Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Lymphocyte subset recovery following allogeneic bone marrow transplantation: CD4+-cell count and transplant-related mortality

Bone Marrow Transplantation volume 41, pages 19–21 (2008)Cite this article

T-cell recovery following SCT has been a research focus for clinical transplantation during recent years. Initial studies compared the cellular composition of mobilized PB stem cell products to BM stem cell products, and the effect of the utilized product on immune recovery following transplant. These studies reported both dramatic differences in the products,1, 2 as well as neutrophil and lymphocyte recovery post myeloablative transplantation.3 We have improved our understanding of the roles T cells and DCs have in GVHD and the differences in control of neoplastic disease following allogeneic SCT through these early studies. Subsequent research was focused on the relationship(s) between the frequency of T cells within stem cell products, rapidity of T-cell recovery post-SCT and clinical outcomes. These studies resulted in conflicting observations, including the finding of decreased GVHD following T-cell depletion,4, 5 as compared to positive correlations between the number of T cells within products, the rapidity of T-cell recovery6, 7 and improved clinical outcomes.6, 8, 9, 10, 11 Based on these results, current efforts to manipulate T-cell numbers and subsets within stem cell products have focused on the control of GVHD, immunologic recovery and clinical outcomes. The studies have also shown significant relationships between infused T-cell numbers, time to T-cell recovery and outcome parameters, including time to tumor progression, relapse-free survival and overall survival. In general, rapid T-cell recovery is associated with improved outcomes following allogeneic SCT.8, 9, 10, 11, 12, 13 Unfortunately, the majority of these allogeneic SCT studies have been with small patient numbers, typically incorporating a mixture of tumor types and conditioning regimes and resulting in varying conclusions. Thus, the identification of cellular effectors in the stem cell products has varied, including their relationships between clinical outcomes and recovery of CD3+, CD4+, CD8+ or natural killer (NK) cells.

In this issue of Bone Marrow Transplantation, Berger et al.14 report that rapid recovery of CD4+ T lymphocytes results in a significant decrease in transplant-related mortality (TRM) based on a cohort of 758 BM allograft patients. This report is consistent with an earlier study by Kim et al.,8 which reported that rapid CD4+ T-cell recovery to greater than 2 × 108 cells/l at 3 months in 69 allogeneic SCT recipients was associated with a significantly better clinical outcome. This included correlations with overall survival, non-relapse mortality and opportunistic infections. The 69 recipients included patients with ALL and CML, whose peripheral lymphocytic subsets of CD3+ T cells, CD4+ T helper cells and CD8+ cytotoxic T cells, as well as CD56+ NK cells, were measured at 3, 6 and 12 months post transplant. Further, it was reported that the frequency of infused CD4+ cells correlated with a more rapid CD4+-cell recovery. In addition, significantly better overall survival and non-relapse mortality rates and a decrease in opportunistic infections were observed in patients with rapid CD4 T-cell recovery, but not rapid CD3-, CD8- or NK-cell recovery. The observation of a correlation between CD4+-cell number infused and rapidity of CD4+-cell number recovery post transplant is consistent with other prior studies that reported a positive association between CD4+-cell counts in stem cell products and CD4+-cell recovery.6, 7 Storek et al.13 also reported that rapid CD4+-cell recovery was associated with a decreased risk of infections. In contrast to the correlations with CD4+ cells, a study by Koehl et al.9 examined 32 pediatric patients undergoing allogeneic SCT at 4, 9, 20 and 28 weeks following SCT and reported improved survival in patients whose absolute CD8+ T-lymphocyte counts were above the 5th percentile of age-matched control levels during the first year of post-SCT as compared to patients who never achieved this level post-SCT. Further, no correlations were observed with total T cells or CD4+ cells. Similar results regarding clinical outcomes were obtained in studies of CD8+ cell numbers at 6 months in 42 adult allotransplant patients.10 A potential role for NK cells in improving clinical outcomes was also reported by Savani et al.12 in a study using a cohort of 54 myeloid leukemia patients. They reported that those patients who had NK cellularity greater than 150/μl at 30 days post transplant had significantly lower relapse rates, acute GVHD (aGVHD) rates and non-relapse mortality rates, as well as improved survival. This report was confirmed and built on their prior study of 20 CML patients whose NK reconstitution was associated with molecular remission.15

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Mills KC, Gross TG, Varney ML, Heimann DG, Reed EC, Kessinger A et al. Immunologic phenotype and function in human bone marrow, blood stem cells and umbilical cord blood. Bone Marrow Transplant 1996; 18: 53–61.

    CAS  PubMed  Google Scholar 

  2. Pavletic ZS, Bishop MR, Tarantolo SR, Martin-Algarra S, Bierman PJ, Vose JM et al. Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies. J Clin Oncol 1997; 15: 1608–1616.

    Article  CAS  PubMed  Google Scholar 

  3. Tayebi H, Tiberghien P, Ferrand C, Lienard A, Duperrier A, Cahn JY et al. Allogeneic peripheral blood stem cell transplantation results in less alteration of early T cell compartment homeostasis than bone marrow transplantation. Bone Marrow Transplant 2001; 27: 167–175.

    Article  CAS  PubMed  Google Scholar 

  4. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    Article  CAS  PubMed  Google Scholar 

  5. Chakrabarti S, MacDonald D, Hale G, Holder K, Turner V, Czarnecka H et al. T-cell depletion with Campath-1H ‘in the bag’ for matched related allogeneic peripheral blood stem cell transplantation is associated with reduced graft-versus-host disease, rapid immune constitution and improved survival. Br J Haematol 2003; 121: 109–118.

    Article  PubMed  Google Scholar 

  6. Menendez P, Perez-Simon JA, Mateos MV, Caballero MD, Gonzalez M, San-Miguel JF et al. Influence of the different CD34+ and CD34- cell subsets infused on clinical outcome after non-myeloablative allogeneic peripheral blood transplantation from human leucocyte antigen-identical sibling donors. Br J Haematol 2002; 119: 135–143.

    Article  PubMed  Google Scholar 

  7. Storek J, Dawson MA, Maloney DG . Correlation between the numbers of naive T cells infused with blood stem cell allografts and the counts of naive T cells after transplantation. Biol Blood Marrow Transplant 2003; 9: 781–784.

    Article  PubMed  Google Scholar 

  8. Kim DH, Sohn SK, Won DI, Lee NY, Suh JS, Lee KB . Rapid helper T-cell recovery above 200 × 10 6/l at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation. Bone Marrow Transplant 2006; 37: 1119–1128.

    Article  CAS  PubMed  Google Scholar 

  9. Koehl U, Bochennek K, Zimmermann SY, Lehrnbecher T, Sorensen J, Esser R et al. Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+ CD3+ count reconstitution is associated with survival. Bone Marrow Transplant 2007; 39: 269–278.

    Article  CAS  PubMed  Google Scholar 

  10. Novitzky N, Davison GM, Hale G, Waldmann H . Immune reconstitution at 6 months following T-cell depleted hematopoietic stem cell transplantation is predictive for treatment outcome. Transplantation 2002; 74: 1551–1559.

    Article  CAS  PubMed  Google Scholar 

  11. 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: 23–30.

    Article  CAS  PubMed  Google Scholar 

  12. Savani BN, Mielke S, Adams S, Uribe M, Rezvani K, Yong AS et al. Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia. Leukemia 2007 (E-pub ahead of print).

  13. 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: 131–138.

    Article  CAS  PubMed  Google Scholar 

  14. Berger M, Figari O, Bruno B, Raiola A, Dominietto A, Fiorone M et al. Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant related mortality. Bone Marrow Transplant 2007 (in press).

  15. Savani BN, Rezvani K, Mielke S, Montero A, Kurlander R, Carter CS et al. Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2006; 107: 1688–1695.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Storek J, Witherspoon RP, Storb R . T cell reconstitution after bone marrow transplantation into adult patients does not resemble T cell development in early life. Bone Marrow Transplant 1995; 16: 413–425.

    CAS  PubMed  Google Scholar 

  17. Atkinson K, Hansen JA, Storb R, Goehle S, Goldstein G, Thomas ED . T-cell subpopulations identified by monoclonal antibodies after human marrow transplantation. I. Helper-inducer and cytotoxic-suppressor subsets. Blood 1982; 59: 1292–1298.

    CAS  PubMed  Google Scholar 

  18. Heining C, Spyridonidis A, Bernhardt E, Schulte-Monting J, Behringer D, Grullich C et al. Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients. Bone Marrow Transplant 2007; 39: 613–622.

    Article  CAS  PubMed  Google Scholar 

  19. Talmadge JE . Pathways mediating the expansion and immunosuppressive activity of MDSCs, and their relevance to cancer therapy. Clin Cancer Res 2007 (E-pub ahead of print).

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

    J E Talmadge

Authors
  1. J E Talmadge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J E Talmadge.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Talmadge, J. Lymphocyte subset recovery following allogeneic bone marrow transplantation: CD4+-cell count and transplant-related mortality. Bone Marrow Transplant 41, 19–21 (2008). https://doi.org/10.1038/sj.bmt.1705871

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705871

This article is cited by

Search

Advanced search

Quick links