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 pat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01841/full |
| _version_ | 1811259218647318528 |
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| author | Emilia Salzmann-Manrique Emilia Salzmann-Manrique Melanie Bremm Sabine Huenecke Milena Stech Andreas Orth Matthias Eyrich Ansgar Schulz Ruth Esser Thomas Klingebiel Peter Bader Eva Herrmann Ulrike Koehl Ulrike Koehl Ulrike Koehl |
| author_facet | Emilia Salzmann-Manrique Emilia Salzmann-Manrique Melanie Bremm Sabine Huenecke Milena Stech Andreas Orth Matthias Eyrich Ansgar Schulz Ruth Esser Thomas Klingebiel Peter Bader Eva Herrmann Ulrike Koehl Ulrike Koehl Ulrike Koehl |
| author_sort | Emilia Salzmann-Manrique |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T18:27:14Z |
| format | Article |
| id | doaj.art-5e424022dafd4153adc10b37c79f4510 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T18:27:14Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5e424022dafd4153adc10b37c79f45102022-12-22T03:21:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01841365086Joint 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 StudyEmilia Salzmann-Manrique0Emilia Salzmann-Manrique1Melanie Bremm2Sabine Huenecke3Milena Stech4Andreas Orth5Matthias Eyrich6Ansgar Schulz7Ruth Esser8Thomas Klingebiel9Peter Bader10Eva Herrmann11Ulrike Koehl12Ulrike Koehl13Ulrike Koehl14Department of Medicine, Institute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe-University, Frankfurt, GermanyPediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, GermanyPediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, GermanyPediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, GermanyPediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, GermanyUniversity of Applied Sciences Frankfurt, Frankfurt, GermanyPediatric Hematology and Oncology, University of Wuerzburg, Wuerzburg, GermanyPediatric Hematology and Oncology, University of Ulm, Ulm, GermanyInstitute of Cellular Therapeutics Hannover Medical School, Hannover, GermanyPediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, GermanyPediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Frankfurt, GermanyDepartment of Medicine, Institute of Biostatistics and Mathematical Modeling, Johann Wolfgang Goethe-University, Frankfurt, GermanyInstitute of Cellular Therapeutics Hannover Medical School, Hannover, GermanyInstitute of Clinical Immunology, University of Leipzig, Leipzig, GermanyFraunhofer Institute of Cellular Therapy and Immunology, Leipzig, GermanyRapid 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.01841/fullimmune reconstitutionallogeneic stem cell transplantationCD34 selectionCD3/19 depletionchildren |
| spellingShingle | Emilia Salzmann-Manrique Emilia Salzmann-Manrique Melanie Bremm Sabine Huenecke Milena Stech Andreas Orth Matthias Eyrich Ansgar Schulz Ruth Esser Thomas Klingebiel Peter Bader Eva Herrmann Ulrike Koehl Ulrike Koehl Ulrike Koehl 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 Frontiers in Immunology immune reconstitution allogeneic stem cell transplantation CD34 selection CD3/19 depletion children |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | immune reconstitution allogeneic stem cell transplantation CD34 selection CD3/19 depletion children |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01841/full |
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