识别、定义和管理 CAR-T 血液学毒性

Autologous CAR-T cell therapy (CAR-T) has improved outcomes for patients with B-cell malignancies. It is associated with the well-described canonical toxicities cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which may be abrogated by corticosteroids and the anti-IL6 receptor antagonist tocilizumab. Practitioners and researchers should be aware of additional toxicities.

Here we review current understanding and management of hematologic toxicities after CAR-T, including cytopenias, coagulopathies, bleeding and clotting events, hemophagocytic-lymphohistiocytosis, and tumor lysis syndrome.

We pay particular attention to cytopenias, recently termed immune effector cell-associated hematological toxicity (ICAHT). While the "H" is silent, hematotoxicity is not: ICAHT has the highest cumulative incidence of all immune adverse events following CAR-T. Early cytopenia (day 0-30) is closely linked to lymphodepleting chemotherapy and CRS-related inflammatory stressors. Late ICAHT (after day 30) can present either with or without antecedent count recovery (e. g. , "intermittent" vs "aplastic" phenotype), and requires careful evaluation and management strategies. Growth factor support is the mainstay of treatment, with recent evidence demonstrating safety and feasibility of early granulocyte colony-stimulating factor (G-CSF) (e.

g. , within week 1). In G-CSF refractory cases, autologous stem cell boosts represent a promising treatment avenue, if available. The CAR-HEMATOTOX scoring system, validated for use across lymphoid malignancies (B-NHL, multiple myeloma), enables pretherapeutic risk assessment and presents the potential for risk-adapted management.

Recent expert panels have led to diagnostic scoring criteria, severity grading systems, and management strategies for both ICAHT and the recently termed immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), now clarified and defined as a distinct entity from CRS.