Introduction T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive precursor lymphoid neoplasm that accounts for 20% to 25% of all adult ALL cases. Allogeneic hematopoietic cell transplantation (allo-HCT) is typically recommended for adults with T-ALL in their second complete remission (CR2). However, the optimal donor type among matched sibling donors (MSD), haploidentical donors (haplo-HCT), and matched unrelated donors (MUD) remains unclear.

Methods We retrospectively analyzed data from the European Society for Blood and Marrow Transplantation (EBMT) for adult ALL patients (age ≥ 18) who underwent their first allo-HCT in CR2 between 2010 and 2022. Donors included a matched sibling (MSD), a haploidentical donor (Haplo), or an unrelated donor (UD). All enrolled patients were divided into three groups based on donor type.

Results The analysis comprised 590 patients: 106 in the Haplo group, 203 in the MSD group, and 281 in the UD group. For the entire cohort, the median age was 31 years (IQR 24, 43) and was comparable among the three groups (P = 0.23). Patients in the haplo-HCT group underwent transplantation in more recent years compared to the MSD and UD groups (median: 2019 vs. 2016 vs. 2016, P < 0.0001). Male recipients in the Haplo (28.3%) and MSD (32.3%) groups received grafts from female donors more frequently than those in the UD group (19.8%) (P = 0.006). MSD recipients (82.4%) had a higher rate of Cytomegalovirus (CMV) seropositivity compared to Haplo (58.1%) and UD (58.7%) recipients (P < 0.0001). Similarly, donors in the MSD group had a higher rate of CMV seropositivity compared to Haplo (59.6%) and UD (44.3%) donors (P < 0.0001). Baseline characteristics such as patient sex, Karnofsky performance status (KPS), and interval from diagnosis and HCT were similar among the three groups. At the time of transplant, 69.8% of the entire cohort had achieved molecular remission, which was comparable among the three groups (P = 0.61). Myeloablative conditioning (MAC) was used for 86.3% of the entire cohort. A TBI-based conditioning regimen was performed less frequently in the Haplo group (46.2%) than in the MSD (60.4%) and UD (71.5%) groups (P < 0.0001). In the Haplo group, 68.3% of patients received post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis.

In univariate analysis, no significant differences were observed among the three groups for 2-year overall survival (OS) (Haplo 46.4% vs. MSD 42.5% vs. UD 43.3%, P = 0.88), 2-year progression-free survival (PFS) (Haplo 35.9% vs. MSD 37.1% vs. UD 35.6%, P = 0.98), 2-year relapse incidence (RI) (Haplo 39.7% vs. MSD 46.3% vs. UD 42.7%, P = 0.32), and 2-year non-relapse mortality (NRM) (Haplo 24.4% vs. MSD 16.6% vs. UD 21.7%, P = 0.17). The 180-day cumulative incidence of grade II–IV acute GVHD was comparable among Haplo (32.5%), MSD (29.0%), and UD (34.3%) recipients (P = 0.52). The incidence of grade III–IV acute GVHD was also comparable among Haplo (15.7%), MSD (10.7%), and UD (12.7%) recipients (P = 0.46). Additionally, the 2-year cumulative incidence of overall chronic GVHD was comparable in Haplo (20.3%), MSD (26.8%), and UD (26.1%) recipients (P = 0.6).

In multivariate analysis, no significant difference was found among the three donor types for OS, PFS, RI, and NRM. Notably, a TBI-based regimen was associated with superior OS (HR = 0.71, P = 0.03) and PFS (HR = 0.7, P = 0.02), and improved NRM (HR = 0.56, P = 0.03), compared to a BuCy/BuFlu-based regimen. Concerning GVHD, there were no significant differences among the three donor types in the incidence of grade II–IV acute GVHD, grade III–IV acute GVHD, or overall and extensive chronic GVHD. Cytomegalovirus (CMV) seropositivity in recipients was associated with a higher risk of overall chronic GVHD (HR = 1.64, P = 0.04). A TBI-based regimen was associated with a lower risk of grade II–IV acute GVHD (HR = 0.65, P = 0.04) and grade III–IV acute GVHD (HR = 0.53, P = 0.04) compared to a BuCy/BuFlu-based regimen.

Conclusions For T-ALL patients in CR2, HCT from MSD, Haplo, and UD resulted in comparable outcomes, including OS, PFS, RI, NRM, aGVHD, and cGVHD. Both haploidentical and unrelated donors can be selected as viable alternative donors.

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2025
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