T-cell tracking, safety, and effect of low-dose donor memory T-cell infusions after alpha beta T cell-depleted hematopoietic stem cell transplantation

Sergey Blagov, Ivan V. Zvyagin, Larisa Shelikhova, Rimma Khismatullina, Dmitriy Balashov, Ekaterina Komech, Viktoria Fomchenkova, Mikhail Shugay, Julia Starichkova, Elena Kurnikova, Dmitriy Pershin, Maria Fadeeva, Svetlana Glushkova, Yakov Muzalevskii, Alexei Kazachenok, Maria Efimenko, Elena Osipova, Galina Novichkova, Dmitriy Chudakov, Alexei MaschanMichael Maschan

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts. A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 103 to 100 × 103/kg (haplo) and from 100 × 103 to 300 × 103 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire. In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.

Original languageEnglish
Pages (from-to)900-908
Number of pages9
JournalBone Marrow Transplantation
Volume56
Issue number4
DOIs
Publication statusPublished - Apr 2021

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