Evaluation of the Use of Post-Transplant Cyclophosphamide in Patients Diagnosed of Myelodysplastic Syndrome Who Undergo Allogenic Hematopoietic Cell Transplantation
Authors: Tolosa-Ridao Carles , Charry Paola , Castaño-Díez Sandra , Suarez-Lledo Maria , Merchán Muñoz Beatriz , Esteban Daniel , Cortés-Bullich Albert , Guijarro Francesca , Solano Maria Teresa , Martínez-Roca Alexandra , Jimenez-Vicente Carlos , Rosiñol Laura , Carreras Enric , Urbano-Ispizua Alvaro , Fernández-Avilés Francesc , Martinez Carmen , Esteve Jordi , Rovira Montserrat , Díaz-Beyá Marina , Salas Maria Queralt 
Published: December 2023

INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative strategy for patients with MDS. Although the outcomes of allo-HCT performed in MDS patients have improved, transplant toxicity remains a relevant limitation for determining this patient's eligibility and transplant success.
The use of PTCY for GVHD prevention is becoming a common practice in the allo-HCT community. At our institution, as in many others, PTCY-based prophylaxis has been progressively used, irrespective of the selected donor type. PTCY effectively prevents the onset of GVHD. However, its use is also associated with increased infectious complications, delayed engraftment, and specific organ toxicities.
Little is known, however, about the efficacy and safety of using PTCY in patients with MDS undergoing allo-HCT. This study reports the results of comparing the outcomes of PTCY-based versus (vs.) conventional prophylaxis in a cohort of MDS patients undergoing allo-HCT.
METHODS
This study includes the 69 patients with MDS who underwent their first allo-HCT at our institution in the years 2010 to 2022. Retrospective data were updated in June 2023. The study cohort was divided into two groups according to the GVHD prophylaxis used in the transplant platform (PTCY-based vs. other prophylaxis) in order to compare their respective outcomes.
RESULTS
The baseline characteristics of the study cohort according to the GVHD prophylaxis are shown in Table 1. Overall, the median age was 59, with 17 (24.6%) patients older than 65. According to the IPSS-R score, 11 (15.95%) patients were classified into the high-risk group, and 20 (29%) into the very-high-risk group. Fifteen (21.7%) adults underwent allo-HCT upfront, and 54 (78.3%) received prior treatment with either chemotherapy-based 7 (10.1%) or HMA-based regimens 49 (71%). Most of the baseline characteristics were balanced between the two study groups, except for the proportion of allo-HCT using 9/10 mismatched unrelated and haploidentical donors, which was higher in the PTCY group (50.0% vs. 10.3%, p&lt;0.001).
Post-transplant results are shown in Table 1. All patients engrafted. The medians of days to neutrophil (20 vs. 16, p&lt;0.01) and platelet (15 vs. 12, p&lt;0.01) engraftment were longer in patients who received PTCY. The use of PTCY resulted in similar rates of grades II-IV (Day +100 cumulative incidence (CI): 40.0% vs. 30.8%, p=0.56), in higher incidence of III-IV aGVHD (20.0% vs. 5.1%, p=0.052), and in lower rates of moderate/severe cGVHD (0% vs. 37.0%, p&lt;0.001). Post-transplant outcomes were similar in patients who received PTCY and in those who did not. The 2-years OS, RFS, NRM, CIR and GRFS of patients who received PTCY were 44.2%, 42.7%, 35.5%, 21.8% and 40.4%; for those patients that did not receive these numbers were 64.1%, 61.5%, 15.4%, 23.1% and 30.8% ( Table 1).
A multivariate analysis was performed to compare the effects of PTCY in post-transplant results (aGVHD CI, OS and NRM), controlling for covariates whose omission could bias the results of the univariate comparisons. As shown in Table 2 when controlled by donor type, patients who underwent allo-HCT with PTCY had comparable risk for presenting grades II-IV (HR 0.94, P=0.89) and III-IV aGVHD (HR 2.57, P=0.20) than patients without PTCY. The null hypothesis that patients with MDS and PTCY prophylaxis had similar transplant outcomes than those with conventional prophylaxis was not rejected: OS (HR 1.36, p=0.45), NRM (HR 2.28, p=0.21) and CIR (HR 0.39, p=0.27). The multivariate analysis also revealed that older patients (HR 1.11, p=0.01) and patients transplanted in a worse performance status (KPS&lt;90) (HR 3.40, p=0.006) had worse OS secondary to higher risk for NRM. In addition, patients classified into the very-high-risk group (HR 10.88, p&lt;0.001), and patients with a higher number of blasts prior to allo-HCT (HR 1.26, p=0.06) all had a higher risk for disease relapse.
CONCLUSION
The use of PTCY in adults undergoing allo-HCT for MDS resulted in comparable post-transplant outcomes than the use of more conventional prophylaxis but lowered the rates of moderate/severe cGHVD. Higher risk for NRM was documented in older adults and in patients with worse performance status. Furthermore, patients with a very-high-risk MDS, according to R-IPSS, were exposed to higher risk for relapse irrespective of the intensity of the conditioning regimen used as part of the transplant platform.