Improved Outcomes with Myeloablative Conditioning in AML Patients below 65 Years Using a Combination of Antithymocyte Globulin and Post-Transplantation Cyclophosphamide As Gvhd Prophylaxis
Authors: Alnughmush Ahmed , Alyamany Ruah , Remberger Mats , Pasic Ivan , Novitzky-Basso Igor , Law Arjun , Lam Wilson , Kim Dennis Dong Hwan , Michelis Fotios , Gerbitz Armin , Kumar Rajat , Mattsson Jonas , Viswabandya Auro 
Published: December 2024

Background:

Allogeneic hematopoietic cell transplantation (Allo-HCT) is a critical treatment option for achieving long-term remission in patients with acute myeloid leukemia (AML), particularly those with intermediate or high-risk disease. Although myeloablative conditioning (MAC) improves disease control and reduces relapse rates, resulting in a survival advantage, it is also associated with increased non-relapse mortality. This study compares the outcomes of myeloablative (MAC) versus reduced-intensity conditioning (RIC) in AML patients undergoing Allo-HCT, all of whom received a unified GVHD prophylaxis regimen of a combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy).

Methods:

We conducted a retrospective analysis of 322 AML patients who underwent Allo-HCT at Princess Margaret Cancer Centre between October 2015 and October 2023. Patients were under the age of 65 and received a standardized GVHD prophylaxis regimen that included ATG, PTCy, and cyclosporine. The primary outcomes assessed were overall survival (OS), relapse-free survival (RFS), GVHD-free/RFS (GRFS), acute and chronic GVHD, and graft failure.

Results:

Of the 322 patients, 207 received RIC (Fludarabine 35 mg/m²/day for 4 days + Busulfan 3.2 mg/kg/day for 2 days + TBI 200), while 115 received MAC (Fludarabine 35 mg/m²/day for 4 days + Busulfan 3.2 mg/kg/day for 4 days). The median age was significantly lower in the MAC group compared to the RIC group (46 years vs. 57 years, p&lt;0.001). Matched unrelated donors (MUD) were the predominant donor type (53.7%), followed by haplo-donors (20.2%), mismatched unrelated donors (MMUD) (13.4%), and matched related donors (MRD) (12.7%). A greater proportion of patients in the RIC group had a hematopoietic cell transplant comorbidity index (HCT-CI) ≥3 (44.1% vs. 18.3%, p&lt;0.001).

There was a trend favoring MAC for 2-year OS (72.5% vs. 63.8%, p=0.09) over RIC. The 1-year NRM did not differ significantly between the RIC and MAC groups (14.3% vs. 13.5%, p=0.96). The 2-year relapse rate was significantly higher in the RIC group compared to the MAC group (29% vs. 18%, p=0.04).

The incidence of acute GVHD grade I-IV by day 100 was higher in the MAC group than in the RIC group (43.5% vs. 30%, p=0.01). However, there were no significant differences between the groups for acute GVHD grade II-IV (22.6% vs. 15.9%, p=0.23) or grade III-IV (5.2% vs. 5.3%, p=0.84). The 2-year incidence of chronic GVHD was similar between the groups (MAC 16.3% vs. RIC 22.6%, p=0.30). Consequently, the 2-year GRFS was comparable between MAC and RIC (54.8% vs. 49%, p=0.31). Regarding graft failure, there was no significant difference between the groups (MAC 2.6% vs. RIC 1.9%, p=0.68). The incidence of bloodstream (BSI) post-HCT was also similar (MAC 55.7% vs. RIC 44%, p=0.18). Notably, the RIC group had a significantly higher risk of CMV reactivation compared to the MAC group (50.4% vs. 34.8%, p=0.009).

Conclusion:

Our data suggest that though MAC was associated with less relapse rate, it was not found to be associated with superior overall survival or GRFS while using a combination of ATG and PTCy, that effectively manages the risk of higher-grade acute and chronic GVHD.