Hematopoietic Stem Cell Transplant in Adult Patients with Fanconi Anemia: A Review

TL;DR

This paper reviews the challenges and considerations of hematopoietic stem cell transplants in adult Fanconi Anemia patients, highlighting unique clinical and treatment issues.

Contribution

The paper provides a case-based review and incorporates recent findings to guide the care of adult Fanconi Anemia patients undergoing transplants.

Findings

Fanconi Anemia is increasingly diagnosed in adults due to advanced genetic testing.

Standard conditioning regimens are unsuitable for FA patients due to heightened sensitivity to alkylating agents and radiation.

FA patients have a higher risk of developing squamous cell cancers post-transplant.

Abstract

Fanconi anemia (FA) is characterized by faulty DNA repair and is associated with bone marrow failure, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). Because of the more widespread use of next-generation sequencing (NGS) and increased testing for germline mutations in young patients with MDS and AML, FA is increasingly being first diagnosed in adults, many of whom lack classical physical stigmata. Hematopoietic stem cell transplant is the only cure for the hematologic manifestations of FA but there are several unique considerations in FA patients, including first maintaining a high index of suspicion for the diagnosis in patients with minimal phenotypic abnormalities, second an exaggerated sensitivity to alkylating agents and radiation, precluding the use of standard myeloablative conditioning regimens despite the young age of most of the patients, and lastly a marked propensity for squamous cell cancers of the upper aerodigestive tract and anogenital region, likely further increased by the drugs used in conditioning and by chronic inflammation in patients who develop graft-versus-host disease. Despite a growing number of FA patients surviving into adulthood or first being diagnosed with FA as an adult, there is minimal literature describing transplant methodology and outcomes. In the following case-based review of a patient, we incorporate recent findings from the literature on the care of this challenging patient population.

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