Low utility of the H-Score and HLH-2004 criteria to identify patients with secondary hemophagocytic lymphohistiocytosis after CAR-T cell therapy for relapsed/refractory diffuse large B-Cell lymphoma

Leuk Lymphoma. 2022 Jun;63(6):1339-1347. doi: 10.1080/10428194.2021.2024817. Epub 2022 Jan 19.

Abstract

Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation disorder. Use of chimeric antigen receptor T-cell therapy (CAR-T) is associated with cytokine release syndrome (CRS), Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) and secondary HLH. However, application of HLH scoring systems (H-score, HLH-2004 criteria) are not validated in this setting. We analyzed the utility of applying the H-score and the HLH-2004 criteria to identify patients with possible HLH post-CAR-T for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Only two of four patients with post CAR-T HLH met five or more of the diagnostic criteria for HLH by HLH 2004 criteria. In contrast all four post CAR-T HLH patients had a high H-score (>169); however, an additional ten patients that did not have HLH also had a high H-score. Thus, in this patient population, both scoring systems were demonstrated to have low prognostic significance in differentiating between high grade CRS and HLH.

Keywords: CAR-T; DLBCL; HLH; Immunotherapeutic approaches.

MeSH terms

  • Cytokine Release Syndrome
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphohistiocytosis, Hemophagocytic* / diagnosis
  • Lymphohistiocytosis, Hemophagocytic* / etiology
  • Lymphohistiocytosis, Hemophagocytic* / therapy
  • Lymphoma, Large B-Cell, Diffuse* / therapy
  • Receptors, Chimeric Antigen*
  • Recurrence

Substances

  • Receptors, Chimeric Antigen