دورية أكاديمية
Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies.
| العنوان: | Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies. |
|---|---|
| المؤلفون: | Cordón L; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain. lou.cordon@gmail.com.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain. lou.cordon@gmail.com., Chorão P; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Martín-Herreros B; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain., Montoro J; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Balaguer A; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Guerreiro M; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Villalba M; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Facal A; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Asensi P; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Solves P; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Gómez I; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Santiago M; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Lamas B; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Bataller A; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Granados P; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Sempere A; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Sanz GF; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Sanz MA; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Sanz J; Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Avenida Fernando Abril Martorell, 106, Valencia, 46026, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain.; Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain. |
| المصدر: | Annals of hematology [Ann Hematol] 2024 Jul; Vol. 103 (7), pp. 2475-2484. Date of Electronic Publication: 2024 Apr 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9107334 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0584 (Electronic) Linking ISSN: 09395555 NLM ISO Abbreviation: Ann Hematol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Berlin : Springer Verlag Original Publication: Berlin ; New York : Springer International, c1991- |
| مواضيع طبية MeSH: | Transplantation Conditioning*/methods , Hematologic Neoplasms*/therapy , Cord Blood Stem Cell Transplantation*/methods , Antilymphocyte Serum*/therapeutic use , Graft vs Host Disease*/etiology , Graft vs Host Disease*/prevention & control , Immune Reconstitution*, Humans ; Female ; Male ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent ; Killer Cells, Natural/immunology ; Myeloablative Agonists/therapeutic use |
| مستخلص: | This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3 + T cells, CD8 + T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4 + T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4 + T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning. (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
| References: | Szabolcs P, Cairo MS (2010) Unrelated umbilical cord blood transplantation and Immune reconstitution. Semin Hematol 47:22–36. https://doi.org/10.1053/j.seminhematol.2009.10.009. (PMID: 10.1053/j.seminhematol.2009.10.009201096093684393) Elfeky R, Lazareva A, Qasim W, Veys P (2019) Immune reconstitution following hematopoietic stem cell transplantation using different stem cell sources. Expert Rev Clin Immunol 15:735–751. https://doi.org/10.1080/1744666X.2019.1612746. (PMID: 10.1080/1744666X.2019.161274631070946) Thomson BG, Robertson KA, Gowan D, Heilman D, Broxmeyer HE, Emanuel D, Kotylo P, Brahmi Z, Smith FO (2000) Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation. Blood 96:2703–2711. https://doi.org/10.1182/blood.V96.8.2703. (PMID: 10.1182/blood.V96.8.270311023501) Klein AK, Patel DD, Gooding ME, Sempowski GD, Chen BJ, Liu C, Kurtzberg F, Haynes BF, Chao NJ (2001) T-cell recovery in adults and children following umbilical cord blood transplantation. Biol Blood Marrow Transplant 7:454–466. https://doi.org/10.1016/S1083-8791(01)80013-6. (PMID: 10.1016/S1083-8791(01)80013-611569891) Pavletic ZS, Joshi SS, Nasrati K et al (1998) Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies. Bone Marrow Transplant 21:33–41. https://doi.org/10.1038/sj.bmt.1701037. (PMID: 10.1038/sj.bmt.170103794864927101861) Komanduri KV, St. John LS, de Lima M et al (2007) Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing. Blood 110:4543–4551. https://doi.org/10.1182/blood-2007-05-092130. Niehues T, Rocha V, Filipovich AH et al (2001) Factors affecting lymphocyte subset reconstitution after either related or unrelated cord blood transplantation in children a Eurocord analysis. Br J Haematol 114:42–48. https://doi.org/10.1046/j.1365-2141.2001.02900.x. (PMID: 10.1046/j.1365-2141.2001.02900.x11472343) Brahmi Z, Hommel-Berrey G, Smith F, Thomson B (2001) NK cells recover early and mediate cytotoxicity via perforin/granzyme and Fas/FasL pathways in umbilical cord blood recipients. Hum Immunol 62:782–790. https://doi.org/10.1016/S0198-8859(01)00275-0. (PMID: 10.1016/S0198-8859(01)00275-011476901) Moretta A, Maccario R, Fagioli F et al (2001) Analysis of immune reconstitution in children undergoing cord blood transplantation. Exp Hematol 29:371–379. https://doi.org/10.1016/S0301-472X(00)00667-6. (PMID: 10.1016/S0301-472X(00)00667-611274766) de Koning C, Plantinga M, Besseling P, Boelens JJ, Nierkens S (2016) Immune reconstitution after allogeneic hematopoietic cell transplantation in children. Biol Blood Marrow Transplant 22:195–206. https://doi.org/10.1016/j.bbmt.2015.08.028. (PMID: 10.1016/j.bbmt.2015.08.02826341398) Elmariah H, Brunstein CG, Bejanyan N (2021) Immune reconstitution after Haploidentical Donor and umbilical cord blood allogeneic hematopoietic cell transplantation. Life (Basel Switzerland) 11:102. https://doi.org/10.3390/life11020102. (PMID: 10.3390/life1102010233572932) Jacobson CA, Turki AT, McDonough SM et al (2012) Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 18:565–574. https://doi.org/10.1016/j.bbmt.2011.08.018. (PMID: 10.1016/j.bbmt.2011.08.01821875503) Kanda J, Chiou L, Szabolcs P et al (2012) Immune Recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant 18:1664–1676e1. https://doi.org/10.1016/j.bbmt.2012.06.005. (PMID: 10.1016/j.bbmt.2012.06.005226984853472115) Sauter C, Abboud M, Jia X et al (2011) Serious infection risk and Immune Recovery after double-unit cord blood transplantation without Antithymocyte Globulin. Biol Blood Marrow Transplant 17:1460–1471. https://doi.org/10.1016/j.bbmt.2011.02.001. (PMID: 10.1016/j.bbmt.2011.02.001213102543165093) Bejanyan N, Brunstein CG, Cao Q et al (2018) Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD. Blood Adv 2:909–922. https://doi.org/10.1182/bloodadvances.2017014464. (PMID: 10.1182/bloodadvances.2017014464296788095916001) Saliba RM, Rezvani K, Leen A et al (2015) General and Virus-Specific Immune Cell reconstitution after double cord blood transplantation. Biol Blood Marrow Transplant 21:1284–1290. https://doi.org/10.1016/j.bbmt.2015.02.017. (PMID: 10.1016/j.bbmt.2015.02.017257082194798431) Politikos I, Kim HT, Nikiforow S, Li L, Brown J, Antin JH, Cutler C, Ballen K, Ritz J, Boussiotis VA (2015) IL-7 and SCF levels inversely correlate with T cell reconstitution and clinical outcomes after cord blood transplantation in adults. PLoS ONE 10:e0132564. https://doi.org/10.1371/journal.pone.0132564. (PMID: 10.1371/journal.pone.0132564261775514503696) Lindemans CA, Chiesa R, Amrolia PJ et al (2014) Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood 123:126–132. https://doi.org/10.1182/blood-2013-05-502385. (PMID: 10.1182/blood-2013-05-50238524184682) Admiraal R, Lindemans CA, van Kesteren C, Bierings MB, Versluijs AB, Nierkens S, Boelens JJ (2016) Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation. Blood 128:2734–2741. https://doi.org/10.1182/blood-2016-06-721936. (PMID: 10.1182/blood-2016-06-72193627702800) Chiesa R, Gilmour K, Qasim W et al (2012) Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4 + cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol 156:656–666. https://doi.org/10.1111/j.1365-2141.2011.08994.x. (PMID: 10.1111/j.1365-2141.2011.08994.x22224700) Hiwarkar P, Hubank M, Qasim W, Chiesa R, Gilmour KC, Saudemont A, Amrolia PJ, Veys P (2017) Cord blood transplantation recapitulates fetal ontogeny with a distinct molecular signature that supports CD4 + T-cell reconstitution. Blood Adv 1:2206–2216. https://doi.org/10.1182/bloodadvances.2017010827. (PMID: 10.1182/bloodadvances.2017010827292968685737134) de Koning C, Gabelich J, Langenhorst J, Admiraal R, Kuball J, Boelens JJ, Nierkens S (2018) Filgrastim enhances T-cell clearance by antithymocyte globulin exposure after unrelated cord blood transplantation. Blood Adv 2:565–574. https://doi.org/10.1182/bloodadvances.2017015487. (PMID: 10.1182/bloodadvances.2017015487295351055851423) Politikos I, Lavery JA, Hilden P, Cho C, Borrill T, Maloy MA, Giralt SA, van den Brink MRM, Perales M, Barker JN (2020) Robust CD4 + T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin. Blood Adv 4:191–202. https://doi.org/10.1182/bloodadvances.2019000836. (PMID: 10.1182/bloodadvances.2019000836319352916960461) Barker JN, Devlin SM, Naputo KA et al (2020) High progression-free survival after intermediate intensity double unit cord blood transplantation in adults. Blood Adv 4:6064–6076. https://doi.org/10.1182/bloodadvances.2020003371. (PMID: 10.1182/bloodadvances.2020003371332905457724901) Brunstein CG, Weisdorf DJ, DeFor T, Barker JN, Tolar J, van Burik JH, Wagner JE (2006) Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood 108:2874–2880. https://doi.org/10.1182/blood-2006-03-011791. (PMID: 10.1182/blood-2006-03-011791168041131895580) Castillo N, García-Cadenas I, Barba P et al (2017) Early and long-term impaired T-Lymphocyte Immune reconstitution after cord blood transplantation with Antithymocyte Globulin. Biol Blood Marrow Transplant 23:491–497. https://doi.org/10.1016/j.bbmt.2016.11.014. (PMID: 10.1016/j.bbmt.2016.11.01427888015) Sanz J, Boluda J, Sanz MA et al (2012) Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen. Bone Marrow Transplantation (Basingstoke) 47:1287–1293. https://doi.org/10.1038/bmt.2012.13. (PMID: 10.1038/bmt.2012.13) Sanz J, Picardi A, Hernández Boluda JC et al (2013) Impact of graft-versus-host Disease Prophylaxis on outcomes after Myeloablative single-unit umbilical cord blood transplantation. Biol Blood Marrow Transplant 19:1387–1392. https://doi.org/10.1016/j.bbmt.2013.07.004. (PMID: 10.1016/j.bbmt.2013.07.00423850652) Sanz J, Wagner JE, Sanz MA, DeFor T, Montesinos P, Bachanova V, Lorenzo I, Warlick E, Sanz GF, Brunstein C (2013) Myeloablative Cord Blood Transplantation in adults with Acute Leukemia: comparison of two different transplant platforms. Biol Blood Marrow Transplant 19:1725–1730. https://doi.org/10.1016/j.bbmt.2013.09.015. (PMID: 10.1016/j.bbmt.2013.09.015240905984043182) Sanz GF, Saavedra S, Planelles D et al (2001) Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Blood 98:2332–2338. https://doi.org/10.1182/blood.V98.8.2332. (PMID: 10.1182/blood.V98.8.233211588027) Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18:295–304. https://doi.org/10.1097/00007890-197410000-00001. (PMID: 10.1097/00007890-197410000-000014153799) Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED (1995) 1994 Consensus Conference on Acute GVHD Grading. Bone marrow transplantation (Basingstoke) 15:825–828. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi M, Storb R, Donnall Thomas E (1980) Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 seattle patients. Am J Med 69:204–217. https://doi.org/10.1016/0002-9343(80)90380-0. (PMID: 10.1016/0002-9343(80)90380-06996481) Armand P, Kim HT, Logan BR et al (2014) Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood 123:3664–3671. https://doi.org/10.1182/blood-2014-01-552984. (PMID: 10.1182/blood-2014-01-552984247442694047501) Lucchini G, Perales M, Veys P (2015) Immune reconstitution after cord blood transplantation: peculiarities, clinical implications and management strategies. Cytotherapy (Oxford England) 17:711–722. https://doi.org/10.1016/j.jcyt.2015.03.614. (PMID: 10.1016/j.jcyt.2015.03.614) Komanduri KV, Wieder ED, Benjamin CL, Levy RB (2013) The evolving art of hematopoietic stem cell transplantation: translational research in post-transplant immune reconstitution and immunosuppression. Immunol Res 57:140–150. https://doi.org/10.1007/s12026-013-8461-4. (PMID: 10.1007/s12026-013-8461-424242818) Williams KM, Hakim FT, Gress RE (2007) T cell immune reconstitution following lymphodepletion. Semin Immunol 19:318–330. https://doi.org/10.1016/j.smim.2007.10.004. (PMID: 10.1016/j.smim.2007.10.004180233612180244) Szabolcs P, Niedzwiecki MD D (2007) Immune reconstitution after unrelated cord blood transplantation. Cytotherapy (Oxford England) 9:111–122. https://doi.org/10.1080/14653240701231014. (PMID: 10.1080/14653240701231014) Pascal L, Tucunduva L, Ruggeri A et al (2015) Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation. Blood 126:1027–1032. https://doi.org/10.1182/blood-2014-09-599241. (PMID: 10.1182/blood-2014-09-59924126160301) Politikos I, Boussiotis VA (2014) The role of the thymus in T-cell immune reconstitution after umbilical cord blood transplantation. Blood 124:3201–3211. https://doi.org/10.1182/blood-2014-07-589176. (PMID: 10.1182/blood-2014-07-589176252877084239330) Pukownik E, Kubicka M, Kurylo-Rafinska B et al (2018) Impact of CMV and EBV on Immune Recovery after allogeneic hematopoietic cell transplantation in children. Anticancer Res 38:6009–6013. https://doi.org/10.21873/anticanres.12950. (PMID: 10.21873/anticanres.1295030275233) Berger M, Figari O, Bruno B et al (2008) Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4 + cell count and transplant-related mortality. Bone Marrow Transplantation (Basingstoke) 41:55–62. https://doi.org/10.1038/sj.bmt.1705870. (PMID: 10.1038/sj.bmt.1705870) van der Maas NG, Berghuis D, van der Burg M, Lankester AC (2019) B cell reconstitution and influencing factors after hematopoietic stem cell transplantation in children. Front Immunol 10:782. https://doi.org/10.3389/fimmu.2019.00782. (PMID: 10.3389/fimmu.2019.00782310317696473193) |
| فهرسة مساهمة: | Keywords: Adults; Antithymocyte globulin; Cord blood transplant; Immune reconstitution |
| المشرفين على المادة: | 0 (Antilymphocyte Serum) D7RD81HE4W (thymoglobulin) 0 (Myeloablative Agonists) |
| تواريخ الأحداث: | Date Created: 20240418 Date Completed: 20240704 Latest Revision: 20240705 |
| رمز التحديث: | 20240705 |
| DOI: | 10.1007/s00277-024-05758-0 |
| PMID: | 38634914 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1432-0584 |
|---|---|
| DOI: | 10.1007/s00277-024-05758-0 |