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CD34+ Cell Enrichment

High incidence of graft failure in children receiving CD34+ augmented elutriated allografts for nonmalignant diseases

Bone Marrow Transplantation volume 31, pages 1073–1080 (2003)Cite this article

Summary:

T-cell depletion of the marrow graft using counterflow centrifugal elutriation reduces the risk of graft-versus-host disease (GVHD). However, because of high rates of graft failure and relapse, elutriation alone has not improved survival. We have carried out a phase II clinical trial in 54 pediatric patients to determine if CD34+ selection to rescue pluripotent stem cells from the small lymphocyte fraction improves engraftment. The processed grafts contained a mean of 5.5 × 107 cells/kg IBW, 4.7 × 106 CD34+ cells/kg IBW, and 6.3 × 105 CD3+cells/kg IBW. Patients achieved an ANC >500 at a median of 16 days and platelet count >20 000 at a median of 28 days. The incidence of clinically significant GVHD was 19%. In total, 10 patients enrolled in this study experienced graft failure, with eight of the 14 patients transplanted for nonmalignant indications failing to engraft stably. Graft failure was statistically significantly associated with nonmalignant diagnosis (P<0.001), but was not associated with CMV seropositivity, donor gender, or cell counts of the allograft. We conclude that although time to engraftment is similar to that seen with unmanipulated grafts, graft failure remains a significant problem in patients with hereditary, nonmalignant diseases. Future efforts will seek to preserve the benefits of elutriation with CD34+ selection by increasing immune ablation of the preparative regimen and/or increasing posttransplant immune suppression.

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References

  1. Rodt H, Kolb H, Netzel B et al. Effect of anti-T-cell globulin on GVHD in leukemic patients treated with BMT. Transplant Proc 1981; 13: 257–261.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Schapp N, Schattenberg A, Bar B et al. Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen. Br J Haematol 1997; 98: 750–759.

    Article  Google Scholar 

  4. Papadopoulos EB, Carabasi MH, Castro-Malaspina H et al. T-cell depleted allogeneic bone marrow transplantation as post remission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood 1998; 91: 1083–1089.

    CAS  PubMed  Google Scholar 

  5. Schattenberg A, Schaap N, Preijers F et al. Outcome of T-cell depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. Bone Marrow Transplant 2000; 26: 17–22.

    Article  CAS  Google Scholar 

  6. Noga S, Cremo C, Duff S et al. Large scale separation of human bone marrow by counterflow elutriation. J Immunol Methods 1986; 92: 211–218.

    Article  CAS  Google Scholar 

  7. Donnenberg A, Wagner J, Noga S et al. Lymphocyte depletion by counterflow centrifugal elutriation (CEE): analysis of engraftment. Exp Hematol 1989; 17: 541.

    Google Scholar 

  8. deWitte T, Hoogenhout J, de Pauw B et al. Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation. Blood 1986; 67: 1302–1308.

    CAS  Google Scholar 

  9. Wagner J, Santos G, Noga S et al. Bone marrow graft engineering by counterflow centrifugal elutriation: Results of a phase I–II clinical trial. Blood 1990; 75: 1370–1377.

    CAS  PubMed  Google Scholar 

  10. Schattenberg A, de Witte T, Preijers F et al. Allogeneic bone marrow transplantation for leukemia with marrow grafts depleted of lymphocytes by counterflow centrifugation. Blood 1990; 75: 1356–1363.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Klein JL, Avalos BR, Belt P et al. Bone marrow engraftment following unrelated donor transplantation utilizing busulfan and cyclophosphamide preparatory chemotherapy. Bone Marrow Transplant 1996; 17: 479–483.

    CAS  PubMed  Google Scholar 

  13. Jones R, Wagner J, Celano P et al. Separation of pluripotent haematopoietic stem cells from spleen colony-forming units. Nature 1990; 347: 188–189.

    Article  CAS  Google Scholar 

  14. Noga S, Davis J, Schepers K et al. The clinical use of elutriation and positive stem cell selection columns to engineer the lymphocyte and stem cell composition of the allograft. Prog Clin Biol Res 1994; 392: 317–324.

    Google Scholar 

  15. O'Donnell P, Jones R, Vogelsang G et al. CD34+ stem cell augmentation of elutriated allogeneic bone marrow grafts: results of a phase II clinical trial of engraftment and graft-versus-host disease prophylaxis in high-risk hematologic malignancies. Bone Marrow Transplant 1998; 22: 947–955.

    Article  CAS  Google Scholar 

  16. Noga S, Vogelsang G, Seber J et al. CD34+ Stem cell augmentation of allogeneic, elutriated marrow grafts improves engraftment but cyclosporine A is still required to reduce GVHD morbidity. Transplantat Proc 1997; 29: 728–732.

    Article  CAS  Google Scholar 

  17. Chao NJ, Schmidt GM, Niland JC et al. Cyclosporine, methotrexate, and prednisone compared to cyclosporine and prednisone for prophylaxis of acute graft-vs-host disease. N Engl J Med 1993; 329: 1225–1230.

    Article  CAS  Google Scholar 

  18. Gao I, Noga S, Wagner J et al. Implementation of a semi-closed large counterflow centrifugal elutriation system. J Clin Apheresis 1897; 3: 154–160.

    Article  Google Scholar 

  19. Kaplan EL, Meier P . Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  20. Greenwood M . The Errors of Sampling the Survivorship Tables [Appendix 1]. Reports on Public Health and Medical Subjects, 33. London, UK: Her Majesty's Stationery Office, 1926.

    Google Scholar 

  21. Vogelsang GB, Wagner JE . Graft-versus-host disease. Hematol Clin N Am 1990; 4: 625–638.

    Article  CAS  Google Scholar 

  22. Norwalk-Wegzyn A, King KE, Shirey RS . Fatal warm autoimmune hemolytic anemia resulting from IgM autoagglutinins in an infant with severe combined immunodeficiency. Am J Pediatr Hematol Oncol 2001; 23: 250–252.

    Article  Google Scholar 

  23. Kernan N, Bordignon C, Heller G et al. Graft failure after T-cell depleted human leukocyte antigen identical marrow transplants for leukemia: analysis of risk factors and results of secondary transplants. Blood 1989; 74: 2227–2236.

    CAS  PubMed  Google Scholar 

  24. 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 

  25. Elfenbein GJ, Mellits ED, Santos GW . Engraftment and survival after allogeneic bone marrow transplant for severe aplastic anemia. Bone Marrow Transplant 1983; 15: 1412–1416.

    Google Scholar 

  26. Guardiola PH, Pasquini R, Doka I et al. Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation. Blood 2000; 95: 422–429.

    CAS  PubMed  Google Scholar 

  27. Lucarelli G, Clift RA, Galimberti M et al. Marrow transplantation for patients with thalassemia. Results in class 3 patients. Blood 1996; 87: 2082–2088.

    CAS  PubMed  Google Scholar 

  28. Lucarelli G, Andreani M, Angelucci E . The cure of the thalassemia with bone marrow transplantation. Bone Marrow Transplant 2001; 28: 211–213.

    Article  Google Scholar 

  29. Baronciani D, Galimberti M, Lucarelli G et al. Bone marrow transplantation in class 1 thalassemia patients. Bone Marrow Transplant 1993; 12: S56–S58.

    Google Scholar 

  30. Giardini C, Galimberti M, Lucarelli G et al. Bone marrow transplantation in Class 2 thalassemia patients. Bone Marrow Transplant 1993; 12: S59–S62.

    Google Scholar 

  31. Hansen J, Gooley T, Martin P et al. Bone marrow transplantation from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med 1998; 338: 962–968.

    Article  CAS  Google Scholar 

  32. Donnenberg AD, Wagner JE, Noga SJ et al. Lymphocyte depletion by counterflow centrifugal elutriation (CCE): analysis of engraftment. Exp Hematol 1989; 17: 541.

    Google Scholar 

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  1. Departments of Oncology and Pediatrics, Johns Hopkins University, Baltimore, MD, USA

    C H McDonough, D A Jacobsohn, G B Vogelsang, S J Noga & A R Chen

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  1. C H McDonough
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  2. D A Jacobsohn
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  3. G B Vogelsang
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  4. S J Noga
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McDonough, C., Jacobsohn, D., Vogelsang, G. et al. High incidence of graft failure in children receiving CD34+ augmented elutriated allografts for nonmalignant diseases. Bone Marrow Transplant 31, 1073–1080 (2003). https://doi.org/10.1038/sj.bmt.1704071

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