期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1111/bjh.18863
关键词
cord blood; cord blood transplant; granulocytes; myeloid leukaemia; paediatric haematology
类别
Cord blood transplant (CBT) can reduce relapse in high-risk myeloid malignancy, but it remains a major cause of treatment failure. This study observed the safety and tolerability of granulocyte transfusions in CBT recipients, as well as their T-cell expansion, immunophenotype, cytokine profiles, and clinical responses in children with post-transplant relapsed acute leukemia.
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 x 10(9)/L vs. 0.1 x 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.
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