Despite the progress in Haploidentical Stem Cell Transplantation (HSCT), many patients do not have a suitable healthy family donor. Transplants from matched unrelated donors would be ideal, but they are not available to most patients. One emerging treatment option is to use mismatched unrelated donors with PT-Cy to avoid GVHD, especially in patients with non-malignant diseases. Diamond Blackfan Anemia (DBA) is caused by a defect in erythropoietic progenitors, resulting in severe anemia of very early onset, usually before the first year of life. First-line treatment options for DBA are regular red blood cell transfusions, iron chelation, and corticosteroids, but only 40% of the patients respond to the latter. Thus, allogeneic HSCT is the only curative treatment for the hematological manifestations of this disease. The main difficulty is to identify a healthy HLA-identical donor, what limits the access of many patients to this curative therapy.

To describe the strategy using an unrelated donor with Class I antigenic HLA incompatibility and PT-Cy to prevent GVHD.

The best available donors are chosen in a regular meeting with the Institute of Immunogenetics (IGEN) team, in which all haploidentical family members are considered, with corresponding ABO typing, age and weight, as well as the national and international donor searches. The anti-HLA panel is always considered. Conditioning regimens are chosen based on the Pediatric BMT Group of the SBTMO consensuses. GVHD prophylaxis with PT-Cy, mycophenolate mofetil and cyclosporine are used in haploidentical transplants and, more recently, also for mismatched unrelated donors. The preferred graft source is always the bone marrow, except in extreme conditions with an expected increased chance of graft failure.

A 1 year and 6 months baby girl was diagnosed with DBA at the age of 2-months of life. She remained transfusion-dependent after two steroid cycles. No HLA-compatible related or unrelated donor was found. A 38-year-old unrelated male donor was chosen, with compatible ABO typing and two HLA mismatches, antigenic incompatibility in the A locus and a permissive DP mismatched (HLA 10×12). Conditioning was based on the SBTMO 2021 consensus, with Busulfan, Fludarabine and ATG. Due to the A mismatch, GVHD prophylaxis included PT-Cy, MMF and CsA. After a fresh bone marrow graft, she had neutrophilic engraftment on D+18 and platelet engraftment on D+28. She had no important side effects and was discharged from the hospital on D+21. On D+29 she was admitted with bloody diarrhea due to adenovirus and developed upper respiratory infection due to Parainfluenza. The child currently remains on cyclosporine, with no signs or symptoms of GVHD, with complete chimerism and good graft function.

The use of PT-Cy may overcome class I mismatches in the unrelated donor setting and expand the donor pool and the results of these transplants.