PharmD Candidate University of North Carolina Eshelman School of Pharmacy Chapel Hill, North Carolina, United States
Poster Abstract:
Background: Allogenic hematopoietic stem cell transplant (allo-HCT) is a potentially curative treatment for hematologic malignancies and nonmalignant bone marrow disorders. Myeloablative conditioning (MAC) chemotherapy regimens, which include busulfan/cyclophosphamide (BuCy) and fludarabine/busulfan (FluBu), are considered standard-of-care for hematologic malignancy diagnoses prior to allo-HCT. BuCy and FluBu regimens are considered the most effective therapies, but patients still experience disease relapse or chemotherapy-induced toxicities. Even with pharmacokinetically (PK)-guided busulfan dosing strategies, patients may experience grade 1-4 liver function test (LFT) elevations, as defined by Common Terminology Criteria for Adverse Events (CTCAE), disease relapse, or hepatic sinusoidal obstruction syndrome (SOS) following MAC conditioning. Therefore, there remains a critical need to better understand the relationships between MAC conditioning regimens, busulfan PK, and clinical outcomes. Recently, transplant centers have begun to routinely collect donor chimerism following allo-HCT, with the goal of achieving full donor cells in the bone marrow (i.e., full donor chimerism) before Day 100 post-transplant (Day +100). Utilizing donor chimerism as a marker of allo-HCT success is a relatively new approach that may help better identify factors associated with successful allo-HCT.
Objective: To determine the impact of MAC conditioning regimens and busulfan AUCs on donor chimerism (Day +30, +60 and +90), incidence of SOS, and clinical outcomes (RFS and OS).
Methods: This single-center, retrospective cohort study identified patients who received an allo-HCT at UNC Medical Center between 4/4/2012 and 2/17/2023. Patients undergoing their first allo-HCT who received MAC with BuCy or FluBu were eligible for inclusion. Patients were excluded if they were less than 18 years-old, received reduced-intensity conditioning (RIC) chemotherapy, received any other MAC regimen (e.g., CyTBI), or had received a previous allo-HCT. The primary outcome was the difference in Day +30 chimerism rates between allo-HCT patients who received MAC FluBu versus MAC BuCy. Secondary outcomes included differences in Day +60 and +90 chimerism rates between MAC FluBu versus MAC BuCy, associations between busulfan AUCs and chimerism rates, associations between busulfan AUCs and incidence of hepatic SOS, differences in clinical outcomes, and associations between chimerism rates and clinical outcomes between BuCy and FluBu. Differences in donor chimerism rates between the two groups were assessed using Student’s t-test, while differences in SOS were assessed using Fisher’s exact test. Linear regression was used to evaluate associations between busulfan AUCs and donor chimerism rates. Log-rank and Cox Proportional Hazards testing were used to perform all time-to-event survival analyses.
Results: Pending
Discussion: Pending
References (must also be included in final poster): References not included per HOPA website. https://www.hoparx.org/documents/169/HOPA_Abstract_Submission_Criteria_2023.pdf
