Haploidentical Hematopoietic Cell Transplantation in Dyskeratosis Congenita with Myelodysplastic Syndrome/Acute Myeloid Leukemia.

Background: Allogeneic hematopoietic cell transplantation (Allo-HCT) is the only curative option for marrow failure, myelodysplastic syndrome (MDS), and acute myeloid leukemia associated with dyskeratosis congenita (DKC). Due to chromosomal instability and sensitivity to radiation and alkylating agents, HCT is associated with a high incidence of transplant-related mortality in DKC.

Case report: A 25-year-old male presented with DKC-associated cutaneous manifestations and myelodysplastic syndrome / acute myelogenous leukemia (MDS/AML). Targeted next-generation sequencing revealed mutation of the DKC1 and RUNX1 genes. His mother and sibling sisters were carriers for the DKC1 mutation. Due to high donor-specific antibody mean fluorescence intensity (DSA-MFI) against the unshared Human Leukocyte Antigen-A (HLA-A) allele of his 6/12 HLA-matched father, his paternal cousin's sister was selected as a haploidentical (6/12 HLA-matched) donor for HCT. He underwent allo-HCT with stable disease burden using a specifically-designed RIC regimen containing treosulfan (at 50% reduced dosing), fludarabine, and rabbit anti-thymocyte globulin. The graft versus host disease (GVHD) prophylaxis contained reduced-dose post-transplant cyclophosphamide (PTCy dose reduction of 50%) with mycophenolate mofetil and cyclosporine. He engrafted with complete donor chimerism, and the day +30 marrow was in complete morphological remission with undetectable measurable residual disease by flow cytometry. On day +126, he developed steroid-responsive late-onset grade II acute GVHD (stage III skin GVHD). He suffered from morphologic relapse on day +220 and succumbed from sepsis with septic shock on day +256.

Conclusion: This case demonstrates the safety and feasibility of haploidentical-HCT using a treosulfan-based reduced-intensity conditioning (RIC) regimen and modified PTCy-based GVHD prophylaxis in DKC. Disease relapse in this patient underscores the impact of pretransplant disease burden on relapse free survival in DKC patients with MDS/AML who are not eligible for myeloablative conditioning.