Granulocyte transfusion during cord blood transplant for relapsed, refractory <scp>AML</scp> is associated with massive <scp>CD8</scp><sup>+</sup> T‐cell expansion, significant cytokine release syndrome and induction of disease remission
Roisin Borrill, Kay Poulton, Laura Kusyk, Amy Routledge, Denise Bonney, Ramya Hanasoge‐Nataraj, Madeleine Powys, Omima Mustafa, Helen Campbell, Srividhya Senthil, Richard Dillon, Jelena Jovanović, Suzy Morton, Beki James, Kanchan Rao, Simon Stanworth, Joanne E. Konkel, Robert Wynn
Abstract
Summary In high‐risk myeloid malignancy, relapse is reduced using cord blood transplant (CBT) but remains the principal cause of treatment failure. We previously described T‐cell expansion in CBT recipients receiving granulocyte transfusions. We now report the safety and tolerability of such transfusions, T‐cell expansion data, immunophenotype, cytokine profiles and clinical response in children with post‐transplant relapsed acute leukaemia who received T‐replete, HLA‐mismatched CBT and pooled granulocytes within a phase I/II trial (ClinicalTrials.Gov NCT05425043). All patients received the transfusion schedule without significant clinical toxicity. Nine of ten patients treated had detectable measurable residual disease (MRD) pre‐transplant. Nine patients achieved haematological remission, and eight became MRD negative. There were five deaths: transplant complications ( n = 2), disease ( n = 3), including two late relapses. Five patients are alive and in remission with 12.7 months median follow up. Significant T‐cell expansion occurred in nine patients with a greater median lymphocyte count than a historical cohort between days 7–13 (median 1.73 × 10 9 /L vs. 0.1 × 10 9 /L; p < 0.0001). Expanded T‐cells were predominantly CD8 + and effector memory or TEMRA phenotype. They exhibited markers of activation and cytotoxicity with interferon‐gamma production. All patients developed grade 1–3 cytokine release syndrome (CRS) with elevated serum IL‐6 and interferon‐gamma.