Late Effects After Hematopoietic Stem Cell Transplantation Among Childhood Transplant Survivors with Fanconi Anemia.

Background: Fanconi anemia is the most common inherited bone marrow failure syndrome. HSCT remains the only curative treatment for hematological manifestations of FA. Despite restoration of long-term hematopoiesis, patients continue to remain at risk of late effects.

Objectives: In our study, we aimed to reveal the problems that occur in the long-term follow-up of FA patients, and point out an ongoing need for the improvement of long-term follow-up guidelines for childhood transplant survivors with FA.

Study design: In this single centered, cross-sectional study, we analyzed the long-term outcome of 36 patients with FA according to current recommendations with a median age of 18.1 years (range: 6.1-36 years, male/female, 24/12) who underwent a HSCT at Pediatric Bone Marrow Transplantation (BMT) Unit between 1995 and 2019 and survived at least one year post-transplant.

Results: The median long-term follow-up time was 8 years (range, 1-25 years). Gonadal dysfunction was detected in about 35% of our patients. 31% of the patients had hypergonadotropic hypogonadism, 4 % had hypogonadotropic hypogonadism. When the patients were evaluated for growth impairment, 7 of 12 patients who reached their final adult height and 12 of 21 patients who didn't complete their growth, had height standard deviation score below -2 SD. Three patients (9%) developed subclinical hypothyroidism, two (6%) had overt hypothyroidism and one (3%) had central hypothyroidism. Although, none of our patients fully met the criteria for metabolic syndrome, 23% of the patients had insulin resistance and 39% had dyslipidemia. Evaluation of organ dysfunctions revealed that almost 50% of the patients had obstructive and 21 % had restrictive changes in their pulmonary function tests. Hepatosteatosis was detected in 15% of the patients and mild valve dysfunction was detected in 50 % of evaluable patients. Three patients developed secondary malignancies. Squamous cell cancer developed in 2 patients and basal cell cancer in one patient.

Conclusion: A risk-defined multidisciplinary approach for long-term follow up of children with FA undergoing HSCT is essential for early detection and management of late effects.