XGBoost-SHAP Interpretable Modeling Identifies and Validates an Eight-Gene Biomarker for Hepatic Encephalopathy Risk Prediction in Cirrhosis.

In the post-transplant cyclophosphamide (PTCy)-based allogeneic hematopoietic cell transplantation (alloHCT) platform, donor stem cells and mature immune cells are given without immunosuppression, allowing for an inflammatory cascade to begin prior to the administration of PTCy on days +3 and +4. During this window of time without immunosuppression, patients may develop a cytokine release syndrome (CRS)-like inflammatory response, manifesting with fevers and sometimes hypotension and hypoxia. This pre-PTCy hyperinflammatory state is thought to be driven by donor T cell activation, similar to T cell-mediated CRS observed in autologous chimeric antigen receptor (CAR) T cell therapy []. However, more severe inflammatory toxicities classically associated with CAR T-cell therapy, including hemophagocytic lymphohistiocytosis (HLH) and immune effector cell-associated neurotoxicity syndrome (ICANS), are less well described after alloHCT. We report two illustrative cases that highlight the importance of early recognition and prompt immunosuppressive therapy to mitigate potentially life-threatening hyperinflammation. Such cases are important to report, as there are currently no validated diagnostic criteria or well-established treatment paradigms for these clinical scenarios. A man in his late-50s with myelodysplastic syndrome/myeloproliferative neoplasm with fibrosis (del(5q), KMT2A mutation) underwent a 7/10 human leukocyte antigen (HLA)-mismatched unrelated donor alloHCT with thiotepa/busulfan/fludarabine conditioning and dose-reduced PTCy (35 mg/kg) for graft-versus-host disease prophylaxis. His history included prior human immunodeficiency virus infection with undetectable viral load on combination bictegravir, emtricitabine, and tenofovir, coronary artery disease, hypertension, stage 3 chronic kidney disease, and type 2 diabetes. On day +1, he developed fever (39.1°C), fatigue, and tachycardia (grade 1 CRS), with persistent high fevers over the next 48 hours followed by acute kidney injury, metabolic acidosis, oliguria, hyponatremia, hyperbilirubinemia, and progression to hypoxic respiratory failure requiring bilevel positive airway pressure (grade 4 CRS). Infectious workup (blood and urine cultures, Clostridioides difficile testing) was negative. He also developed a type 2 non-ST elevation myocardial infarction requiring nitroglycerin infusion.