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Interaction Between High-Dose Intravenous Busulfan and Post-Transplantation Cyclophosphamide on Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplantation

2023; Elsevier BV; Volume: 29; Issue: 9 Linguagem: Inglês

10.1016/j.jtct.2023.07.007

2666-6367

Abel Santos Carreira, María Queralt Salas, Mats Remberger, Igor Novitzky‐Basso, Arjun Law, Wilson Lam, Ivan Pašić, Tony Mazzulli, Christine Cserti‐Gazdewich, Dennis Dong Hwan Kim, Fotios V. Michelis, Auro Viswabandya, Armin Gerbitz, Jeffrey H. Lipton, Rajat Kumar, Moustapha Hassan, Jonas Mattsson,

Adolescent and Pediatric Healthcare

This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo- hematopoietic stem cell transplantation. Two hundred fifty-two (26.5%) patients received myeloablative conditioning regimens, and 81.4% received high-dose intravenous busulfan (HD Bu). Six hundred ninety-five (72.4%) patients received post-transplantation cyclophosphamide (PTCY)–based prophylaxis, and 91.4% additionally received anti-thymocyte globulin (ATG) and Cyclosporine A (CsA) (PTCY-ATG-CsA). Two hundred twenty-eight (23.8%) patients developed HC. The day 100 cumulative incidences of grades 2–4 and 3–4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2–4 HC (hazard ratio [HR] = 1.97, P = .035), and HD BU combined with ATG-PTCY-CsA increased this 4 times (HR = 4.06, P < .001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV acute graft-versus-host disease and grade 2-4 HC (HR = 2.10, P < .001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year overall survival (HR = 1.51, P = .009) and higher non-relapse mortality (HR = 2.31, P < .001), and patients with BK-NEG grade 2-4 HC had comparable post-transplantation outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2–4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased 4-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory because its presence significantly increases the risk for mortality.