In patients with advanced chronic myeloid leukemia (CML), allogeneic hematopoietic cell transplantation (allo-HCT) has been shown to provide a T-cell-driven graft-versus-leukemia (GvL) effect, which is crucial for controlling disease relapse after transplantation, despite associated nonrelapse mortality (NRM) rates.
A critical aspect of allo-HCT success is the type of donor selected. Allo-HCT from matched sibling donors (MSDs) is associated with lower NRM and higher overall survival (OS) compared with matched unrelated donors (MUDs) and mismatched unrelated donors (MMUDs). However, the limited availability of MSDs means that a search for compatible unrelated donors (UDs) is often necessary. Allo-HCT from UDs comes with higher risks, primarily due to human leukocyte antigen (HLA) mismatches, leading to a higher rate of both graft versus host disease (GvHD) and NRM. Various strategies have been adopted to reduce GvHD rates, including T-cell depletion and using bone marrow as the graft source. Despite these efforts, allo-HCT from UDs typically yields worse outcomes compared with MSDs.
Assessing Post-Transplant Cyclophosphamide
In recent years, post-transplant cyclophosphamide (PTCy) has emerged as a successful method for GvHD prophylaxis, enabling the use of mismatched related donors (MMRDs), especially haploidentical donors (HDs), in allo-HCT. The use of PTCy was pioneered in a nonmyeloablative HD transplant platform, providing satisfactory results. Subsequently, using PTCy as GvHD prophylaxis has expanded across a range of indications and donor types. Retrospective studies suggest that outcomes after allo-HCT from MMRDs using PTCy are comparable to those using UDs or MSDs in various hematological malignancies.
However, “outcomes following allogeneic hematopoietic cell transplantation for chronic myeloid leukemia with post-transplant cyclophosphamide utilizing an unrelated donor or mismatched related donor remain unknown,” wrote Guillermo Ortí, MD, and colleagues in Transplantation and Cellular Therapy. To evaluate the use of PTCy in allo- HCT from UDs and MMRDs in patients with CML, the authors conducted a retrospective, multicenter, registry-based analysis, approved by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Data were collected from patients with CML who underwent their first allo- HCT between 2012 and 2019. The study compared outcomes in three donor/GvHD prophylaxis cohorts: PTCy UDs, non-PTCy UDs, and PTCy MMRDs. Patients aged 18 and older and in various disease phases were included, whereas those with matched sibling donors and cord blood grafts were excluded. The primary endpoint of the study was GvHD relapse-free survival (GRFS), with secondary endpoints including overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (RI), NRM, cumulative incidence of grade 2-4 acute GvHD, and cumulative incidence of chronic GvHD.
Additional Options for Allo-HCT in CML
During a median follow-up of 34.9 months, 3-year GRFS rates were 43% in the non- PTCy UD cohort, 37%, in the PTCy-UD cohort, and 39% in the PTCy MMRD cohort. Among 1,341 patients with CML from 257 EBMT centers, no significant differences in GRFS, OS, PFS, NRM, and GvHD rates were observed across the three donor/GvHD prophylaxis groups. “Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Score less than 90 (HR, 1.86; 95% CI, 1.41-2.45; P<0.001), older age (HR, 1.24; 95% CI, 1.11-1.38; P<0.001) and disease stage,” the researchers reported. Regarding disease stage, results were as follows when compared with the first chronic phase (CP1): blast phase (HR, 2.25; 95% CI, 1.60-3.16; P<0.001), accelerated phase (HR, 1.63; 95% CI, 1.05-2.54; P=0.03), and second or higher chronic phase (HR, 1.58; 95% CI, 1.15-2.17; P=0.005). “These results suggest that allo-HCT in CML utilizing either an UD or MMRD with a PTCy GvHD-based prophylaxis are feasible transplant platforms and that the disease stage at allo-HCT remains a major prognostic factor,” wrote Dr. Ortí and colleagues, “highlighting the importance to closely monitor [patients with CML] and propose transplantation when indicated, when still in CP1.” The authors emphasize the importance of close monitoring and timely intervention for patients with chronic myeloid leukemia when considering allo-HCT.
