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:

CD34+ Cell Transplants

Transplantation of highly purified peripheral-blood CD34+ progenitor cells from related and unrelated donors in children with nonmalignant diseases

Summary:

Transplantation of allogeneic stem cells is currently the only curative treatment for some nonmalignant pediatric diseases. We investigated whether transplantation of purified CD34+ stem cells prevents acute and chronic GvHD and reduces transplant-related mortality. A total of 25 pediatric patients with nonmalignant diseases underwent allogeneic transplantation from 26 donors (matched related n=4, matched or partially matched unrelated n=14, mismatched related n=8). All grafts were purified peripheral-blood CD34+ stem cells mobilized with G-CSF. Patients received a median of 12.9 × 106 CD34+ progenitor cells with a median of 6.1 × 103 contaminating T-lymphocytes per kilogram of body weight. No post transplant immunosuppressive drugs were given for prophylaxis of GvHD. Engraftment was seen in 21 patients. Three patients engrafted after a second transplant and one patient failed to engraft. Two patients had autologous reconstitution 1.5 years post transplant and one of them was successfully retransplanted. No acute GvHD >grade II was seen, and only two patients developed limited, chronic GvHD. In all, 22 patients (88%) are alive with a median follow-up of 3.7 years. In total, 19 patients (76%) are free of disease or of progression. Transplantation of highly purified peripheral-blood CD34+ stem cells is associated with low toxicity in patients with nonmalignant diseases.

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. Horwitz MM . Uses and growth of hematopoietic cell transplantation. In: Thomas ED, Blume KG, Forman SJ (eds). Hematopoietic Cell Transplantation. Malden, MA: Oxford University Press, 1998, pp 12–18.

    Google Scholar 

  2. Dominietto A, Lamparelli T, Raiola AM et al. Transplant-related mortality and long-term graft function are significantly influenced by cell dose in patients undergoing allogeneic marrow transplantation. Blood 2002; 100: 3930–3934.

    Article  CAS  PubMed  Google Scholar 

  3. Storb R, Prentice RL, Thomas ED . Marrow transplantation for treatment of aplastic anemia. An analysis of factors associated with graft rejection. N Engl J Med 1977; 296: 61–66.

    Article  CAS  PubMed  Google Scholar 

  4. Martino R, Subira M, Rovira M et al. Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients. Br J Haematol 2002; 116: 475–482.

    Article  PubMed  Google Scholar 

  5. Ljungman P . Prevention and treatment of viral infections in stem cell transplant recipients. Br J Haematol 2002; 118: 44–57.

    Article  CAS  PubMed  Google Scholar 

  6. Ferrara JL, Deeg HJ . Graft-vs-host disease. N Engl J Med 1991; 324: 667–674.

    Article  CAS  PubMed  Google Scholar 

  7. Beatty PG, Hansen JA, Longton GM et al. Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies. Transplantation 1991; 51: 443–447.

    Article  CAS  PubMed  Google Scholar 

  8. Beatty PG, Clift RA, Mickelson EM et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985; 313: 765–771.

    Article  CAS  PubMed  Google Scholar 

  9. Anasetti C, Hansen JA . Effect of HLA incompatibility in marrow transplantation from unrelated and HLA-mismatched related donors. Transfus Sci 1994; 15: 221–230.

    Article  CAS  PubMed  Google Scholar 

  10. Anasetti C, Hansen J . Bone marrow transplantation from HLA-partially matched related donors and unrelated volunteer donors. In: Forman SJ, Blume KG, Thomas ED (eds) Bone Marrow Transplantation. Cambridge, MA: Blackwell Scientific Publications, 1993, pp 665–679.

    Google Scholar 

  11. Lee SJ, Klein JP, Barrett AJ et al. Severity of chronic graft-vs-host disease: association with treatment-related mortality and relapse. Blood 2002; 100: 406–414.

    Article  CAS  PubMed  Google Scholar 

  12. Lee SJ, Zahrieh D, Alyea EP et al. Comparison of T-cell-depleted and non-T-cell-depleted unrelated donor transplantation for hematologic diseases: clinical outcomes, quality of life, and costs. Blood 2002; 100: 2697–2702.

    Article  CAS  PubMed  Google Scholar 

  13. Goerner M, Gooley T, Flowers ME et al. Morbidity and mortality of chronic GVHD after hematopoietic stem cell transplantation from HLA-identical siblings for patients with aplastic or refractory anemias. Biol Blood Marrow Transplant 2002; 8: 47–56.

    Article  CAS  PubMed  Google Scholar 

  14. Ho VT, Soiffer RJ . The history and future of T-cell depletion as graft-vs-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 2001; 98: 3192–3204.

    Article  CAS  PubMed  Google Scholar 

  15. Urbano-Ispizua A, Rozman C, Pimentel P et al. The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings. Blood 2001; 97: 383–387.

    Article  CAS  PubMed  Google Scholar 

  16. Reisner Y, Martelli MF . Tolerance induction by ‘megadose’ transplants of CD34+ stem cells: a new option for leukemia patients without an HLA-matched donor. Curr Opin Immunol 2000; 12: 536–541.

    Article  CAS  PubMed  Google Scholar 

  17. Blau IW, Basara N, Lentini G et al. Feasibility and safety of peripheral blood stem cell transplantation from unrelated donors: results of a single-center study. Bone Marrow Transplant 2001; 27: 27–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Handgretinger R, Lang P, Schumm M et al. Immunological aspects of haploidentical stem cell transplantation in children. Ann NY Acad Sci 2001; 938: 340–357.

    Article  CAS  PubMed  Google Scholar 

  19. Lang P, Handgretinger R, Niethammer D et al. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood 2003; 101: 1630–1636.

    Article  CAS  PubMed  Google Scholar 

  20. Aversa F, Tabilio A, Velardi A 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 

  21. Handgretinger R, Schumm M, Lang P et al. Transplantation of megadoses of purified haploidentical stem cells. Ann NY Acad Sci 1999; 872: 351.

    Article  CAS  PubMed  Google Scholar 

  22. Handgretinger R, Klingebiel T, Lang P et al. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant 2001; 27: 777–783.

    Article  CAS  PubMed  Google Scholar 

  23. Henter JI, Arico M, Egeler RM et al. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH Study Group of the Histiocyte Society. Med Pediatr Oncol 1997; 28: 342–347.

    Article  CAS  PubMed  Google Scholar 

  24. Lucarelli G, Galimberti M, Polchi P et al. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med 1993; 329: 840–844.

    Article  CAS  PubMed  Google Scholar 

  25. Lang P, Schumm M, Taylor G et al. Clinical scale isolation of highly purified peripheral CD34+ progenitors for autologous and allogeneic transplantation in children. Bone Marrow Transplant 1999; 24: 583–589.

    Article  CAS  PubMed  Google Scholar 

  26. Schumm M, Lang P, Taylor G et al. Isolation of highly purified autologous and allogeneic peripheral CD34+ cells using the CliniMACS device. J Hematother 1999; 8: 209–218.

    Article  CAS  PubMed  Google Scholar 

  27. Rowlings PA, Przepiorka D, Klein JP et al. IBMTR Severity Index for grading acute graft-vs-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997; 97: 855–864.

    Article  CAS  PubMed  Google Scholar 

  28. Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Stat Assoc 2003; 53: 457–481.

    Article  Google Scholar 

  29. Schlegel PG, Eyrich M, Bader P et al. OKT-3-based reconditioning regimen for early graft failure in HLA-non-identical stem cell transplants. Br J Haematol 2000; 111: 668–673.

    Article  CAS  PubMed  Google Scholar 

  30. Nash RA, Pepe MS, Storb R et al. Acute graft-vs-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 1992; 80: 1838–1845.

    CAS  PubMed  Google Scholar 

  31. Horowitz MM, Gale RP, Sondel PM et al. Graft-vs-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  32. Atkinson K, Horowitz MM, Gale RP et al. Risk factors for chronic graft-vs-host disease after HLA-identical sibling bone marrow transplantation. Blood 1990; 75: 2459–2464.

    CAS  PubMed  Google Scholar 

  33. Martin PJ, Hansen JA, Torok-Storb B et al. Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants. Bone Marrow Transplant 1988; 3: 445–456.

    CAS  PubMed  Google Scholar 

  34. Marmont AM, Horowitz MM, Gale RP et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991; 78: 2120–2130.

    CAS  PubMed  Google Scholar 

  35. Powles RL, Morgenstern GR, Kay HE et al. Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. Lancet 1983; 1: 612–615.

    Article  CAS  PubMed  Google Scholar 

  36. Eyrich M, Lang P, Lal S et al. A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigen-disparate haematopoietic stem cells from parental donors. Br J Haematol 2001; 114: 422–432.

    Article  CAS  PubMed  Google Scholar 

  37. Andreani M, Nesci S, Lucarelli G et al. Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation. Bone Marrow Transplant 2000; 25: 401–404.

    Article  CAS  PubMed  Google Scholar 

  38. Haines SJ, Erickson DL, Wirtschafter JD . Optic nerve decompression for osteopetrosis in early childhood. Neurosurgery 1988; 23: 470–475.

    Article  CAS  PubMed  Google Scholar 

  39. Horwitz EM, Prockop DJ, Fitzpatrick LA et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5: 309–313.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ruben Siedner, Christine Faleyras, Annie Babarin-Dorner, Olga Bartuli, Christiane Braun, Gabi Hochwelker, and Ulrike Krauter for excellent technical assistance and Sharon Naron for excellent editorial assistance. We thank Dr Paul Woodard for critical reading of the manuscript and helpful suggestions. We thank all the volunteers who donated mobilized peripheral stem cells, especially those who were willing to donate a second time if necessary. This work was supported by a grant from the Jose Carreras Foundation (DJCLS-R3) and from the Deutsche Forschungsgemeinschaft (SFB 510).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R Handgretinger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lang, P., Klingebiel, T., Bader, P. et al. Transplantation of highly purified peripheral-blood CD34+ progenitor cells from related and unrelated donors in children with nonmalignant diseases. Bone Marrow Transplant 33, 25–32 (2004). https://doi.org/10.1038/sj.bmt.1704303

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704303

Keywords

This article is cited by

Search

Quick links