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Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning

Leukemia volume 20, pages 1690–1700 (2006)Cite this article

Abstract

Allogeneic hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning has been extensively evaluated in patients with hematologic malignancies who are ineligible for conventional HCT because of age or medical comorbidities. Nonmyeloablative regimens have led to an initial state of mixed hematopoietic chimerism defined as coexistence of donor- and host-derived hematopoiesis. While nonmyeloablative regimens have been associated with reduced regimen-related toxicities in comparison with conventional myeloablative conditioning, graft rejection, graft-versus-host disease (GVHD), and disease progression have remained significant challenges. In this article, after briefly introducing current techniques for chimerism assessment, we describe factors affecting donor chimerism levels after nonmyeloablative conditioning, and then review data suggesting that chimerism assessment early after HCT might help identify patients at risk for graft rejection, GVHD and relapse/progression. Finally, we discuss how these observations have opened the way to further research protocols evaluating manipulation of postgrafting immunosuppression, and/or infusion of donor immune cells.

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References

  1. Bader P, Niethammer D, Willasch A, Kreyenberg H, Klingebiel T . How and when should we monitor chimerism after allogeneic stem cell transplantation? (Review). Bone Marrow Transplant 2005; 35: 107–119.

    Article  CAS  PubMed  Google Scholar 

  2. Antin JH, Childs R, Filipovich AH, Giralt S, Mackinnon S, Spitzer T et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings (Review). Biol Blood Marrow Transplant 2001; 7: 473–485.

    Article  CAS  PubMed  Google Scholar 

  3. Santos GW, Sensenbrenner LL, Burke PJ, Colvin M, Owens Jr AH, Bias WB et al. Marrow transplantation in man following cyclophosphamide. Transplant Proc 1971; 3: 400–404.

    CAS  PubMed  Google Scholar 

  4. Hill RS, Petersen FB, Storb R, Appelbaum FR, Doney K, Dahlberg S et al. Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with a higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease. Blood 1986; 67: 811–816.

    CAS  PubMed  Google Scholar 

  5. Huss R, Deeg HJ, Gooley T, Bryant E, Leisenring W, Clift R et al. Effect of mixed chimerism on graft-versus-host disease, disease recurrence, and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia. Bone Marrow Transplant 1996; 18: 767–776.

    CAS  PubMed  Google Scholar 

  6. Branch DR, Gallagher MT, Forman SJ, Winkler KJ, Petz LD, Blume KG . Endogenous stem cell repopulation resulting in mixed hematopoietic chimerism following total body irradiation and marrow transplantation for acute leukemia. Transplantation 1982; 34: 226–228.

    Article  CAS  PubMed  Google Scholar 

  7. Bertheas MF, Lafage M, Levy P, Blaise D, Stoppa AM, Viens P et al. Influence of mixed chimerism on the results of allogeneic bone marrow transplantation for leukemia. Blood 1991; 78: 3103–3106.

    CAS  PubMed  Google Scholar 

  8. Petz LD . Documentation of engraftment and characterization of chimerism following bone marrow transplantation. In: Forman SJ, Blume KG, Thomas ED (eds). Bone Marrow Transplantation. Blackwell Scientific Publications: Boston, MA, 1994, pp 136–148.

    Google Scholar 

  9. Bretagne S, Vidaud M, Kuentz M, Cordonnier C, Henni T, Vinci G et al. Mixed blood chimerism in T cell-depleted bone marrow transplant recipients: Evaluation using DNA polymorphisms. Blood 1987; 70: 1692–1695.

    CAS  PubMed  Google Scholar 

  10. Roy DC, Tantravahi R, Murray C, Dear K, Gorgone B, Anderson KC et al. Natural history of mixed chimerism after bone marrow transplantation with CD6-depleted allogeneic marrow: a stable equilibrium. Blood 1990; 75: 296–304.

    CAS  PubMed  Google Scholar 

  11. Schaap N, Schattenberg A, Mensink E, Preijers F, Hillegers M, Knops R et al. Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation. Leukemia 2002; 16: 13–21.

    Article  CAS  PubMed  Google Scholar 

  12. Mackinnon S, Barnett L, Heller G, O'Reilly RJ . Minimal residual disease is more common in patients who have mixed T-cell chimerism after bone marrow transplantation for chronic myelogenous leukemia. Blood 1994; 83: 3409–3416.

    CAS  PubMed  Google Scholar 

  13. Baron F, Sandmaier BM . Current status of hematopoietic stem cell transplantation after nonmyeloablative conditioning. Curr Opin Hematol 2005; 12: 435–443.

    Article  PubMed  Google Scholar 

  14. Baron F, Storb R . Allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning as treatment for hematologic malignancies and inherited blood disorders (Review). Mol Ther 2006; 13: 26–41.

    Article  CAS  PubMed  Google Scholar 

  15. Childs RW, Barrett J . Nonmyeloablative allogeneic immunotherapy for solid tumors (Review). Annu Rev Med 2004; 55: 459–475.

    Article  CAS  PubMed  Google Scholar 

  16. Giralt S, Estey E, Albitar M, van Besien K, Rondón G, Anderlini P et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  17. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  18. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  PubMed  Google Scholar 

  19. Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005; 23: 1993–2003.

    Article  PubMed  Google Scholar 

  20. Mohty M, de Lavallade H, Ladaique P, Faucher C, Vey N, Coso D et al. The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison. Leukemia 2005; 19: 916–920.

    Article  CAS  PubMed  Google Scholar 

  21. Shimoni A, Kröger N, Zabelina T, Ayuk F, Hardan I, Yeshurun M et al. Hematopoietic stem-cell transplantation from unrelated donors in elderly patients (age >55 years) with hematologic malignancies: older age is no longer a contraindication when using reduced intensity conditioning. Leukemia 2005; 19: 7–12.

    Article  CAS  PubMed  Google Scholar 

  22. Burroughs L, Storb R . Low-intensity allogeneic hematopoietic stem cell transplantation for myeloid malignancies: separating graft-versus-leukemia effects from graft-versus-host disease. Curr Opin Hematol 2005; 12: 45–54.

    Article  PubMed  Google Scholar 

  23. Champlin R, Khouri I, Shimoni A, Gajewski J, Kornblau S, Molldrem J et al. Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy. Br J Haematol 2000; 111: 18–29.

    Article  CAS  PubMed  Google Scholar 

  24. Storb RF, Champlin R, Riddell SR, Murata M, Bryant S, Warren EH . Non-myeloablative transplants for malignant disease. In: Schechter GP, Broudy VC, Williams ME (eds). Hematology 2001: American Society of Hematology Education Program Book. The American Society of Hematology: Washington, DC, 2001, pp 375–391.

    Google Scholar 

  25. Appelbaum FR . Dose intensity and the toxicity and efficacy of allogeneic hematopoietic cell transplantation (Keynote Address). Leukemia 2005; 19: 171–175.

    Article  CAS  PubMed  Google Scholar 

  26. de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 865–872.

    Article  CAS  PubMed  Google Scholar 

  27. Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.

    CAS  PubMed  Google Scholar 

  28. Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N et al. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2003; 9: 320–329.

    Article  PubMed  Google Scholar 

  29. Carvallo C, Geller N, Kurlander R, Srinivasan R, Mena O, Igarashi T et al. Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors. Blood 2004; 103: 1560–1563.

    Article  CAS  PubMed  Google Scholar 

  30. Baron F, Baker JE, Storb R, Gooley TA, Sandmaier BM, Maris MB et al. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004; 104: 2254–2262.

    Article  CAS  PubMed  Google Scholar 

  31. Ueno NT, Cheng YC, Rondon G, Tannir NM, Gajewski JL, Couriel DR et al. Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors. Blood 2003; 102: 3829–3836.

    Article  CAS  PubMed  Google Scholar 

  32. Bryant E, Martin PJ . Documentation of engraftment and characterization of chimerism following hematopoietic cell transplantation. In: Blume KG, Forman SJ, Appelbaum FR (eds). Thomas' Hematopoietic Cell Transplantation. Blackwell Publishing Ltd.: Oxford, UK, 2004, pp 234–243.

    Google Scholar 

  33. Thiede C . Diagnostic chimerism analysis after allogeneic stem cell transplantation: new methods and markers (Review). Am J PharmacoGenom 2004; 4: 177–187.

    Article  CAS  Google Scholar 

  34. Hochberg EP, Ritz J . Hematpoietic chimerism after allogeneic stem cell transplantation. In: Atkinson K, Champlin R, Ritz J, Fibbe WE, Ljungman P, Brenner MK (eds). Clinical Bone Marrow and Blood Stem Cell Transplantation. Cambridge University Press: Cambridge, UK, 2004, pp 466–478.

    Google Scholar 

  35. Durnam DM, Anders KR, Fisher L, O'Quigley JO, Bryant EM, Thomas ED . Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay. Blood 1989; 74: 2220–2226.

    CAS  PubMed  Google Scholar 

  36. Mackinnon S, Barnett L, Bourhis JH, Black P, Heller G, O'Reilly RJ . Myeloid and lymphoid chimerism after T-cell-depleted marrow transplantation: evaluation of conditioning regimens using the polymerase chain reaction to amplify human minisatellite regions of genomic DNA. Blood 1992; 80: 3235–3241.

    CAS  PubMed  Google Scholar 

  37. Thiede C, Bornhauser M, Ehninger G . Evaluation of STR informativity for chimerism testing – comparative analysis of 27 STR systems in 203 matched related donor recipient pairs. Leukemia 2004; 18: 248–254.

    Article  CAS  PubMed  Google Scholar 

  38. Thiede C, Florek M, Bornhäuser M, Ritter M, Mohr B, Brendel C et al. Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection. Bone Marrow Transplant 1999; 23: 1055–1060.

    Article  CAS  PubMed  Google Scholar 

  39. Scharf SJ, Smith AG, Hansen JA, McFarland C, Erlich HA . Quantitative determination of bone marrow transplant engraftment using fluorescent polymerase chain reaction primers for human identity markers. Blood 1995; 85: 1954–1963.

    CAS  PubMed  Google Scholar 

  40. Schichman SA, Suess P, Vertino AM, Gray PS . Comparison of short tandem repeat and variable number tandem repeat genetic markers for quantitative determination of allogeneic bone marrow transplant engraftment. Bone Marrow Transplant 2002; 29: 243–248.

    Article  CAS  PubMed  Google Scholar 

  41. Hancock JP, Goulden NJ, Oakhill A, Steward CG . Quantitative analysis of chimerism after allogeneic bone marrow transplantation using immunomagnetic selection and fluorescent microsatellite PCR (Review). Leukemia 2003; 17: 247–251.

    Article  CAS  PubMed  Google Scholar 

  42. Kroger N, Zagrivnaja M, Schwartz S, Badbaran A, Zabelina T, Lioznov M et al. Kinetics of plasma-cell chimerism after allogeneic stem cell transplantation by highly sensitive real-time PCR based on sequence polymorphism and its value to quantify minimal residual disease in patients with multiple myeloma. Exp Hematol 2006; 34: 688–694.

    Article  CAS  PubMed  Google Scholar 

  43. McSweeney PA, Storb R . Mixed chimerism: preclinical studies and clinical applications (Review). Biol Blood Marrow Transplant 1999; 5: 192–203.

    Article  CAS  PubMed  Google Scholar 

  44. Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C et al. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood 2002; 99: 4618–4625.

    Article  CAS  PubMed  Google Scholar 

  45. Fredriksson M, Barbany G, Liljedahl U, Hermanson M, Kataja M, Syvanen AC . Assessing hematopoietic chimerism after allogeneic stem cell transplantation by multiplexed SNP genotyping using microarrays and quantitative analysis of SNP alleles. Leukemia 2004; 18: 255–266.

    Article  CAS  PubMed  Google Scholar 

  46. Masmas TN, Madsen HO, Petersen SL, Ryder LP, Svejgaard A, Alizadeh M et al. Evaluation and automation of hematopoietic chimerism analysis based on real-time quantitative polymerase chain reaction. Biol Blood Marrow Transplant 2005; 11: 558–566.

    Article  CAS  PubMed  Google Scholar 

  47. Hogan WJ, Little M-T, Zellmer E, Friedetzky A, Diaconescu R, Gisburne S et al. Postgrafting immunosuppression with sirolimus and cyclosporine facilitates stable mixed hematopoietic chimerism in dogs given sublethal total body irradiation before marrow transplantation from DLA-identical littermates. Biol Blood Marrow Transplant 2003; 9: 489–495.

    Article  CAS  PubMed  Google Scholar 

  48. Kahl C, Mielcarek M, Iwata M, Harkey MA, Storer B, Torok-Storb B . Radiation dose determines the degree of myeloid engraftment following nonmyeloablative stem cell transplantation. Biol Blood Marrow Transplant 2004; 10: 826–833.

    Article  PubMed  Google Scholar 

  49. Panse JP, Heimfeld S, Guthrie KA, Maris MB, Maloney DG, Baril BB et al. Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after nonmyeloablative conditioning. Br J Haematol 2005; 128: 659–667.

    Article  CAS  PubMed  Google Scholar 

  50. Tykodi SS, Warren EH, Thompson JA, Riddell SR, Childs RW, Otterud BE et al. Allogeneic hematopoietic cell transplantation for metastatic renal cell carcinoma after nonmyeloablative conditioning: toxicity, clinical response, and immunological response to minor histocompatibility antigens. Clin Cancer Res 2004; 10: 7799–7811.

    Article  CAS  PubMed  Google Scholar 

  51. Valcarcel D, Martino R, Caballero D, Mateos MV, Perez-Simon JA, Canals C et al. Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 2003; 31: 387–392.

    Article  CAS  PubMed  Google Scholar 

  52. Bornhauser M, Thiede C, Platzbecker U, Jenke A, Helwig A, Plettig R et al. Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clin Cancer Res 2001; 7: 2254–2262.

    CAS  PubMed  Google Scholar 

  53. Maris MB, Niederwieser D, Sandmaier BM, Storer B, Stuart M, Maloney D et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003; 102: 2021–2030.

    Article  CAS  PubMed  Google Scholar 

  54. Baron F, Maris MB, Storer BE, Sandmaier BM, Stuart MJ, McSweeney PA et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia. Biol Blood Marrow Transplant 2005; 11: 272–279.

    Article  PubMed  Google Scholar 

  55. Kerbauy FR, Storb R, Hegenbart U, Gooley T, Shizuru J, Al-Ali HK et al. Hematopoietic cell transplantation from HLA-identical sibling donors after low-dose radiation-based conditioning for treatment of CML. Leukemia 2005; 19: 990–997.

    Article  CAS  PubMed  Google Scholar 

  56. Girgis M, Hallemeier C, Blum W, Brown R, Lin H-S, Khoury H et al. Chimerism and clinical outcomes of 110 unrelated donor bone marrow transplants who underwent conditioning with low-dose, single-exposure total body irradiation and cyclophosphamide. Blood 2005; 105: 3035–3041.

    Article  CAS  PubMed  Google Scholar 

  57. Wilson H-MP, Lesnikov V, Plymate SR, Ward J, Deeg HJ . High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis. Leukemia 2005; 19: 580–585.

    Article  CAS  PubMed  Google Scholar 

  58. Faucher C, Mohty M, Vey N, Gaugler B, Bilger K, Moziconnacci MJ et al. Bone marrow as stem cell source for allogeneic HLA-identical sibling transplantation following reduced-intensity preparative regimen. Exp Hematol 2003; 31: 873–880.

    Article  PubMed  Google Scholar 

  59. Cao TM, Shizuru JA, Wong RM, Sheehan K, Laport GG, Stockerl-Goldstein KE et al. Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose. Blood 2005; 105: 2300–2306.

    Article  CAS  PubMed  Google Scholar 

  60. Baron F, Maris MB, Storer BE, Sandmaier BM, Panse JP, Chauncey TR et al. High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation. Leukemia 2005; 19: 822–828.

    Article  CAS  PubMed  Google Scholar 

  61. Maris MB, Sandmaier BM, Storer BE, Maloney DG, Shizuru JA, Agura E et al. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing. Biol Blood Marrow Transplant 2006; 12: 454–465.

    Article  CAS  PubMed  Google Scholar 

  62. Giaccone L, McCune JS, Maris MB, Gooley TA, Sandmaier BM, Slattery JT et al. Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Blood 2005; 106: 4381–4388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Matthes-Martin S, Lion T, Haas OA, Frommlet F, Daxberger H, Konig M et al. Lineage-specific chimaerism after stem cell transplantation in children following reduced intensity conditioning: potential predictive value of NK cell chimaerism for late graft rejection. Leukemia 2003; 17: 1934–1942.

    Article  CAS  PubMed  Google Scholar 

  64. Devetten MP, Vose JM . Graft-versus-host disease: how to translate new insights into new therapeutic strategies (Review). Biol Blood Marrow Transplant 2004; 10: 815–825.

    Article  PubMed  Google Scholar 

  65. Mohty M, Blaise D, Faucher C, Vey N, Bouabdallah R, Stoppa A-M et al. Inflammatory cytokines and acute graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2005; 106: 4407–4411.

    Article  CAS  PubMed  Google Scholar 

  66. Pelot MR, Pearson DA, Swenson K, Zhao G, Sachs J, Yang Y-G et al. Lymphohematopoietic graft-vs-host reactions can be induced without graft-vs-host disease in murine mixed chimeras established with a cyclophosphamide-based nonmyeloablative conditioning regimen. Biol Blood Marrow Transplant 1999; 5: 133–143.

    Article  CAS  PubMed  Google Scholar 

  67. Baron F, Little M-T, Storb R . Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning. Blood Rev 2005; 19: 153–164.

    Article  PubMed  Google Scholar 

  68. Mielcarek M, Martin PJ, Leisenring W, Flowers MED, Maloney DG, Sandmaier BM et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756–762.

    Article  CAS  PubMed  Google Scholar 

  69. Couriel DR, Saliba RM, Giralt S, Khouri I, Andersson B, de Lima M et al. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant 2004; 10: 178–185.

    Article  PubMed  Google Scholar 

  70. Sorror M, Maris M, Diaconescu R, Storb R . Lessened severe graft-versus-host after ‘minitransplantations’ (Letter to the Editor). Blood 2005; 105: 2614.

    Article  CAS  PubMed  Google Scholar 

  71. Aoudjhane M, Labopin M, Gorin NC, Shimoni A, Ruutu T, Kolb H-J et al. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia 2005; 19: 2304–2312.

    Article  CAS  PubMed  Google Scholar 

  72. Scott BL, Sandmaier BM, Storer B, Maris MB, Sorror ML, Maloney DG et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 2006; 20: 128–135.

    Article  CAS  PubMed  Google Scholar 

  73. Perez-Simon JA, Diez-Campelo M, Martino R, Sureda A, Caballero D, Canizo C et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation. Blood 2003; 102: 1108–1113.

    Article  CAS  PubMed  Google Scholar 

  74. Mattsson J, Uzunel M, Brune M, Hentschke P, Barkholt L, Stierner U et al. Mixed chimaerism is common at the time of acute graft-versus-host disease and disease response in patients receiving non-myeloablative conditioning and allogeneic stem cell transplantation. Br J Haematol 2001; 115: 935–944.

    Article  CAS  PubMed  Google Scholar 

  75. Perez-Simon JA, Caballero D, Diez-Campelo M, Lopez-Perez R, Mateos G, Canizo C et al. Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation (Review). Leukemia 2002; 16: 1423–1431.

    Article  CAS  PubMed  Google Scholar 

  76. Uzunel M, Mattsson J, Brune M, Johansson JE, Aschan J, Ringden O . Kinetics of minimal residual disease and chimerism in patients with chronic myeloid leukemia after nonmyeloablative conditioning and allogeneic stem cell transplantation. Blood 2003; 101: 469–472.

    Article  CAS  PubMed  Google Scholar 

  77. Keil F, Prinz E, Moser K, Mannhalter C, Kalhs P, Worel N et al. Rapid establishment of long-term culture-initiating cells of donor origin after nonmyeloablative allogeneic hematopoietic stem-cell transplantation, and significant prognostic impact of donor T-cell chimerism on stable engraftment and progression-free survival. Transplantation 2003; 76: 230–236.

    Article  CAS  PubMed  Google Scholar 

  78. Passweg JR, Tichelli A, Meyer-Monard S, Heim D, Stern M, Kuhne T et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia 2004; 18: 1835–1838.

    Article  CAS  PubMed  Google Scholar 

  79. Marks DI, Parker A, Robinson SP . Donor lymphocyte infusions after reduced intensity conditioning allogeneic transplantation: what we need to know. Blood 2004; 104: 295–296.

    Article  CAS  PubMed  Google Scholar 

  80. Lange T, Deininger M, Brand R, Hegenbart U, Al-Ali H, Krahl R et al. BCR-ABL transcripts are early predictors for hematological relapse in chronic myeloid leukemia after hematopoietic cell transplantation with reduced intensity conditioning. Leukemia 2004; 18: 1468–1475.

    Article  CAS  PubMed  Google Scholar 

  81. van Leeuwen JE, van Tol MJ, Joosten AM, Wijnen JT, Verweij PJ, Khan PM et al. Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse. Blood 1994; 83: 3059–3067.

    CAS  PubMed  Google Scholar 

  82. Wu CJ, Krishnamurti L, Kutok JL, Biernacki M, Rogers S, Zhang W et al. Evidence for ineffective erythropoiesis in severe sickle cell disease. Blood 2005; 106: 3639–3645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bethge WA, Hegenbart U, Stuart MJ, Storer BE, Maris MB, Flowers MED et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Blood 2004; 103: 790–795.

    Article  CAS  PubMed  Google Scholar 

  84. Peggs KS, Thomson K, Hart H, Geary J, Morris EC, Yong K et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism and disease responses. Blood 2004; 103: 1548–1556.

    Article  CAS  PubMed  Google Scholar 

  85. Sala-Torra O, Hanna C, Loken MR, Flowers MED, Maris M, Ladne PA et al. Evidence of donor-derived hematologic malignancies after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006; 12: 511–517.

    Article  PubMed  Google Scholar 

  86. Baron F, Dresse MF, Beguin Y . Transmission of chronic myeloid leukemia through peripheral-blood stem-cell transplantation. N Engl J Med 2003; 349: 913–914.

    Article  PubMed  Google Scholar 

  87. Auffermann-Gretzinger S, Lossos IS, Vayntrub TA, Leong W, Grumet FC, Blume KG et al. Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients. Blood 2002; 99: 1442–1448.

    Article  CAS  PubMed  Google Scholar 

  88. Boeck S, Hamann M, Pihusch V, Heller T, Diem H, Rolf B et al. Kinetics of dendritic cell chimerism and T cell chimerism in allogeneic hematopoietic stem cell recipients. Bone Marrow Transplant 2006; 37: 57–64.

    Article  CAS  PubMed  Google Scholar 

  89. Collin MP, Hart DN, Jackson GH, Cook G, Cavet J, Mackinnon S et al. The fate of human Langerhans cells in hematopoietic stem cell transplantation. J Exp Med 2006; 203: 27–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mohty M, Blaise D, Faucher C, Bardou VJ, Gastaut JA, Viens P et al. Impact of plasmacytoid dendritic cells on outcome after reduced-intensity conditioning allogeneic stem cell transplantation. Leukemia 2005; 19: 1–6.

    Article  CAS  PubMed  Google Scholar 

  91. Poloni A, Leoni P, Buscemi L, Balducci F, Pasquini R, Masia MC et al. Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen. Leukemia 2006; 20: 329–335.

    Article  CAS  PubMed  Google Scholar 

  92. Rezvani K, Mielke S, Ahmadzadeh M, Kilical Y, Savani BN, Zeilah J et al. High donor Foxp3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic stem cell transplantation (SCT). Blood; prepublished online Apr 2006; doi: 10.1182/blood-2206-02-003996.

  93. Sykes M, Preffer F, McAfee S, Saidman SL, Weymouth D, Andrews DM et al. Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation. Lancet 1999; 353: 1755–1759.

    Article  CAS  PubMed  Google Scholar 

  94. Dahmen UM, Boettcher M, Krawczyk M, Broelsch CE . Flow cytometric ‘rare event analysis’: a standardized approach to the analysis of donor cell chimerism. J Immunol Methods 2002; 262: 53–69.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We acknowledge Barry Storer for help with the figures. We thank Helen Crawford, Bonnie Larson, and Sue Carbonneau for help with this paper preparation. We are grateful to Heather Hildebrant and Deborah Bassuk for data processing, the research nurses Mary Hinds, Michelle Bouvier and John Sedgwick, and the medical nursing and clinical staffs for their dedicated care of the patients. This work was supported by grants CA78902, CA18029, CA15704, DK42716, and HL36444 of the National Institutes of Health, Bethesda, MD. FB is research associate of the National Fund for Scientific Research (FNRS) Belgium and supported in part by postdoctoral grants from the Fulbright Commission and from the Centre Anticancereux près l'ULg.

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  1. Clinical Research Division, Transplantation Biology Programme, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    F Baron & B M Sandmaier

  2. Department of Hematology, University of Liège, Liège, Belgium

    F Baron

  3. Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA

    B M Sandmaier

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  1. F Baron
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  2. B M Sandmaier
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Correspondence to B M Sandmaier.

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Baron, F., Sandmaier, B. Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Leukemia 20, 1690–1700 (2006). https://doi.org/10.1038/sj.leu.2404335

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  • DOI: https://doi.org/10.1038/sj.leu.2404335

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