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.

  • Original Article
  • Published:

Stem Cell Procurement

The impact of the age of HLA-identical siblings on mobilization and collection of PBSCs for allogeneic hematopoietic cell transplantation

Abstract

With the increasing age of patients undergoing allogeneic hematopoietic cell transplantation (HCT), the age of matched related sibling donors (MRDs) is expected to increase. Donor safety and the impact of donors’ age on mobilization, collection of peripheral hematopoietic progenitor cells (HPCs), subsequent engraftment and the incidence of GVHD were retrospectively analyzed. A total of 167 patients received HCT from an MRD. Median donors’ age was 48 years (67 (40%) donors were 50 years including 34 donors 60 years). Side effects under mobilization and apheresis were age independent. Grafts from donors <50 years contained more CD34+ cells (median 9 × 106/kg recipient's body weight (RBW)) compared with older donors (median 5.9 × 106/kg RBW) (P<0.0005), whereas harvests from donors 60 years contained more natural killer (NK) cells (P=0.003). Engraftment occurred at a median of 12 days after HCT irrespective of donors’ age. Increasing age of MRD did not preclude successful mobilization, collection of HPC and engraftment. In the context of more NK cells in grafts from elderly donors, the impact of donors’ age on outcome after HCT warrants further studies. Although short-term toxicities of apheresis were not increased with increasing age, long-term donor safety remains an important issue.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Gratwohl A, Baldomero H, Schwendener A, Rocha V, Apperley J, Frauendorfer K et al. The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies. Bone Marrow Transplant 2009; 43: 275–291.

    Article  CAS  PubMed  Google Scholar 

  2. Reddy RL . Mobilization and collection of peripheral blood progenitor cells for transplantation. Transfus Apher Sci 2005; 32: 63–72.

    Article  PubMed  Google Scholar 

  3. Hölig K, Kramer M, Kroschinsky F, Bornhäuser M, Mengling T, Schmidt AH et al. Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors. Blood 2009; 114: 3721–3722.

    Article  Google Scholar 

  4. Martino M, Console G, Dattola A, Callea I, Messina G, Moscato T et al. Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience. Bone Marrow Transplant 2009; 44: 163–168.

    Article  CAS  PubMed  Google Scholar 

  5. Halter J, Kodera Y, Ispizua AU, Greinix H, Schmitz H, Favre G et al. Severe events in donors after allogeneic hematopoietic stem cell donation. Haematologica 2009; 94: 94–101.

    Article  PubMed  Google Scholar 

  6. Champlin RE, Schmitz N, Horowitz MM, Chapuis B, Chopra R, Cornelissen JJ et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood 2000; 95: 3702–3709.

    CAS  PubMed  Google Scholar 

  7. Blaise D, Kuentz M, Fortanier C, Bourhis JH, Milpied N, Sutton L et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle. J Clin Oncol 2000; 18: 537–546.

    Article  CAS  PubMed  Google Scholar 

  8. Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–181.

    Article  CAS  PubMed  Google Scholar 

  9. Couban S, Barnett M . The source of cells for allografting. Biol Blood Marrow Transplant. 2003; 9: 669–673.

    Article  PubMed  Google Scholar 

  10. Gorin NC, Labopin M, Rocha V, Arcese W, Beksac M, Gluckman E et al. Marrow versus peripheral blood for geno-identical allogeneic stem cell transplantation in acute myelocytic leukemia: influence of dose and stem cell source shows better outcome with rich marrow. Blood 2003; 102: 3043–3051.

    Article  CAS  PubMed  Google Scholar 

  11. Gallardo D, de la Cámara R, Nieto JB, Espigado I, Iriondo A, Jiménez-Velasco A et al. Is mobilized peripheral blood comparable with bone marrow as a source of hematopoietic stem cells for allogeneic transplantation from HLA-identical sibling donors? A case-control study. Haematologica 2009; 94: 1282–1288.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Siddiq S, Pamphilon D, Brunskill S, Doree C, Hyde C, Stanworth S . Bone marrow harvest versus peripheral stem cell collection for haemopoietic stem cell donation in healthy donors. Cochrane Database Syst Rev 2009; 1: CD006406.

    Google Scholar 

  13. Gratwohl A, Baldomero H, Frauendorfer K, Rocha V, Apperley J, Niederwieser D . for the Joint Accreditation Committee of the International Society for Cellular Therapy ISCT and the European Group for Blood and Marrow Transplantation EBMT (JACIE). The EBMT activity survey 2006 on hematopoietic stem cell transplantation: focus on the use of cord blood products. Bone Marrow Transplant 2008; 41: 687–705.

    Article  CAS  PubMed  Google Scholar 

  14. Kreissig C, Kirsch A, Serke S . Characterization and measurement of CD34 expressing hematopoietic cells. J Chemother 1994; 3: 263–289.

    CAS  Google Scholar 

  15. Bryant E, Martin PJ . Documentation of engraftment and characterization of chimerism following hematopoietic cell transplantation. In: Thomas ED, Blume KG, Forman SJ (eds). Hematopoietic Cell Transplantation, 2nd edn. Blackwell Science: Boston, 1999, pp 197–206.

    Google Scholar 

  16. Tempescul A, Ianotto JC, Hardy E, Quivoron F, Petrov L, Berthou C . Peripheral blood stem cell collection in elderly patients. Ann Hematol. 2010; 89: 317–321.

    Article  PubMed  Google Scholar 

  17. Basara N, Schmetzer B, Blau IW, Bischoff M, Guenzelmann S, Kirsten D et al. Lenograstim-mobilized peripheral blood progenitor cells in volunteer donors: an open label randomized split dose escalating study. Bone Marrow Transplant 2000; 25: 371–376.

    Article  CAS  PubMed  Google Scholar 

  18. Inoue H, Yasuda Y, Hattori K, Shimizu T, Matsumoto M, Yabe M et al. The kinetics of immune reconstitution after cord blood transplantation and selected CD34_ stem cell transplantation in children: comparison with bone marrow transplantation. Int J Hematol. 2003; 77: 399–407.

    Article  PubMed  Google Scholar 

  19. Small TN, Avigan D, Dupont B, Smith K, Black P, Heller G et al. Immune reconstitution following T-cell depleted bone marrow transplantation: effect of age and posttransplant graft rejection prophylaxis. Biol Blood Marrow Transplant 1997; 3: 65–67.

    CAS  PubMed  Google Scholar 

  20. Small TN, Papadopoulos EB, Boulad F, Black P, Castro-Malaspina H, Childs BH et al. Comparison of immune reconstitution after unrelated and related T-cell depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood 1999; 93: 467–480.

    CAS  PubMed  Google Scholar 

  21. Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 1999; 94: 333–339.

    CAS  PubMed  Google Scholar 

  22. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.

    Article  CAS  PubMed  Google Scholar 

  23. Tanaka J, Tutumi Y, Mori A, Ohta S, Kobayashi S, Asaka M et al. Sequential analysis of HLA-C specific killer cell inhibitory receptor (CD158b) expressing peripheral blood mononuclear cells during chronic graft-versus-host disease. Bone Marrow Transplant 2000; 26: 287–90.

    Article  CAS  PubMed  Google Scholar 

  24. Tanaka J, Mori A, Ohta S, Yamamoto Y, Kobayashi S, Hashino S et al. Expression of HLA-C-specific natural killer cell receptors (CD158a and CD158b) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation. Br J Haematol 2000; 108: 778–783.

    Article  CAS  PubMed  Google Scholar 

  25. Bornhauser M, Thiede C, Brendel C, Geissler G, Oelschlaegel U, Neubauer A et al. Stable engraftment after megadose blood stem cell transplantation across the HLA barrier: the case for natural killer cells as graft-facilitating cells. Transplantation 1999; 68: 87–88.

    Article  CAS  PubMed  Google Scholar 

  26. Asai O, Longo DL, Tian ZG, Hornung RL, Taub DD, Ruscetti FW et al. Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation. J Clin Invest 1998; 101: 1835–1842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zeis M, Uharek L, Glass B, Gaska T, Steinmann J, Gassmann W et al. Allogeneic NK cells as potent anti-leukemic effector cells after allogeneic bone marrow transplantation in mice. Transplantation 1995; 59: 1734–1736.

    Article  CAS  PubMed  Google Scholar 

  28. Hauch M, Gazzola MV, Small T, Bordignon C, Barnett L, Cunningham I et al. Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia. Blood 1990; 7: 2250–2262.

    Google Scholar 

  29. Ruggeri L, Mancusi A, Capanni M, Urbani E, Carotti A, Aloisi T et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood 2007; 110: 433–440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hsu KC, Keever-Taylor KA, Wilton A, Pinto C, Heller G, Arkun K et al. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood 2005; 105: 4878–4884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Anderlini P, Champlin RE . Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges. Blood 2008; 111: 1767–1772.

    Article  CAS  PubMed  Google Scholar 

  32. Bennett CL, Evens AM, Andritsos LA, Balasubramanian L, Mai M, Fisher MJ et al. Haematological malignancies developing in previously healthy individuals who received haematopoietic growth factors: report from the Research on Adverse Drug Events and Reports (RADAR) project. Br J Haematol 2006; 135: 642–650.

    Article  CAS  PubMed  Google Scholar 

  33. Samson D, Slaper-Cortenbach I, Pamphilon D, McGrath E, McDonald F, Urbano Ispizua A . Current status of JACIE accreditation in Europe: a special report from the Joint Accreditation Committee of the ISCT and the EBMT (JACIE). Bone Marrow Transplant 2007; 39: 133–141.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H K Al-Ali.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Al-Ali, H., Bourgeois, M., Krahl, R. et al. The impact of the age of HLA-identical siblings on mobilization and collection of PBSCs for allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 46, 1296–1302 (2011). https://doi.org/10.1038/bmt.2010.310

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.310

Keywords

This article is cited by

Search

Quick links