Successful T-cell–depleted Haploidentical Hematopoietic Stem Cell Transplantation in a Child With Dyskeratosis Congenita After a Fludarabine-based Conditioning Regimen

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure for marrow failure associated with dyskeratosis congenita (DC). Data on transplants from alternative donors are limited. We describe a boy with DC and severe aplastic anemia who underwent haploidentical T-cell depleted HSCT using a reduced-intensity conditioning regimen. He underwent engraftment without toxicity or GVHD. His posttransplant course was complicated by EBV reactivation, treated with rituximab and EBV-specific T lymphocytes. After 26 months, he is in complete chimerism, with normal blood count and no sign of GVHD or pulmonary dysfunction. To the best of our knowledge, this is the first report of DC successfully treated with allogeneic HSCT from a haploidentical family donor.

Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation

“…A nonradiation regimen with fludarabine, lower-dose melphalan, and alemtuzumab resulted in 5 of 7 patients alive in early follow-up [76]. There has also been success in the haploidentical setting with a similar RIC approach and the use of ex vivo T cell depletion [77]. …”

Reduced intensity conditioning regimen with fludarabine, cyclophosphamide, low dose TBI and alemtuzumab leading to successful unrelated umbilical cord stem cell engraftment and survival in two children with dyskeratosis congenita

“…2 Several reports have shown that despite being a bone marrow failure syndrome, the use of reduced intensity conditioning preparative regimens are safer, carries less morbidity and has no increased risk of graft failure or rejection. 1,8,[9][10][11][12][13] In some of these reports, however, the ex vivo T-cell depletion was with ATG and in general, the source of stem cells was nonumbilical cord blood stem cells. In both patients in this report, ATG was replaced with alemtuzumab, which has more in-depth lymphocyte depletion with the hope that this will decrease any chance for rejection.…”

TCR αβ and CD19-depleted haploidentical stem cell transplant with reduced intensity conditioning for Hoyeraal–Hreidarsson syndrome with RTEL1 mutation

“…[5][6][7][8] Combination of RIC with T-cell depletion from grafts raises the concerns of non-engraftment but successful CD34 + cell selected haploidentical transplant has been recently reported. 9 Novel ex vivo T-cell depletion techniques using TCR αβ and CD19 depletion have many potential advantages. Removal of αβ-T cells by 4-5 logs can reduce the risk of GvHD but at the same time facilitates excellent CD34 + cell recovery while retaining γδ T cells, dendritic cells, natural killer (NK) cells and monocyte/myeloid cells, thereby ensuring early robust engraftment and immune reconstitution.…”