Advertisement

Annals of Hematology

, Volume 86, Issue 8, pp 591–598 | Cite as

Viable CD34+/CD133+ blood progenitor cell dose as a predictor of haematopoietic engraftment in multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation

  • C. HicksEmail author
  • R. Wong
  • A. Manoharan
  • Y. L. Kwan
Original Article

Abstract

Both CD34 (cluster of differentiation 34) and the more recently described CD133 are markers of primitive stem cells with haematopoietic repopulating ability. Most transplanting centres use a minimum number of CD34+ cells as the requirement for a transplant and consider this a predictor of haematopoietic engraftment. However, transplanted CD34+ cell dose does not always give a close correlation with time to engraftment nor explain delayed engraftment in some patients. We have retrospectively evaluated the potential of measuring viable CD133+ cell numbers in the autograft as an alternative predictor of haematological engraftment after autologous stem-cell transplantation in a cohort of patients with multiple myeloma (MM). We found an average 32% loss of viability of CD34+ cells in the post-thaw sample compared with the fresh sample. Of the original estimated CD34+ cell numbers transplanted per kg, 43% of the thawed samples were double positive for CD34+/CD133+. In this patient group, the CD34+/CD133+ subset gave the closest statistical correlation with time to neutrophil engraftment (p < 0.05), particularly for patients given above median (1.8 × 106/kg) dose of the double-positive cells. The CD34+/CD133+ population was the only parameter to give a significant correlation with white cell engraftment in this patient cohort (p < 0.05). There was no significant correlation between CD34+, viable CD34+ or viable CD34+/CD133+ cells/kilogram with platelet engraftment. Determination of viable CD34+/CD133+ progenitor cell dose in the autograft may be a useful tool to predict neutrophil recovery after autologous transplantation than conventional assessment of CD34+ numbers. These results warrant further investigation of the role of CD133 in haematopoietic engraftment.

Keywords

CD34 CD133 Stem cells Haematopoiesis Engraftment Multiple myeloma 

Notes

Acknowledgement

Dr. Alhossain Abdallah and Dr. Freda Passam, St. George Hospital Haematology registrar and visiting staff specialist, respectively, for the statistical correlation and helpful discussions. Thanks also to Sue Smith for her technical assistance and helpful discussions with the flow cytometry.

References

  1. 1.
    To LB, Haycock DN, Simmons PJ, Juttner CA (1997) The biology and clinical uses of blood stem cells. Blood 89:2233–2258PubMedGoogle Scholar
  2. 2.
    Bender JG, To LB, Williams S, Schwartzberg LS (1992) Defining a therapeutic dose of peripheral blood stem cells. J Hematother 1:329–341PubMedGoogle Scholar
  3. 3.
    Villalon L, Odriozola J, Larana JG, Zamora C, Perez de Oteyza J, Jodra MH et al (2000) Autologous peripheral blood progenitor cell transplantation with <2 × 10(6) CD34 (+)/kg: an analysis of variables concerning mobilisation and engraftment. Hematol J 1:374–381PubMedCrossRefGoogle Scholar
  4. 4.
    Shpall EJ, Champlin R, Glaspy JA (1998) Effect of CD34+ peripheral blood progenitor cell dose on haematopoietic recovery. Biol Blood Marrow Transplant 4:84–92PubMedCrossRefGoogle Scholar
  5. 5.
    Sator M, Antonenas V, Garvan F, Webb M, Bradstock KF (2005) Recovery of viable CD34+ cells from cryopreserved hemopoietic progenitor cell products. Bone Marrow Transplant 36:199–204CrossRefGoogle Scholar
  6. 6.
    Abrahamsen JF, Wentzel-Larsen T and Bruserud O (2004) Autologous transplantation: the viable transplanted CD34+ cell dose measured post-thaw does not predict engraftment kinetics better than the total CD34+ cell dose measured pre-freeze in patients that receive more than 2 × 10(6) CD34+ cells/kg. Cytotherapy 6:356–362Google Scholar
  7. 7.
    Allan DS, Keeney M, Howson-Jan K, Popma J, Weir K, Bhatia M, Sutherland DR et al (2002) Number of viable CD34+ cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 29:967–972PubMedCrossRefGoogle Scholar
  8. 8.
    Pecora AL, Preti RA, Gleim GW, Jennis A, Zahos K, Cantwell S et al (1998) CD34+CD33− cells influence days to engraftment and transfusion requirements in autologous blood stem-cell recipients. J Clin Oncol 16:2093–2104PubMedGoogle Scholar
  9. 9.
    Watanabe T, Dave B, Heimann DG, Jackson JD, Kessinger A, Talmadge JE (1998) Cell adhesion molecule expression on CD34+ cells in grafts and time to myeloid and platelet recovery after autologous stem cell transplantation. Exp Hematol 26:10–18PubMedGoogle Scholar
  10. 10.
    Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG et al (1997) AC133, a novel marker for human haematopoietic stem and progenitor cells. Blood 90:5002–5012PubMedGoogle Scholar
  11. 11.
    Pasino M, Lanza T, Marotta F, Scarso L, De Biasio P, Amato S et al (2000) Flow cytometric and functional characterisation of AC133(+) cells from human umbilical cord blood. Br J Haematol 108:793–800PubMedCrossRefGoogle Scholar
  12. 12.
    Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT et al (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterisation and molecular cloning. Blood 90:5013–5021PubMedGoogle Scholar
  13. 13.
    Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M et al (2000) Expression of VEGFR-2 and AC133 by circulating human CD 34 (+) cells identifies a population of functional endothelial precursors. Blood 95:952–958PubMedGoogle Scholar
  14. 14.
    Padovan CS, Jahn K, Birnbaum T, Reich P, Sostak P, Strupp M et al (2003) Expression of neuronal markers in differentiated marrow stromal cells and CD133+ stem-like cells. Cell Transplant 12:839–848PubMedGoogle Scholar
  15. 15.
    Bitan M, Shapira MY, Resnick IB, Zilberman I, Miron S, Samuel S et al (2005) Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133+ purified stem cells. Exp Hematol 33:713–718PubMedCrossRefGoogle Scholar
  16. 16.
    Lang P, Bader P, Schumm M, Feuchtinger T, Einsele H, Fuhrer M et al (2004) Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors. Br J Hematother Stem Cell Res 12:23–32Google Scholar
  17. 17.
    Trickett AE, Smith S, Kwan YL (2001) Accurate calculation of blood volume to be processed by aphaeresis to achieve target CD34+ cell numbers or PBPC transplantation. Cytotherapy 3:5–10PubMedCrossRefGoogle Scholar
  18. 18.
    Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR (1998) Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 34:61–70PubMedCrossRefGoogle Scholar
  19. 19.
    Sasaki DT, Dumas SE, Engleman EG (1987) Discrimination of viable and non-viable cells using propidium iodide in two color immunofluorescence. Cytometry 8:213–420Google Scholar
  20. 20.
    Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al (1995) An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myoablative chemotherapy. Blood 86:3961–3969PubMedGoogle Scholar
  21. 21.
    Besinger W, Applebaum F, Rowley S, Storb R, Sanders J, Lilleby K et al (1995) Factors that influence collection and engraftment of autologous peripheral blood stem cells. J Clin Oncol 13:2547–2555Google Scholar
  22. 22.
    Haas R, Witt B, Mohle R, Goldschmidt H, Hohaus S, Fruehauf S et al (1995) Sustained long-term haematopoiesis after myeloablative therapy with peripheral blood progenitor support. Blood 85:3754–3761PubMedGoogle Scholar
  23. 23.
    Ketterer N, Salles G, Raba M, Espinouse D, Sonet A, Tremisi P et al (1998) High CD34(+) counts decrease hematological toxicity of autologous peripheral blood progenitor cell transplantation. Blood 91:3148–3155PubMedGoogle Scholar
  24. 24.
    Jansen J, Thompson JM, Dugan MJ, Nolan P, Weimann MC, Birhiray R et al (2002) Peripheral blood progenitor cell transplantation. Ther Apher 6:5–14PubMedCrossRefGoogle Scholar
  25. 25.
    Olivieri A, Offidani M, Montanari M, Ciniero L, Ombrosi L, Masia CM et al (1998) Factors affecting haemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: a single center experience. Haematologica 83:329–337PubMedGoogle Scholar
  26. 26.
    Tricot G, Jagannath D, Nelson J, Tindle S, Miller L, Cheson B et al (1995) Peripheral blood stem cell transplants for multiple myeloma: identification of favourable variables for rapid engraftment in 225 patients. Blood 85:588–596PubMedGoogle Scholar
  27. 27.
    Yang H, Acker JP, Cabuhat M, Letcher B, Larratt L, McGann LE (2005) Association of post-thaw viable CD34+cells and CFU-GM with time to haematopoietic engraftment. Bone Marrow Transplant 35:881–887PubMedCrossRefGoogle Scholar
  28. 28.
    Matsumoto K, Yasui K, Yamashita N, Horie Y, Yamada T, Tani Y et al (2000) In vitro proliferation potential of AC133 positive cells in peripheral blood. Stem Cells 18:196–203PubMedCrossRefGoogle Scholar
  29. 29.
    Kuci S, Wessels JT, Buhring HJ, Schilbach K, Schumm M, Seitz G et al (2003) Identification of a novel class of human adherent CD34-stem cells that give rise to SCID-repopulating cells. Blood 101:869–876PubMedCrossRefGoogle Scholar
  30. 30.
    Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R et al (2006) Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoeitic stem cells. Blood 107:2162–2169PubMedCrossRefGoogle Scholar
  31. 31.
    Lefrere F, Delarue R, Levy V, Damaj G, Tu A, Porcher R et al (2002) High dose-CD34+cells are not clinically relevant in reducing cytopenia and blood component consumption following myeloablative therapy and peripheral blood progenitor cell transplantation as compared with standard dose. Transfusion 42:443–450PubMedCrossRefGoogle Scholar
  32. 32.
    Hass R, Mohle R, Fruhauf S et al (1994) Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. Blood 83:3787–3794Google Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Clinical HaematologyBone Marrow Transplant Laboratory, St. George HospitalSydneyAustralia
  2. 2.Department of HaematologySouth East Area Laboratory ServicesSydneyAustralia

Personalised recommendations