Post-Transplant Cyclophosphamide Is Feasible and Reduces Acute GvHD in Pediatric UCB Transplantation

Post-transplant Cyclophosphamide (Post-Cy) has demonstrated to decrease the occurrence of aGVHD in preclinical and haploidentical studies. Nevertheless, Post-Cy increases time to neutrophil recovery, an issue that is of utmost importance for UCB transplant related mortality (TRM). We postulated that despite UCB lower cellular doses, the use of Post-Cy decreases graft vs host and host vs graft reactions, enhancing engraftment, and improving clinical outcomes. So we explore the feasibility of using Post-Cy in the setting of UCB transplantation in children. In June/2010, our group decided to include post-Cy for UCB transplantation. A single 50 mg/kg/dose of Cy was added on day +3. CSA and MMF was started day +4, as well as G-CSF. Post-Cy was used both in RIC and myeloablative transplants. Rabbit ATG or Alemtuzumab was used only for RIC transplants. The group that received Cy-Post (21 cases) was compared with our previous UCB transplantation cases (35 cases) where Post-Cy was not used. Multivariate logistic regression models were used to evaluate the independence of the relationship between Cy-Post and aGvHD, of other covariates such as, age, gender, RIC, HLA match, CMV receptor status, pre-freezing TNC and CD34. Attached table compares characteristics of patients with and without Post-Cy. No significant differences were identified among the 2 groups. The groups with and without Post-Cy were infused  with 7.1 vs 6.4x10⁷ TNC/kg, and 2.84 vs 2.81x10⁵ CD34+cells/kg, respectively. 100-day (25% vs 26%) and 1-year (25% vs 31%) TRM and overall survival (60% vs 57%) were not different among the groups. Median time to neutrophil and platelet engraftment with and without Post-Cy was 24 vs 16 days (P<0.01), and 43 vs 35 days (P=0.02), respectively. Forty-nine (87.5%) patients were evaluable for aGvHD, 49% were classified as grades II-IV. In the group with Post-Cy grades II-IV aGvHD was 32% compared with 68% in the group without Post-Cy. OR was 0.31 (95%CI:0.1, 1.0), and adjusted OR was 0.16 (95%CI: 0.03, 0.78), P=0.02. No documented cases of grade IV aGvHD in the Post-Cy group. In conclusion, we found an important effect of Post-Cy over the occurrence of aGVHD, independently of HLA match, and of other relevant variables. Neither, we find an effect over early TRM, and is uncertain its impact over long term mortality. We hypothesize that usage of Post-Cy in UCB transplantation in children, can allow the use of UCB units with greater HLA mismatch, and thus, increasing the potential pool of grafts available for transplantation. This could be especially useful for ethnic minorities.