Influence of ATLG serum levels on CD3/CD19-depleted hematopoietic grafts and on immune recovery in pediatric haplo-HSCT

Claus-Philipp Maier, Chihab Klose, Christian Martin Seitz, Florian Heubach, Michaela Döring, Roland Meisel, Friedhelm Schuster, Bernd Gruhn, Frieder Keller, Armin Rabsteyn, Anne-Marie Arendt, Germano Amorelli, Thomas Eichholz, Tobias Feuchtinger, Holger Martinius, Stefan Nierkens, Rouwen Teltschik, Johannes Hubertus Schulte, Claudia Lengerke, Rupert HandgretingerPeter Lang

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review


Anti-T lymphocyte globulin (ATLG) significantly reduces the risk of engraftment failure in allogeneic hematopoietic stem cell transplant (HSCT) but hampers posttransplant immune reconstitution. We hypothesized that in patients receiving haploidentical CD3/CD19-depleted grafts, these double-edged effects could be better balanced by attaining high ATLG serum concentrations before transplant but as low as possible on the day of transplant. Therefore, we moved the start of ATLG application to day -12 and determined serum concentrations of T-cell-specific ATLG in pediatric patients treated with 3 established dosing regimens (15, 30, or 60 mg/kg). Corresponding mean T-cell-specific ATLG serum concentrations at day 0 were 1.14, 2.99, or 12.10 μg/mL, respectively. Higher ATLG doses correlated with higher peak levels at days -8 and -7 and reduced graft rejection, whereas lower ATLG doses correlated with significantly faster posttransplant recovery of T and natural killer cells. The rate of graft-versus-host disease remained low, independent of ATLG doses. Moreover, in vitro assays showed that ATLG concentrations of 2.0 μg/mL and lower only slightly reduced the activity of natural killer cells, and therefore, the function of such effector cells might be preserved in the grafts. Pharmacokinetic analysis, compatible with linear first-order kinetics, revealed similar half-life values, independent of ATLG doses. Hence, the day on which a desired ATLG serum level is reached can be calculated before HSCT. Our retrospective study demonstrates the relevance of dosing and time of administration of ATLG on engraftment and immune recovery in ex vivo CD3/CD19-depleted haploidentical HSCT.

Originele taal-2Engels
Pagina's (van-tot)2160-2171
Aantal pagina's12
TijdschriftBlood advances
Nummer van het tijdschrift9
StatusGepubliceerd - 14 mei 2024


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