A prediction model for reactivation of Langerhans cell histiocytosis based on machine-learning algorithms.

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm characterized by the clonal proliferation of myeloid progenitor cells. The reactivation rate of LCH exceeds 30%. However, an effective prediction model to predict reactivation is lacking. To select potential prognostic factors of LCH and construct an easy-to-use predictive model based on machine-learning algorithms. Clinical records of LCH inpatients in the Second Xiangya Hospital of Central South University, from 2008 to 2022, were retrospectively studied. Seventy-six patients were classified into a reactivated/progressive group or a stable group. Clinical features and laboratory outcomes were compared, and machine-learning algorithms were used for building prognostic prediction models. Clinical classification (single-system LCH, multiple-system LCH, and central nervous system/lung LCH), level of anemia, bone involvement, skin involvement, and elevated monocyte count were the best performing factors and were finally chosen for the construction of the prediction models. Our results show that the above-mentioned five factors can be used together in a prediction model for the prognosis of LCH patients. The major limitations of this study include its retrospective nature and the relatively small sample size.

Chimeric antigen receptor T cells self-neutralizing IL6 storm in patients with hematologic malignancy.

IL6 is one of the most elevated cytokines during chimeric antigen receptor (CAR) T cell cytokine release syndrome (CRS), and IL6R blockade by Tocilizumab has successfully relieved the most life-threatening aspects of CRS in patients. In addition, latest studies demonstrated the essential role of IL1 in driving CART induced neurotoxicity in mouse models. Here we present a clinical investigation (ChiCTR2000032124; ChiCTR2000031868) of anti-CD19 and anti-BCMA CART (41BBζ) secreting an anti-IL6 scFv and IL1 receptor antagonist (IL1RA) in treating patients with hematologic malignancy. Our results revealed that IL6 and IL1B were maintained at low levels without significant elevation during CRS, rendering Tocilizumab dispensable. Moreover, treated patients did not show neurotoxicity during CRS and exhibited mild to moderate CRS. Notably, we observed high rate of complete response (CR) and significant CART expansion during treatment. In sum, we conclude that CART-secreting anti-IL6 scFv and IL1RA could self-neutralize IL6 storm and maintain low levels of IL1B during CART therapy to minimize IL6- and IL1-associated cytokine toxicity and neurotoxicity without impairing therapeutic efficacy.