Effects of Post-Transplant Cyclophosphamide on Outcomes of Allogeneic Stem Cell Transplant Are Different between Older and Younger Adult Patients: A Single Institutional Experience
Authors: Stapor Daniel , Shestovska Yuliya , Styler Michael , Abdelmessieh Peter , Khanal Rashmi , Fung Henry C. , Ojala Anne , Varshavsky Yanovsky Asya 
Published: December 2024

Introduction
Allogenic hematopoietic stem cell transplantation (allo-HSCT) offers a potential curative option for multiple malignant hematologic diseases and some non-malignant conditions. Pediatric patients have the best outcomes following allo-HSCT while the adolescent and young adult (AYA) population, aged 18-39 years old (yo), has a significantly inferior prognosis for post-transplant outcomes. These worse outcomes include increased non relapse mortality (NRM), lower overall survival (OS), increased infectious complications, and increased rates of acute and chronic graph vs host disease (aGVHD/cGVHD). Unlike the documented disparity in outcomes between AYA and pediatric patients after allo-HSCT, the difference between AYA outcomes and all other adults is less known. Given the limited data comparing AYA patients to older adults undergoing allo-HSCT, we aimed to further investigate the differences between these two patient populations. We also analyzed the outcomes post-transplant Cyclophosphamide (PTCy) vs non-PTCy GVHD prophylaxis (ppx) in different age groups.
Methods
This was a single-center, retrospective chart review study from the Fox Chase-Temple University Hospital Bone Marrow Transplant Program. Chi square and Anova test were used for statistical analysis.
Results
429 patients received an allo-HSCT at our center between 2007-2021, with 81 being AYA, 256 being 40-60 yo, and 92 being 61+ yo. At baseline, sex, donor type, and stem cell source distribution were similar across all groups; diagnoses were relatively uniform, with age-appropriate variations. AYA patients had a higher proportion of myeloablative regimens (AYA 71% vs 40-60 yo 57% vs 61+yo 33%) and lower porportion of PTCy GVHD ppx (47% vs 51% vs 69%) compared to the other age groups.
The overall differences in 1 and 3 year OS following allo-HSCT among the three age groups were not statistically significant with a slight trend towards better OS in the AYA population. Comparing the outcomes for patients who received PTCy vs non-PTCy GVHD ppx, 1 year NRM was significantly better with PTCy in older patients (40-60 yo 4.9% vs 19.8%, p .0004; 61+yo 6.6% vs 22.2%, p .032), but similar for AYA patients with or without PTCy (14.3% vs 15.3%, p .894). 1 and 3 year OS were similar between PTCy and non-PTCy GVHD ppx in the AYA group (1y: 71.4% vs 69.2%: p .836; 3y 56.7% vs 48.7%, p .713), but significantly better with PTCy for 40-60 yo (1y 75.4% vs 48.6%, p .0058; 3y 58.4% vs 41.4%, p .0099), and numerically better for 61+yo (1y 75.4% vs 55.6%, p .0625; 3y 50% vs 40.7%, p .428).
We also analyzed the incidence of aGVHD and cGVHD across age groups and GVHD ppx groups, including only patients with PBSC graft source. Across the age groups, there was no difference for those who received PTCy vs non-PTCy GVHD ppx in rates of grade 3-4 (G3-4) aGVHD (AYA 5.9%, 40-60 yo 7.7%, 61+yo 11.7%, p .557) or moderate/severe cGVHD (16% vs 9.2% vs 11%, p .613). Within each age group, those that received PTCy had reduced rates of GVHD compared to those that did not receive PTCy. There was a numerical trend towards favorable outcomes for G3-4 aGVHD for AYA patients with PTCy vs non-PTCy GVHD ppx (5.9% vs 16.7%, p .184), and similar moderate/severe cGVHD (16% vs 23.1%, p .59). However, in patients 40+yo, there was significant improvement in GVHD outcomes with PTCy vs non-PTCy GVHD ppx (G3-4 aGVHD 9% vs 34.1%, p &lt;.000001; moderate/severe cGVHD 9.8% vs 30.6%, p .0016). Lastly, rates of secondary myeloid malignancies were numerically less in AYA patients than patients 40+yo (1.5% vs 4.3%, p .298), though rates were similar between AYA and 40+yo for non-myeloid malignancies (4.6% vs 4.3%, p .878).
Conclusions
Our results indicate that the use of PTCy GVHD ppx was associated with decreased rates of aGVHD compared to non-PTCy GVHD ppx, most prominently in patients 40+yo, with associated improvement in NRM and OS outcomes in this population. In the AYA population, there was a lesser effect of PTCy on aGVHD incidence and survival outcomes overall. Among all patients treated with PTCy, the outcomes of the AYA population appear to align with all adults 40+yo. Notably, the rates of post-transplant non-myeloid malignancies were higher than expected and similar to older patients in the AYA population, indicating the importance of screening AYA allo-HSCT patients based on survivorship guidelines rather than only following age appropriate cancer screening recommendations.