Marion Eveillard

The presence of donor Vγ9Vδ2 T‐cells after haploidentical hematopoietic stem cell transplant (h‐HSCT) has been associated with improved disease‐free survival. These cells kill tumor cells in a non‐MHC restricted manner, do not induce graft‐versus‐host disease (GVHD), and can be generated by stimulation with zoledronic acid (ZA) in combination with interleukin‐2 (IL‐2). This monocentric phase I, open‐label, dose‐escalating study (ClinicalTrials.gov: NCT03862833) aimed at evaluating the safety and possibility to generate Vγ9Vδ2 T‐cells early after h‐HSCT. It applied a standard 3 + 3 protocol to determine the maximum tolerated dose (MTD) of increasing low‐doses of IL‐2 (5 days [d] per week, 4 weeks) in combination with a single dose of ZA, starting both the first Monday after d + 15 posttransplant. Vγ9Vδ2 T‐cell monitoring was performed by multiparameter flow cytometry on blood samples and compared with a control cohort of h‐HSCT recipients. Twenty‐six patients were included between April 2019 and September 2022, 16 of whom being ultimately treated and seven being controls who received h‐HSCT only. At the three dose levels tested, 1, 0, and 1 dose‐limiting toxicities were observed. MTD was not reached. A significantly higher number of Vγ9Vδ2 T‐cells was observed during IL‐2 treatment compared with controls. In conclusion, early in vivo generation of Vγ9Vδ2 T‐cells is feasible after h‐HSCT by using a combination of ZA and repeated IL‐2 infusions. This study paves the way to a future phase 2 study, with the hope to document lesser posttransplant relapse with this particular adaptive immunotherapy.

Background The bleeding risk of patients with mild platelet function disorders is difficult to assess and their phenotype remains ill‐explored. Aim This study was designed to establish a comprehensive biological phenotype of patients with mild platelet function disorders. Methods Twenty patients were included with persistent abnormal light transmission aggregometry (LTA). The ISTH bleeding assessment tool (ISTH‐BAT) was assessed to identify laboratory analyses associated with an abnormal hemorrhagic score. Results The majority of patients had defects that might affect Gαi protein signaling pathways or minor abnormalities. No LTA nor flow cytometry parameters were associated with an above‐normal hemorrhagic score. However, prothrombin consumption, which corresponds to the ratio of serum residual factor II to plasma residual factor II, was significantly higher ( p = .006) in the abnormal ISTH‐BAT group (mean = 14%, SD = 6) compared with the normal ISTH‐BAT group (mean = 8%, SD 4). Prothrombin consumption was significantly associated with ISTH‐BAT score ( r = .5287, IC 95% 0.0986–0.7924, p = .0165). Conclusion In this group of patients, there was an association between a pathological bleeding score and increased prothrombin consumption. This test could be used as an additional indicator of platelet function abnormality liable to be related to bleeding risk.