Joint modeling of immune reconstitution post haploidentical stem cell transplantation in pediatric patients with acute leukemia comparing CD34+-selected to CD3/CD19-depleted grafts in a retrospective multicenter study

  • Rapid immune reconstitution (IR) following stem cell transplantation (SCT) is essential for a favorable outcome. The optimization of graft composition should not only enable a sufficient IR but also improve graft vs. leukemia/tumor effects, overcome infectious complications and, finally, improve patient survival. Especially in haploidentical SCT, the optimization of graft composition is controversial. Therefore, we analyzed the influence of graft manipulation on IR in 40 patients with acute leukemia in remission. We examined the cell recovery post haploidentical SCT in patients receiving a CD34+-selected or CD3/CD19-depleted graft, considering the applied conditioning regimen. We used joint model analysis for overall survival (OS) and analyzed the dynamics of age-adjusted leukocytes; lymphocytes; monocytes; CD3+, CD3+CD4+, and CD3+CD8+ T cells; natural killer (NK) cells; and B cells over the course of time after SCT. Lymphocytes, NK cells, and B cells expanded more rapidly after SCT with CD34+-selected grafts (P = 0.036, P = 0.002, and P < 0.001, respectively). Contrarily, CD3+CD4+ helper T cells recovered delayer in the CD34 selected group (P = 0.026). Furthermore, reduced intensity conditioning facilitated faster immune recovery of lymphocytes and T cells and their subsets (P < 0.001). However, the immune recovery for NK cells and B cells was comparable for patients who received reduced-intensity or full preparative regimens. Dynamics of all cell types had a significant influence on OS, which did not differ between patients receiving CD34+-selected and those receiving CD3/CD19-depleted grafts. In conclusion, cell reconstitution dynamics showed complex diversity with regard to the graft manufacturing procedure and conditioning regimen.

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Author:Emilia Salzmann-Manrique, Melanie BremmGND, Sabine HüneckeGND, Milena Stech, Andreas Orth, Matthias Eyrich, Ansgar SchulzORCiDGND, Ruth Esser, Thomas KlingebielORCiDGND, Peter BaderORCiDGND, Eva HerrmannORCiD, Ulrike Köhl
Pubmed Id:
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Aurore Saudemont
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/08/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/10/25
Tag:CD3/19 depletion; CD34 selection; allogeneic stem cell transplantation; children; immune reconstitution
Issue:Art. 1841
Page Number:12
First Page:1
Last Page:12
Copyright: © 2018 Salzmann-Manrique, Bremm, Huenecke, Stech, Orth, Eyrich, Schulz, Esser, Klingebiel, Bader, Herrmann and Koehl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0