Better Transplant Outcomes with Umbilical Cord Stem Cells in Patients with Dyskeratosis Congenita

Background:Dyskeratosis congenita (DKC) is a rare genetic bone marrow failure (BMF) syndrome of unknown etiology with a multisystem involvement and predisposition for cancer. It presents as a classic triad of dystrophic nails, oral leukoplakia and skin hyperpigmentation. Hematopoietic stem cell transplant (HSCT) has been tried as a treatment option but there is limited data on outcomes in these patients.

Methods:As the disease is rare with high mortality, there have been no prospective studies. Retrospective database analysis is an effective means to evaluate outcomes in this patient population. Our study utilized Pediatric Health Information Systems (PHIS) database, which is an administrative quality-controlled database from 43 not-for-profit children's hospital, to analyze healthcare outcomes in pediatric patients with DKC. ICD-9 code 757.39 was used to identify the disease classification and as the only condition with an indication for stem cell transplant, we isolated the cases that underwent HSCT with that diagnostic code.

Results: A total of 40 patients with DKC were identified who underwent transplant. A higher incidence was noted in Caucasian males with no significant difference in mortality across gender and ethnicity. The median length of hospitalization was 48 days (range 8.5 to 160.5 days) with a mean age of hospital admission at 93 months (95% CI: 70, 117). All the transplants were allogeneic with almost 20% umbilical cord (UCT) stem cell transplants. There was 15% mortality noted in this patient population, with all of deaths occurring prior to 2012. The complication rate (including acute and chronic GVHD as well as graft failure) was noted to be 37.5%, with acute GVHD being most common (20%). Fludarabine, Alemtuzumab, Cyclophosphamide, and Melphalan based conditioning regimen were most commonly used. Cyclosporine (65%), steroids (80%), Mycophenolate mofetil (50%) and Tacrolimus (40%) were commonly used for GVHD prophylaxis. Despite small numbers, significantly lower mortality was noted in UCT as compared to the other allogeneic stem cell transplants (p<0.01).

Conclusion: Limited literature is available on pediatric transplant outcome data in DKC. UCT has better transplant outcomes in DKC patients due to longer telomere lengths of donor stem cells. Larger studies are needed for to compare transplant outcomes from different sources.