Severe Aplastic Anemia (SAA) is the most frequent indication for Hematopoietic Cell Transplantation (HCT) for nonmalignant diseases in Brazil. Survival after HCT from HLA-Matched Related (MRD), HLA-Matched Unrelated (MUD), and Haploidentical Donors (HID) has improved over the past decades. We aimed to compare the outcomes of a large cohort of patients (pts) submitted to HCT for acquired SAA in Brazil.

A retrospective, non-randomized study included 328 pts with acquired SAA who underwent HCT in 5 Brazilian HCT centers between 01/2012 and 12/2022. All pts received bone marrow as the graft source from MRD (n = 154), MUD (n = 96), or HID (n = 78). MUD was defined as HLA 10/10 or 8/8.

Pts and donors’ characteristics are summarized in Table 1. Median follow-up after HCT was 4.7 years. Median age was 18.4 years (1‒69 years), most were CMV positive and heavily transfused. 74% had received previous immunosuppression with (n = 09) or without Rabbit-ATG (n = 134). Median disease duration before transplant was 7 months (0.6‒184), however pts with a MRD were transplanted earlier. There were some statistical differences among groups: HID were performed more recently and ATG was more frequently used in MUD. Conditioning regimen and GVHD prophylaxis were also different among donor groups. One-year cumulative incidence of Graft Failure (GF) in MRD, MUD, and HID cohort was 4.8%, 10.8% and 18.1% (p = 0.0028), respectively. 27 pts were rescued with a 2nd transplant (MRD, n = 7;MUD, n = 8;HID, n = 12) at a median of 40 days after 1st HCT, and 14 are alive. In a Multivariate Analysis (MVA), MUD-HCT (HR = 2.35, p = 0.078) and HID-HCT (HR = 4.30, p = 0.0012) were associated with a higher incidence of GF (Table 2). MRD-HCT had a lower incidence of grade II–IV acute graft versus host disease (aGvHD) compared with MUD and HID (12.4% vs. 30.3% vs. 16.9%, p = 0.00175) and lower incidence of chronic GvHD (cGvHD) (8,7% vs. 26,9% vs. 27.2%, p ≤ 0.001).The estimated non adjusted 5-year Overall Survival (OS) for the MRD, MUD, and HID groups were 86%, 72% and 79% (p = 0.02), respectively; event-free survival (event: rejection or death) rates were 85%, 68% and 56%, respectively (p < 0.001) (Figs. 1 and 2). In MVA, OS was increased for transplantations after 2018 (HR = 0.38, p = 0.002) (Fig. 3). MUD-HCT (HR = 3.13, p≤0.001) and HID-HCT (HR = 2.97, p = 0.0039) were associated with decreased OS in comparison to MRD-HCT. The 100-day CI of CMV reactivation and hemorrhagic cystitis were 56% and 8% respectively, with no significant differences between groups. 64 pts died at a median of 102 days (range 2–2328), and the main causes of death were GF, n = 20; sepsis, n = 11; GvHD, n = 9.

This retrospective analysis showcases some significant differences between donor groups, including the fact that MRD pts are transplanted earlier and are subjected to a lower risk of GF, acute and chronic GVHD, which translates into better survival. HID-HCT showed improved survival in recent years, becoming a more viable transplant option, specially in comparison to MUD-HCT. Improved OS in HID-HCT comes at the expense of higher rates of graft rejection and higher rates of aGvHD remain an issue after MUD-HCT.

These real-world data from a large cohort of SAA pts demonstrate that HCT remains an effective curative treatment with significant improvement in survival in the last 5 years across different donor groups.