(151) Incidence and Association of Prolonged Cytopenias with Severe Cytokine Release Syndrome Among Patients Undergoing PTCy-Based Haploidentical Stem Cell Transplantation: An Urban Medical Center Analysis

Poster Abstract: Background/Rationale:
Allogenic hematopoietic stem-cell transplant (Allo-HSCT) is a curative strategy for patients with many hematologic and non-hematologic disorders. While HLA-matched donor transplants are associated with optimal transplant-related outcomes, the scarcity of HLA-matched donors necessitates alternatives for racially and ethnically diverse patients. The use of post-transplant cyclophosphamide (PTCy) after T-cell replete haploidentical HSCT has resulted in graft versus host disease (GVHD) rates comparable to those of fully matched transplants, and therefore has enabled the safe and widespread use of transplant when an HLA-matched donor is unavailable.

Cytokine release syndrome (CRS) is a common occurrence after haplo-HSCT. CRS, characterized by fevers, hypotension, and oxygen desaturation, is associated with an increase in cytokines IFN-γ, IL-6, and TNF-α. While CRS can impact short term outcomes, its impact on long term outcomes after haplo-HSCT is unknown.

Prolonged cytopenias leading to life-threatening infections and transfusion dependence, occurs after haplo-HSCT, with TNF-α being implicated as a mediator of impaired stem cell function and differentiation. To that end, the impact of severe CRS on the incidence of prolonged cytopenias is unknown.

Objectives:
1. Characterize the incidence of prolonged (>180 days) post-transplant cytopenias after PTCy-based haplo-HSCT.

2. Determine the association between ASTCT Grade 3 and 4 CRS and prolonged cytopenias (using NCI-CTCAE v. 5.0 grading)

Methods:
A single-center retrospective chart review of 72 consecutive patients who underwent haplo-HSCT with PTCy at UI Health from March 2012 to August 2023 was conducted. This study analyzes the association between severe CRS and post-transplant cytopenias. CRS will be graded based on ASTCT consensus grading which accounts for the presence of fever (>38°C) along with the severity of hypoxia and/or hypotension. Grade 3 or 4 cytopenias will be defined as the need for a transfusion within 6 months of the haplo-HSCT. Secondary endpoints include the comparison of acute and chronic GVHD, donor chimerism, non-relapse mortality, and overall survival in patients with and without cytopenias. Comparative and regression statistical analyses were applied to clinical data. A multivariate model adjusted for established prognostic factors will be done to determine if CRS independently predicts for prolonged cytopenias.

Results:
Data collection and analysis is in process.

Conclusions/

Discussion:
Findings are pending upon completion of data analysis.

References (must also be included in final poster): 1. Szydlo R, Goldman JM, Klein JP, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15:1767–1777.
2. Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641-650.
3. McCurdy SR, Kanakry JA, Showel MM, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125(19):3024-3031.
4. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–195.