Skip to main content
SpringerLink
Log in

Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts

  • Research Article
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo- SCT) and without showing any of the following events: poor graft function, grades II‒IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3+ Tcells, CD8+ T cells, and CD19+ B cells, and very slow in CD4+ T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune cells need not reach those in healthy donor in the first year after transplantation.We suggest that data from this recipient cohort should be used as reference values for post-transplant immune cell counts in patients receiving HSCT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bosch M, Khan FM, Storek J. Immune reconstitution after hematopoietic cell transplantation. Curr Opin Hematol 2012; 19 (4): 324–335

    Article  PubMed  Google Scholar 

  2. Lum LG. The kinetics of immune reconstitution after human marrow transplantation. Blood 1987; 69 (2): 369–380

    CAS  PubMed  Google Scholar 

  3. Chang YJ, Zhao XY, Huo MR, Xu LP, Liu DH, Liu KY, Huang XJ. Immune reconstitution following unmanipulated HLA-mismatched/haploidentical transplantation compared with HLA-identical sibling transplantation. J Clin Immunol 2012; 32 (2): 268–280

    Article  CAS  PubMed  Google Scholar 

  4. Bosch M, Dhadda M, Hoegh-Petersen M, Liu Y, Hagel LM, Podgorny P, Ugarte-Torres A, Khan FM, Luider J, Auer-Grzesiak I, Mansoor A, Russell JA, Daly A, Stewart DA, Maloney D, Boeckh M, Storek J. Immune reconstitution after anti-thymocyte globulinconditioned hematopoietic cell transplantation. Cytotherapy 2012; 14 (10): 1258–1275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Azevedo RI, Soares MVD, Albuquerque AS, Tendeiro R, Soares RS, Martins M, Ligeiro D, Victorino RMM, Lacerda JF, Sousa AE. Long-term immune reconstitution of naive and memory T cell pools after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19 (5): 703–712

    Article  CAS  PubMed  Google Scholar 

  6. Zhao XY, Chang YJ, Huang XJ. Conflicting impact of alloreactive NK cells on transplantation outcomes after haploidentical transplantation: do the reconstitution kinetics of natural killer cells create these differences? Biol Blood Marrow Transplant 2011; 17 (10): 1436–1442

    Article  PubMed  Google Scholar 

  7. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Zhang XH, Lu DP. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant 2009; 15 (2): 257–265

    Article  CAS  PubMed  Google Scholar 

  8. Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, Chen H, Han W, Chen YH, Wang FR, Wang JZ, Chen Y, Yan CH, Huo MR, Li D, Huang XJ. Who is the best donor for a related HLA haplotypemismatched transplant? Blood 2014; 124 (6): 843–850

    Article  CAS  PubMed  Google Scholar 

  9. Wang Y, Fu HX, Liu DH, Xu LP, Zhang XH, Chang YJ, Chen YH, Wang FR, Sun YQ, Tang FF, Liu KY, Huang XJ. Influence of two different doses of antithymocyte globulin in patients with standardrisk disease following haploidentical transplantation: a randomized trial. Bone Marrow Transplant 2014; 49 (3): 426–433

    Article  CAS  PubMed  Google Scholar 

  10. Kong Y, Chang YJ, Wang YZ, Chen YH, Han W, Wang Y, Sun YQ, Yan CH, Wang FR, Liu YR, Xu LP, Liu DH, Huang XJ. Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19 (10): 1465–1473

    Article  PubMed  Google Scholar 

  11. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15 (6): 825–828

    CAS  PubMed  Google Scholar 

  12. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11 (12): 945–956

    Article  Google Scholar 

  13. Servais S, Lengline E, Porcher R, Carmagnat M, Peffault de Latour R, Robin M, Sicre de Fontebrune F, Clave E, Maki G, Granier C, Xhaard A, Dhedin N, Molina JM, Toubert A, Moins-Teisserenc H, Socie G. Long-term immune reconstitution and infection burden after mismatched hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2014; 20 (4): 507–517

    Article  PubMed  Google Scholar 

  14. Robin M, Porcher R, De Castro Araujo R, de Latour RP, Devergie A, Rocha V, Larghero J, Adès L, Ribaud P, Mary JY, Socié G. Risk factors for late infections after allogeneic hematopoietic stem cell transplantation from a matched related donor. Biol Blood Marrow Transplant 2007; 13 (11): 1304–1312

    Article  PubMed  Google Scholar 

  15. Calandra T, Cohen J; International Sepsis Forum Definition of Infection in the ICU Consensus Conference. The international sepsis forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 2005; 33 (7): 1538–1548

    Article  PubMed  Google Scholar 

  16. Hoenigl M, Strenger V, Buzina W, Valentin T, Koidl C, Wölfler A, Seeber K, Valentin A, Strohmeier AT, Zollner-Schwetz I, Raggam RB, Urban C, Lass-Flörl C, Linkesch W, Krause R. European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) host factors and invasive fungal infections in patients with haematological malignancies. J Antimicrob Chemother 2012; 67 (8): 2029–2033

    Article  CAS  PubMed  Google Scholar 

  17. Storek J, Geddes M, Khan F, Huard B, Helg C, Chalandon Y, Passweg J, Roosnek E. Reconstitution of the immune system after hematopoietic stem cell transplantation in humans. Semin Immunopathol 2008; 30 (4): 425–437

    Article  PubMed  Google Scholar 

  18. De Cook LJ, Thoma M, Huneke T, Johnson ND, Wiegand RA, Patnaik MM, Litzow MR, Hogan WJ, Porrata LF, Holtan SG. Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning. Bone Marrow Transplant 2013; 48 (5): 708–714

    Article  Google Scholar 

  19. Chakrabarti S, Brown J, Guttridge M, Pamphilon DH, Lankester A, Marks DI. Early lymphocyte recovery is an important determinant of outcome following allogeneic transplantation with CD34+ selected graft and limited T-cell addback. Bone Marrow Transplant 2003; 32 (1): 23–30

    Article  CAS  PubMed  Google Scholar 

  20. Kim DH, Kim JG, Sohn SK, Sung WJ, Suh JS, Lee KS, Lee KB. Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation. Br J Haematol 2004; 125 (2): 217–224

    Article  PubMed  Google Scholar 

  21. Savani BN, Mielke S, Rezvani K, Montero A, Yong AS, Wish L, Superata J, Kurlander R, Singh A, Childs R, Barrett AJ. Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13 (10): 1216–1223

    Article  PubMed  PubMed Central  Google Scholar 

  22. Chang YJ, Zhao XY, Huo MR, Xu LP, Liu DH, Liu KY, Huang XJ. Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies. Am J Hematol 2011; 86 (2): 227–230

    Article  PubMed  Google Scholar 

  23. Powles R, Singhal S, Treleaven J, Kulkarni S, Horton C, Mehta J. Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation. Blood 1998; 91 (9): 3481–3486

    CAS  PubMed  Google Scholar 

  24. Bayraktar UD, Milton DR, Guindani M, Rondon G, Chen J, Al-Atrash G, Rezvani K, Champlin R, Ciurea SO. Optimal threshold and time of absolute lymphocyte count assessment for outcome prediction after bone marrow transplantation. Biol Blood Marrow Transplant 2016; 22 (3): 505–513

    Article  PubMed  Google Scholar 

  25. Kim HT, Armand P, Frederick D, Andler E, Cutler C, Koreth J, Alyea EP 3rd, Antin JH, Soiffer RJ, Ritz J, Ho VT. Absolute lymphocyte count recovery after allogeneic hematopoietic stem cell transplantation predicts clinical outcome. Biol Blood Marrow Transplant 2015; 21 (5): 873–880

    Article  PubMed  Google Scholar 

  26. Bühlmann L, Buser AS, Cantoni N, Gerull S, Tichelli A, Gratwohl A, Stern M. Lymphocyte subset recovery and outcome after T-cell replete allogeneic hematopoietic SCT. Bone Marrow Transplant 2011; 46 (10): 1357–1362

    Article  PubMed  Google Scholar 

  27. Storek J, Gooley T, Witherspoon RP, Sullivan KM, Storb R. Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts. Am J Hematol 1997; 54 (2): 131–138

    Article  CAS  PubMed  Google Scholar 

  28. Bartelink IH, Belitser SV, Knibbe CAJ, Danhof M, de Pagter AJ, Egberts TCG, Boelens JJ. Immune reconstitution kinetics as an early predictor for mortality using various hematopoietic stem cell sources in children. Biol Blood Marrow Transplant 2013; 19 (2): 305–313

    Article  PubMed  Google Scholar 

  29. Berger M, Figari O, Bruno B, Raiola A, Dominietto A, Fiorone M, Podesta M, Tedone E, Pozzi S, Fagioli F, Madon E, Bacigalupo A. Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant-related mortality. Bone Marrow Transplant 2008; 41 (1): 55–62

    Article  CAS  PubMed  Google Scholar 

  30. Kim DH, Sohn SK, Won DI, Lee NY, Suh JS, Lee KB. Rapid helper T-cell recovery above 200 × 106/L at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation. Bone Marrow Transplant 2006; 37 (12): 1119–1128

    Article  CAS  PubMed  Google Scholar 

  31. Koehl U, Bochennek K, Zimmermann SY, Lehrnbecher T, Sörensen J, Esser R, Andreas C, Kramm C, Grüttner HP, Falkenberg E, Orth A, Bader P, Schwabe D, Klingebiel T. Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+ CD3+ count reconstitution is associated with survival. Bone Marrow Transplant 2007; 39 (5): 269–278

    Article  CAS  PubMed  Google Scholar 

  32. Giannelli R, Bulleri M, Menconi M, Casazza G, Focosi D, Bernasconi S, Favre C. Reconstitution rate of absolute CD8+ T lymphocyte counts affects overall survival after pediatric allogeneic hematopoietic stem cell transplantation. J Pediatr Hematol Oncol 2012; 34 (1): 29–34

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the National High Technology Research and Development Program of China (863 Program; No. 2013AA020401) and the National Natural Science Foundation of China (No. 81470342).We thank the faculty members who collected the samples and analyzed the flow cytometric data.

Author information

Authors and Affiliations

  1. Peking University People’s Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China

    Xuying Pei, Xiangyu Zhao, Yu Wang, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Yingjun Chang & Xiaojun Huang

  2. Peking-Tsinghua Center for Life Sciences, Beijing, 100044, China

    Xiaojun Huang

Authors
  1. Xuying Pei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiangyu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lanping Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaohui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kaiyan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yingjun Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaojun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yingjun Chang or Xiaojun Huang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pei, X., Zhao, X., Wang, Y. et al. Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts. Front. Med. 12, 153–163 (2018). https://doi.org/10.1007/s11684-017-0548-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-017-0548-1

Keywords

Search

Navigation