Outcomes of hematopoietic stem cell transplantation using melphalan-based conditioning in children with acquired aplastic anemia

Despite the high effectiveness of hematopoietic stem cell transplantation (HSCT) in children with acquired aplastic anemia (AAA), the procedure can still result in such major issues as graft failure and rejection. Risk factors for graft rejection and poor function as well as the persistence of mixed chimerism include allosensitization, insufficient number of transplanted cells and relatively preserved native myelopoiesis. Long-term engraftment can be achieved by modifying conditioning and immunosuppressive therapy. One such promising approach is the inclusion of melphalan in a conditioning regimen. In our study, we retrospectively analyzed outcomes of HSCT with melphalan-based conditioning carried out in 21 children with AAA (for 18 patients, it was their first HSCT, while 3 had a repeat HSCT): out of these, 11 patients received transplants from matched unrelated donors, 9 received transplants from matched related donors and 1 - from a haploidentical donor. Nine children received calcineurin inhibitor-based graft-versus-host disease prophylaxis while 12 children received Janus kinase inhibitors. A good graft function was achieved in all the children, without any severe complications. As per the latest findings, 95% of the patients achieved full total donor cell chimerism, 85.7% of the patients had full donor chimerism in the CD3+ cell lineage, while 14.3% had mixed CD3+ cell chimerism with 9-13% of own cells. The inclusion of melphalan in a conditioning regimen in patients with AAA before HSCT in combination with new less toxic graft-versus-host disease prophylaxis regimens may be an effective strategy to overcome the risk of graft rejection and ensure a low toxicity profile and low incidence of complications. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation.