Second Allogeneic Hematopoietic Cell Transplant Is a Successful Salvage Modality for Pediatric Patients Who Relapse after First Transplant

Abstract

<h3>Introduction</h3> Disease relapse remains a major cause of treatment failure in pediatric patients receiving allogeneic hematopoietic cell transplantation (HCT) for high-risk acute leukemias (AL) or myelodysplastic syndrome (MDS). Comprehensive data on prognostic factors and outcomes after post-transplant relapse in pediatric patients is lacking. <h3>Objective</h3> The goal of this study was to identify factors associated with survival following post-transplant relapse. <h3>Methods</h3> We performed a retrospective study of pediatric patients who experienced disease relapse following their 1st HCT for AL or MDS between 1990 – 2018 at our institution. Patient, disease and transplant-related characteristics were extracted from the medical record. Overall survival (OS) was estimated by the Kaplan-Meier (KM) method and compared using the log-rank test. Cox and logistic regression were performed to identify factors statistically associated with outcomes after post-transplant relapse. <h3>Results</h3> During the study period, 703 patients received 1^st HCT, of which 221 (31%) relapsed at a median of 3.9 months after HCT. Of these relapsed patients, 60% (n = 132) received some chemotherapy or supportive care after post-transplant relapse, 13% (n = 28) received donor lymphocyte infusion only and 28% (n = 61) were able to proceed to a 2nd HCT. Patients who received a 2nd HCT were more likely to have been in first remission at the time of 1st HCT (<i>P</i> = 0.02), experienced relapse more than 6 months after 1st HCT (<i>P</i> < 0.001), experienced acute or chronic GVHD (<i>P</i> = 0.05 and 0.01, respectively) and relapsed in the current decade (2011 – 2018) (<i>P</i> = 0.001). Of the 61 patients who received a 2nd HCT, 18 (30%) were alive at last follow-up, compared to 7 (4%) of 160 patients who had received other therapies. In a multivariable model, longer interval from HCT to relapse (<i>P</i> < 0.001), being able to receive a 2nd HCT (<i>P</i> < 0.001) and receiving a HCT in the current decade (<i>P</i> < 0.001) were found to be significantly associated with OS (Fig 1 & 2). Factors that are typically associated with poor outcomes after HCT, such as disease status or type of HCT, donor and graft source were not predictive of survival following post-transplant relapse. <h3>Conclusion</h3> Duration of remission before post-transplant relapse was identified as the strongest independent predictor of a patient's ability to receive a 2nd HCT as well as survival after relapse. The 3-year OS for patients who received a 2nd HCT was 6 times higher than that for patients who did not receive a 2nd HCT. Although the outcomes after 2nd HCT are not commendable, they are improving with time. Our data supports the argument that, when feasible, pediatric patients experiencing post-transplant relapse should be considered for 2nd HCT.