Description:
Progressive bone marrow failure, myelodysplastic syndrome and acute myeloid leukemia are hematologic complications in patients with inherited bone marrow failure syndromes (IBMFS) and related hematopoietic malignancy predisposition syndromes that are potentially curable with hematopoietic stem cell transplantation (HCT). However, a myriad of age-related and syndrome specific non-hematologic complications can develop over time in transplanted and non-HCT patients with these syndromes and pose unique challenges that can impact the quality and duration of life. Our understanding of the biology of life-threatening non-hematologic complications such as hepatopulmonary syndrome, arterio-venous malformations, pulmonary or liver fibrosis, and their association with age, disease phenotype and HCT in short telomere syndromes [dyskeratosis congenita (DC)/telomere biology disorders (TBD)] is evolving and is integral to inform treatment decisions and management. Another major concern is an inordinately high risk of solid tumors, particularly squamous cell carcinoma of the head and neck and anogenital region in Fanconi anemia (FA) and DC/TBD. This risk increases with age, and cancers tend to develop earlier in patients who have received HCT. This education session will address the non-hematologic complications in short telomere syndrome (DC/TBD), age-associated predisposition to specific cancers in the classic inherited bone marrow failure syndromes and in relation to HCT. The session will also discuss specific pre- and post-HCT considerations to reduce transplant-associated and long-term complications in the IBMFS. Dr. Kristen Schratz will outline the extra hematopoietic manifestations of short telomere syndromes (DC/TBD) in children and adults. She will discuss the natural histories of these complications and their relevance to diagnostic and treatment decisions for patients with bone marrow failure with a particular emphasis on pulmonary, hepatic and immune complications. This talk will also address the indications for telomere length testing beyond hematologic indications.

Dr. Neelam Giri will discuss the non-hematopoietic malignancies in the classic IBMFS and other hematopoietic malignancy predisposition syndromes with special focus on FA and DC and in relation to HCT or no HCT. She will use case-based approach to highlight the implication of biallelic FANCD1/BRCA2 or FANCN/PALB2 mutations and the risks of specific cancers in children versus the risk of squamous cell carcinomas in adults with FA due to mutations in other FA genes.

Dr. Carmen Bonfim will discuss the need for careful pre- and post-transplant considerations that must be given to patients with IBMFS and hematological malignancies predisposition syndromes. Early toxicities and long-term complications may be related to a combination of the underlying disease and exposures to pre, peri and post transplantation risk factors. Maintaining a high index of suspicion for these late effects is essential for the development of more effective surveillance strategies and prevention of sequelae.