Survival after Hematopoietic Stem Cell Transplant in Patients with Dyskeratosis Congenita: Systematic Review of the Literature

Dyskeratosis congenita (DC) is a multisystem disorder, with a disruption in telomere biology leading to very short telomeres underpinning its pathophysiology. Bone marrow failure is a key feature in DC and is the leading cause of mortality. Hematopoietic stem cell transplantation (HSCT) is the only curative option for bone marrow failure in DC; however, small case reports and series have suggested a poor outcome after HSCT. We undertook a systematic review of all reported patients with DC who underwent HSCT to better characterize outcome and to identify factors associated with improved survival. The outcome of 109 patients found in the literature was poor, with 5- and 10-year survival estimates of only 57% and 23%, respectively. Patients transplanted after 2000 had improved early survival, with 5-year survival estimates of 70%; however, longer term survival was similar (28%). Pulmonary disease, infection, and graft failure were the leading causes of death. Prognosis after development of pulmonary disease post-HSCT was poor, with only 4 of 15 patients surviving at last follow-up. Multivariate analysis identified age >20 years at HSCT, HSCT before 2000, and alternate donor source to be poor prognostic markers. Reduced-intensity conditioning was not significantly found to be associated with improved survival. This review shows the poor outcome after HSCT in patients with DC and highlights the need for future collaborative clinical trials and extended follow-up of this rare patient population to define whether changes in therapy will lead to improved survival.