Histone deacetylase inhibitors (HDACi) are active agents for peripheral T-cell lymphoma (PTCL). Anecdotally angioimmunoblastic T-cell lymphoma (AITL) appears to respond better than PTCL–not otherwise specified (NOS) to HDACi. The new World Health Organization classification shows that a subgroup of PTCL carries similarities in phenotype and gene expression profiling to AITL, comparable to T follicular helper (TFH) cells. The disease might behave similarly to AITL when treated with HDACi. We analyzed 127 patients with AITL or PTCL-NOS treated with HDACi at relapse as a single agent or in combination. We re-reviewed the pathology of all PTCL-NOS to identify the TFH phenotype. Patients received HDACi at relapse as a single agent in 97 cases (76%, 59 TFH, 38 non-TFH) or in combination in 30 cases (24%, 18 TFH, 12 non-TFH) including duvelisib, lenalidomide, lenalidomide plus carfilzomib, and pralatrexate. Seven PTCL-NOS had TFH phenotype; 2 PTCL-NOS were reclassified as AITL. Overall response rate (ORR) was 56.5% (28.9% complete response [CR]) in TFH and 29.4% (19.6% CR) in non-TFH phenotype patients (P = .0035), with TFH phenotype being an independent predictor of ORR (P = .009). Sixteen patients sufficiently responded to HDACi or HDACi in combination with another agent to proceed directly to allogeneic transplantation; 1 of 16 responded to donor lymphocyte infusion (12 TFH, 4 non-TFH). Our results, although retrospective, support that HDACi, as a single agent or in combination, may have superior activity in TFH-PTCL compared with non-TFH PTCL. This differential efficacy could help inform subtype-specific therapy and guide interpretation of HDACi trials.

Background Heparin‐induced thrombocytopenia (HIT) is a prothrombotic, immune‐mediated adverse drug reaction associated with high rates of thrombosis‐related morbidity and mortality caused by FcγRIIa‐activating pathogenic antibodies to PF4‐heparin. Procoagulant platelets are a platelet subset that promote thrombin generation, are clinically relevant in prothrombotic diseases, and are formed when platelet G‐protein‐coupled receptor (GPCR) and ITAM‐linked receptors are co‐stimulated. Objectives We examined the procoagulant platelet response of healthy donors to platelet agonists in the presence of HIT plasma and determined the contribution of FcγRIIa. Patients/Methods Our previously established flow cytometry‐based procoagulant platelet assay was modified to incorporate plasma samples, performed using FcγRIIa‐responsive donor platelets. Plasma samples were serotonin‐release assay–confirmed HIT (HIT+), or negative on HIT screening. Results In response to GPCR stimulation, only HIT+ plasma produced a heparin‐dependent sensitization that required active FcγRIIa. As a potential diagnostic tool, the procoagulant platelet assay achieved 98% accuracy in identifying clinically verified HIT when performed blinded to the diagnoses of a validation cohort. Samples inducing a higher procoagulant platelet response were more likely from patients with thrombotic complications. Thrombin stimulation markedly increased the procoagulant platelet response with HIT+ plasma that was heparin independent and only partially reversed by FcγRIIa blockade, possibly reflecting ongoing thrombotic risk after heparin cessation. Conclusions We demonstrate that HIT plasma together with platelet agonists increased the procoagulant platelet proportions, which may contribute to thrombotic risk in HIT. Targeting procoagulant platelet activation may represent a novel treatment strategy. This assay may be a rapid, clinically relevant functional assay for accurately detecting pathological HIT antibodies.

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