Transplant outcomes for children and adolescents with severe aplastic anemia comparing matched sibling donor and haploidentical transplant approaches.

Abstract Introduction Recent studies comparing matched sibling donor (MSD) and haploidentical donor with post-transplant cyclophosphamide (haplo-PTCy) hematopoietic stem cell transplantation (HSCT) for children and adolescents with severe aplastic anemia (SAA) show promising results. While MSD-HSCT remains the preferred option with better survival outcomes and lower incidence of acute graft-versus-host disease (GVHD), haplo-PTCy has emerged as a viable alternative when an MSD is unavailable. Both approaches significantly improve quality of life post-transplant. [1 2 3] Methods A retrospective review was made of 20 patients with a history of SAA who received transplants between January 2014 and December 2024 at the National Institute of Pediatrics in Mexico City. Results Twenty patients diagnosed with SAA underwent HSCT. The cohort included thirteen males and seven females, with a median age at transplant of 10 years (range: 2–17 years). Thirteen patients received a transplant from an MSD; in ten of these cases, bone marrow was used as the source of hematopoietic stem cells (HSC). The conditioning regimen consisted of cyclophosphamide (Cy) 200 mg/kg and antithymocyte globulin (Thymoglobulin, ATG) at a total dose of 10 mg/kg. GVHD prophylaxis included cyclosporine A (3–5 mg/kg) and mini-methotrexate. Among the seven patients who underwent Haplo-PTCy, five received bone marrow as the graft source. The conditioning regimen included ATG 4.5 mg/kg, fludarabine 150 mg/m², and total body irradiation 400 cGy. GVHD prophylaxis consisted of Cy 50 mg/kg on +3 and +4, followed by tacrolimus 0.06 mg/kg and mycophenolate mofetil 30 mg/kg starting on +5. Overall survival was 85%, with rates of 84.6% in the MSD group and 85.7% in the Haplo-PTCy group (p = 0.950). There were no statistically significant differences in the time to engraft between both transplant models. Median time to neutrophil engraftment was 19 days in the MSD group (range, 11–38) vs 17 days in the Haplo-PTCy group (range, 11–38; p = 0.472). Red blood cell engraftment occurred at a median of 30 days in the MSD group (range, 6–55) and 32 days in the Haplo-PTCy group (range, 6–103; p = 0.763). Platelet engraftment was achieved at a median of 36 days in the MSD group (range, 8–142) vs 24 days in the Haplo-PTCy group (range, 10–35; p = 0.397). One patient in each group presented primary graft failure. In the MSD group, the patient died due to complications from pulmonary aspergillosis. In the Haplo-PTCy group, one patient died because of complications related to cytomegalovirus infection in the setting of grade IV gastrointestinal aGVHD. A higher incidence of grade III–IV acute graft-versus-host disease (aGVHD) was observed in the Haplo-PTCy model, with 4 out of 7 patients (57.1%) affected, compared to the MSD group (OR = 2.3; p = 0.003; 95% CI: 0.992–5.4), however, these results should be interpreted with caution due to the small size of the cohort studied. Discussion and Conclusions Health-related quality of life outcomes is comparable between the two approaches, with no significative differences in overall survival between both transplant models. These results suggest that haplo-HSCT with PT-Cy is a viable alternative when an MSD is unavailable and may open the possibility of further research studies in which this transplant model is considered as a first line of treatment in children and adolescents with SAA. References Valencia DM, Builes N, Franco AA, et al. Outcomes of Matched Sibling and Haploidentical Donors Hematopoietic Stem Cell Transplantation for Pediatric Severe Aplastic Anemia: A Retrospective Multicenter Study. Hematol Oncol Stem Cell Ther. 2025;18(2):72-78. Kim H, Im HJ, Koh KN, et al. Comparable Outcome with a Faster Engraftment of Optimized Haploidentical Hematopoietic Stem Cell Transplantation Compared with Transplantations from Other Donor Types in Pediatric Acquired Aplastic Anemia. Biol Blood Marrow Transplant. 2019;25(5):965-974. Im HJ, Koh KN, Seo JJ. Haploidentical hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia. Korean J Pediatr. 2015;58(6):199-205.