Hemorrhagic Cystitis in Patients Undergoing Allogeneic Hematopoietic Cell Transplant with Post Transplant Cyclophosphamide As GvHD Prophylaxis

The use of post-transplant cyclophosphamide (PTCy) as graft-versus-host-disease (GvHD) prophylaxis after hematopoietic cell transplantation (HCT) has increased significantly over the past decade due to expansion of donor pool with haploidentical and mismatched unrelated donors. A recently completed phase 2 study, PROGRESS-2 (NCT02345850), has highlighted the efficacy of PTCy in the matched donor setting. Hemorrhagic cystitis (HC) is the most notable toxicity associated with high dose Cy. However, data specific to the incidence and severity of HC in the post HCT setting is sparse, with no consensus on best practices to prevent HC in patients receiving PTCy. Current strategies to prevent HC in PTCy setting have been adapted from data in pre-HCT Cy (conditioning setting), such as hyperhydration with forced diuresis, continuous bladder irrigation, mesna as an intermittent and continuous infusion, or a combination of these methods. The aim of our study was to describe the incidence and severity of HC in patients undergoing HCT with PTCy as GvHD prophylaxis, identifying potential risk factors and impact of HC on HCT outcomes. We retrospectively reviewed 194 consecutive patients who underwent their first HCT with PTCy from 2014 to 2018 at our center. More than half of the patients (53%) received myeloablative conditioning regimen with majority receiving peripheral blood stem cells (81%) from haploidentical donors (96%). GvHD prophylaxis was unified with PTCy (50 mg/kg on Days +3 and +4), in addition to MMF (1 gm 3x daily starting on Day +5) and tacrolimus (1 mg as a continuous infusion daily starting on Day +5). Standard HC prophylaxis was hyperhydration with forced diuresis and mesna at 320% the daily dose of PTCy. Incidence of HC was based on physician documentation or presence of blood in urinalysis up to Day +100. To determine severity of HC, CTCAE 5.0 grading system was used. Median age of patients was 45 years (range: 2-73), with 60% of patients being male. KPS was ≥80% in 83% of patient and 40% had HCT-CI of ≥2. The most common diagnoses included: AML (41%), ALL (24%) and MDS/MPN (19%). There were 55 patients who received ≥3 lines of therapy, 116 patients received In conclusion, hyperhydration with forced diuresis added to aggressive mesna dosing is an effective strategy in preventing severe HC in HCT patients receiving PTCy as GvHD prophylaxis. Incidence of Grade 3 or 4 HC was low and transient and did not impact HCT outcomes. Viral HC had a significantly later onset than non-viral HC, suggesting a different pathophysiology. Older age and myeloablative conditioning were independent factors for higher incidence of HC in our cohort. Download : Download high-res image (410KB) Download : Download full-size image Disclosures Ali: Incyte Corporation: Consultancy. Salhotra: Celgene: Research Funding; Kadmon: Membership on an entity's Board of Directors or advisory committees. Aribi: Seattle Genetics: Consultancy. Pullarkat: Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stein: Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Marcucci: Merck: Other: Research Support (Investigation Initiated Clinical Trial); Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Iaso Bio: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Research Support (Investigation Initiated Clinical Trial). Nakamura: NapaJen Pharma: Consultancy; Viracor: Consultancy; Kadmon Corporation: Other: Advisory board meeting; Magenta Therapeutics: Other: Advisory board meeting; Celgene: Other: Support on seminar; Kyowa-Kirin: Other: Support on a meeting presentation; Alexion: Other: Support on a meeting presentation; Merck: Other: advisory board meeting. Al Malki: Rigel Pharma: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Neximmune: Consultancy.