(109) Evaluation of Risk Factors and Outcomes of Hemorrhagic Cystitis Following Allogeneic Hematopoietic Cell Transplant with Post-Transplant Cyclophosphamide

Poster Abstract: Presenter: Kyle Gash, PharmD, Moffitt Cancer Center, Tampa, FL

Co-Authors: Timothy J. Porter, PharmD, BCOP, Moffitt Cancer Center, Tampa, FL; Samantha Price, PharmD, BCOP, Moffitt Cancer Center, Tampa, FL; Hany Elmariah, MD, MS, Moffitt Cancer Center, Tampa, FL

Background: Post-transplant cyclophosphamide (PTCy) prophylaxis regimens reduce incidence of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplant (HCT). However, the management of complications associated with PTCy, specifically hemorrhagic cystitis caused by the buildup of acrolein in the bladder urothelium, is also critical to ensure successful allogeneic HCT outcomes. Strategies for preventing cyclophosphamide-induced hemorrhagic cystitis include hyperhydration with forced diuresis and the use of mesna. However, optimal strategies for hemorrhagic cystitis prevention remain to be elucidated.

Objectives: To identify risk factors that may increase incidence of hemorrhagic cystitis and evaluate the efficacy and safety of IV fluid hydration with forced diuresis and IV bolus mesna in patients who underwent allogeneic HCT and received PTCy.

Methods: Retrospective chart review of adult patients who underwent allogeneic HCT and received PTCy-based GVHD prophylaxis at Moffitt Cancer Center between March 1, 2019, and May 31, 2023. Patients excluded were the following: received a prior autologous or allogeneic HCT or started immunosuppression prior to the start of PTCy. The primary objective is to assess the incidence of early hemorrhagic cystitis, defined as documentation of clinical signs/symptoms of cystitis that met one of the following criteria: documentation of dysuria and lower abdominal pain; the presence of hematuria grade 2 or higher with negative urine culture for bacteria or fungus in the absence of any other clinical explanation; and occurred within 7 days after the start of PTCy. Secondary objectives include the following: incidence of late hemorrhagic cystitis up to Day +100; acute kidney injury grade 2 or higher within 7 days after PTCy; pulmonary complications within 7 days after PTCy; viral reactivation of BK polyomavirus, JC virus, adenovirus, or cytomegalovirus up to Day +100; and all-cause mortality at Day +30 and Day +100.

Results: Pending

Conclusion: Pending

References (must also be included in final poster): 1. Imus, Philip H., et al. “Severe Cytokine Release Syndrome after Haploidentical Peripheral Blood Stem Cell Transplantation.” Biol Blood Marrow Transplant. 2019 Dec;25(12):2431-2437.
2. O’Donnell, Paul V., and Jones, Richard J. “The Development of Post-Transplant Cyclophosphamide: Half a Century of Translational Team Science.” Blood Rev. 2022 Nov 13;101034.
3. Atilla E., et al. “A Review of Myeloablative vs Reduced Intensity/Non-Myeloablative Regimens in Allogeneic Hematopoietic Stem Cell Transplantations.” Balkan Med J. 2017 Jan;34(1):1-9.
4. Bolanos-Meade J., et al. “Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis”. N Engl J Med. 2023 Jun 22;388(25):2338-2348.
5. Jones RJ. “Haploidentical Transplantation: Repurposing Cyclophosphamide. Biol Blood Marrow Transplant.” 2012 Dec;18(12):1771-2.
6. Kanakry C., et al. “Aldehyde Dehydrogenase Expression Drives Human Regulatory T Cell Resistance to Posttransplantation Cyclophosphamide.” Sci Transl Med. 2013 Nov 13;5(211):211ra157.
7. De Jonge M., et al. “Clinical Pharmacokinetics of Cyclophosphamide.” Clin Pharmacokinet. 2005;44(11):1135-64.
8. Matz E., et al. “Review of Advances in Uroprotective Agents for Cyclophosphamide- and Ifosfamide-induced Hemorrhagic Cystitis.” Urology. 2017;100:16-9.
9. Hensley M. et al. “American Society of Clinical Oncology 2008 Clinical Practice Guideline Update: Use of Chemotherapy and Radiation Therapy Protectants.” J Clin Oncol. 2009 Jan;27(1):127-45.
10. Silva L., et al. “Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplants is the Complex Result of BK Virus Infection, Preparative Regimen Intensity and Donor Type.” Haematologica. 2010 Jul;95(7):1183-90.