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2115 A Retrospective Study of C5b-9 and MASP2 Deposition in Skin Microvasculature As a Prognostic and Diagnostic Tool for Transplant-Associated Thrombotic Microangiopathy

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Diseases, Technology and Procedures, Human, Pathology
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Michael Daunov, DO1, John Sumodi2*, Nikki Agarwal, MD1*, Molly Megan Gallogly, MD, PhD1,3, Leland Metheny, MD1,3, Ben K. Tomlinson, MD1,3, Rebecca B. Klisovic, MD1,4, Ali W. Bseiso, MD1*, Brett Glotzbecker, MD1*, Kord Honda5* and Koen van Besien, MD, PhD1,3

1Department of Hematology and Stem Cell Transplant, University Hospitals Seidman Cancer Center, Cleveland, OH
2Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH
3Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH
4Case Western Reserve University, Cleveland, OH
5Department of Dermatopathology, University Hospitals, Cleveland, OH

Introduction

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but serious complication of stem cell transplantation (SCT) which presents an urgent and life-threatening diagnostic dilemma. Skin biopsies with detectable deposition of terminal complement component C5b-9 and lectin pathway of complement enzyme mannose-binding lectin–associated serine protease 2 (MASP2) have been described in small cohorts of TA-TMA patients as correlating with a clinical diagnosis of TA-TMA. We sought to verify the role of skin microvasculature with C5b-9 and MASP2 deposition as a diagnostic tool, assess its specificity for TA-TMA in the setting of Graft vs Host Disease (GVHD), and examine its predictive role differentiation standard vs high-risk TA-TMA.

Methods

We identified patients who had undergone alloSCT and had had skin biopsies for various reasons. Data regarding diagnostic criteria for TA-TMA and GVHD were collected and three cohorts were identified: those with suspected TA-TMA, those without TA-TMA but with histological evidence of GVHD, and those without either TA-TMA or GVHD. Skin biopsies were evaluated by IHC for C5b-9 and MASP2 and read by a dermatopathologist blinded to their TA-TMA status. C5b-9 and MASP2 deposition in skin biopsies were tabulated and comparison between groups was performed using chi-squared analysis.

Results

We identified 30 patients: 9 with confirmed or suspected TA-TMA, 13 with histological evidence of GVHD, and 8 without GVHD or TA-TMA. Half (50%) of the 8 control cases stained positive for C5b-9 or MASP2. Of the 13 cases with histological evidence of GVHD, 5 (21%) stained positive for either C5b-9 or MASP2. Of the 9 patients with confirmed or suspected TA-TMA, 4 met modified Jodele criteria for TA-TMA, 4 had incomplete evaluations or did not meet diagnostic criteria, and 1 met criteria but had skin biopsy 4 months after diagnosis. Three of 4 patients (75%) with confirmed TA-TMA stained positive for C5b-9 or MASP2 which was not statistically significant relative to the GVHD cohort; χ2=0.53, p=.468, or the control cohort; χ2=0.1723, p=.68. All of the cases that met criteria for high-risk TA-TMA (n=3) stained positive for C5b-9 or MASP2 while the one patient with standard risk TA-TMA did not stain positive for C5b-9 or MASP2. Three of 4 (75%) patients with suspected TA-TMA stained positive for C5b-9 or MASP2. One patient who had TA-TMA four months prior did not stain positive for either C5b-9 or MASP2.

Conclusions

In this retrospective evaluation of skin biopsies for patients who had undergone alloSCT with suspected TA-TMA or GVHD, C5b-9 and MASP2 deposition in skin microvasculature was not correlated with clinical diagnosis of TA-TMA as defined by the modified Jodele criteria, albeit with small numbers. Patients with high-risk disease had more staining of C5b-9 and MASP2 vs standard risk TA-TMA but this was not statistically significant. We could not confirm initial reports of C5b-9 or MASP2 in skin microvasculature as a diagnostic tool for TA-TMA. In our hands, the assay lacks sensitivity and specificity.

Disclosures: Metheny: Taiho: Speakers Bureau; Incyte: Speakers Bureau. Tomlinson: BMS: Consultancy, Research Funding. van Besien: Intellia: Consultancy; Avertix: Current equity holder in private company; Autolus: Consultancy; Hemogenyx: Consultancy, Current equity holder in publicly-traded company; Adbio: Consultancy; ADC Therapeutics: Consultancy; Realta: Consultancy; INCYTE: Consultancy; SNIPR Microbiome: Consultancy; Morphosys: Consultancy; Astra Zeneca: Consultancy.

*signifies non-member of ASH