title: A Reduced-Intensity Conditioning Regimen for Patients with Dyskeratosis Congenita Undergoing Hematopoietic Stem Cell Transplantation.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for progressive marrow failure, myelodysplastic syndrome, or leukemia associated with dyskeratosis congenita (DC). HSCT for DC is limited by a high incidence of treatment-related mortality, thought to be related to underlying chromosomal instability and sensitivity to chemotherapy and radiation. We report our experience in 7 patients with DC who underwent allogeneic transplantation using a reduced-intensity conditioning (RIC) preparative regimen that contained chemotherapy only (no radiation). This RIC regimen, designed specifically for patients with DC, contained alemtuzumab, fludarabine, and melphalan (with melphalan at 50% reduced dosing), with the goal of decreasing toxicity and improving outcome. All 7 patients engrafted, with none developing mixed chimerism or rejection. Two patients experienced acute graft-versus-host disease (GVHD) and 1 went on to develop limited chronic GVHD of the skin. Five patients remain alive and well at a median follow-up of 44 months (range, 14 to 57 months). We conclude that a radiation-free RIC regimen results in durable engraftment, acceptable toxicity, and improved overall survival in patients with DC undergoing allogeneic HSCT.
authors: Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Adam.nelson@cchmc.org.
authors: Adam S
authors: AS
authors: Nelson
authors: Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Rebecca A
authors: RA
authors: Marsh
authors: Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Kasiani C
authors: KC
authors: Myers
authors: Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Stella M
authors: SM
authors: Davies
authors: Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Sonata
authors: S
authors: Jodele
authors: Kids Cancer Centre, Sydney Children's Hospital, Randwick NSW Australia.
authors: Tracey A
authors: TA
authors: O'Brien
authors: Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Parinda A
authors: PA
authors: Mehta
mesh_terms: D000293:Adolescent; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018572:Disease-Free Survival; D019871:Dyskeratosis Congenita / Q000401:mortality* / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012871:Skin Diseases / Q000401:mortality; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*
keywords: Dyskeratosis congenita; Hematopoietic stem cell transplantation; Reduced-intensity conditioning