. One prednisone responsive individual died at age 28 from a stroke. Two family members developed colorectal cancer in their fifties; one had never required treatment for anemia. None had major congenital anomalies.Discussion:This large family with DBA demonstrates the heterogeneity of phenotypes that can be seen within the same genotype. Most family members presented with steroid-responsive anemia in infancy and subtle congenital malformations, findings consistent with recent genotype-phenotype studies ofRPSDBA. However, two family members were relatively unaffected, underscoring the importance of further studies to assess modifier genes, and epigenetic and/or environmental factors which may result in normal erythropoiesis despite underlying ribosome dysfunction. This large, multigenerational family highlights the need for individualized treatment, the importance of early cancer surveillance even in individuals with clinically mild phenotypes, and the benefit of long-term follow-up to identify late complications.

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The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia

et al. 2022

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Colorectal cancer screening and surveillance strategy for patients with Diamond Blackfan anemia: Preliminary recommendations from the Diamond Blackfan Anemia Registry

Cited by 9 publications

References 21 publications

Early Onset Colorectal Cancer: An Emerging Cancer Risk in Patients with Diamond Blackfan Anemia

Early Onset Colorectal Cancer: An Emerging Cancer Risk in Patients with Diamond Blackfan Anemia

Variable Clinical Features in a Large Family With Diamond Blackfan Anemia Caused by a Pathogenic Missense Mutation in RPS19

The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia

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