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Stem Cell Procurement

Hourly monitoring of circulating CD34+ cells to optimize timing of autologous apheresis in pediatric patients

Summary:

In order to increase the CD34+ cell yield in children undergoing autologous stem cell transplantation, the optimum time of apheresis after G-CSF administration has still to be found. We prospectively studied the mobilization of CD34+ cells and white blood cells in the peripheral blood (PB) of 20 pediatric patients before leukapheresis. The monitoring schedule covered 12 h, with blood samples taken before and at 2, 4, 5, 6, 7, 8, 10 and 12 h after G-CSF administration when 10 CD34+ cells/μl were reached. CD34+ cells were measured by flow cytometric analysis both in the single- and dual-platform setting. Two different patterns of mobilization (POM) emerged: 12 patients showed an increase in CD34+ cells in PB during the first 4 h after G-CSF (POM I), while eight patients had an initial decrease of CD34+ cells. However, all patients together showed a significant increase of CD34+ cells about 10 h after G-CSF administration. Further studies with more patients, using an enhanced monitoring schedule will be required to refine the results.

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References

  1. Gale RP, Henon P, Juttmer C . Blood stem cell transplants come of age. Bone Marrow Transplant 1992; 9: 151–157.

    CAS  PubMed  Google Scholar 

  2. Leibundgut K, Hirt A, Luthy AR et al. Autotransplants with peripheral blood stem cells and clinical results obtained in children: a review. Eur J Pediatr 1993; 152: 546–554.

    Article  CAS  PubMed  Google Scholar 

  3. Diaz MA, Vincent M, Garcia-Sanchez F et al. Long term hematopoietic engraftment after autologous peripheral blood progenitor cell transplantation in pediatric patients: effect of the CD34+ cell dose. Vox Sanguinis 2000; 79: 145–150.

    Article  CAS  PubMed  Google Scholar 

  4. Handgretinger R, Lang P, Ihm K et al. Isolation and transplantation of highly purified autologous peripheral CD34+ progenitor cells: purging efficacy, hematopoietic reconstitution and long-term outcome in children with high-risk neuroblastoma. Bone Marrow Transplant 2002; 29: 731–736.

    Article  CAS  PubMed  Google Scholar 

  5. Armitage S, Hargreaves R, Samson D et al. CD34 counts to predict the adequate collection of peripheral blood progenitor cells. Bone Marrow Transplant 1998; 22: 215–216.

    Article  Google Scholar 

  6. Demirer T, Ilhan O, Ayli M et al. Monitoring of peripheral blood CD34+ cell counts on the first day of apheresis is highly predictive for efficient CD34+ cell yield. Therapeut Apheresis 2002; 6: 384–389.

    Article  Google Scholar 

  7. Fontao-Wendel R, Lazar A, Melges S et al. The absolute number of circulating CD34+ cells is the best predictor of peripheral hematopoietic stem cell yield. J Hematother 1999; 8: 255–262.

    Article  CAS  PubMed  Google Scholar 

  8. Locatelli F, Perotti C, Zecca M, Pedrazzoli P . Transplantation of peripheral blood stem cells mobilized by haematopoietic growth factors in childhood. Bone Marrow Transplant 1998; 22 (Suppl. 2): S51–S55.

    PubMed  Google Scholar 

  9. Remes K, Matinlauri I, Grenman S et al. Daily measurements of blood CD34+ cells after stem cell mobilization predict stem cell yield and posttransplant hematopoietic recovery. Hematotherapy 1997; 6: 13–19.

    Article  CAS  Google Scholar 

  10. Urashima M, Kato Y, Hoshi Y et al. Factors affecting the efficiency of peripheral blood stem cell collection in children treated with chemotherapy and G-CSF. Acta Paediatr Jpn 1994; 36: 156–161.

    Article  CAS  PubMed  Google Scholar 

  11. Yu J, Leisenring W, Bensinger WI, Holmberg LA . The predictive value of white cell or CD34+ cell count in the peripheral blood for timing of apheresis and maximizing yield. Transfusion 1999; 39: 442–450.

    Article  CAS  PubMed  Google Scholar 

  12. Kasparu H, Krieger O, Girschikofsky M et al. Factors influencing the timing of peripheral blood stem cell collection (PBSC). Transfus Sci 1996; 17: 595–600.

    Article  CAS  PubMed  Google Scholar 

  13. Knudsen LM, Gaarsdal E, Jensen L et al. Improved priming for mobilization of and optimal timing for harvest of peripheral blood stem cells. J Hematother 1996; 5: 399–406.

    Article  CAS  PubMed  Google Scholar 

  14. To LB, Shepperd M, Haylock DN et al. Single high doses of cyclophosphamide enable the collection of high numbers of hemopoietic stem cells from the peripheral blood. Exp Hematol 1990; 18: 442–447.

    CAS  PubMed  Google Scholar 

  15. Bensinger W, Appelbaum F, Rowley S et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Onc 1995; 13: 2547–2555.

    Article  CAS  Google Scholar 

  16. Weaver CH, Birch R, Greco FA, Schwartzberg L . Mobiliza tion and harvesting of peripheral blood stem cells: randomized evaluations of different doses of filgrastim. Br J Haemat 1998; 100: 338–347.

    Article  CAS  Google Scholar 

  17. Demeocq F, Kanold J, Chassagne J et al. Successful blood stem cell collection and transplantation in children weighing less than 25 kg. Bone Marrow Transplant 1994; 13: 45–50.

    Google Scholar 

  18. Fischmeister G, Kurz M, Haas OA et al. G-CSF versus GM-CSF for stimulation of peripheral blood progenitor cells (PBSC) and leukocytes in healthy volunteers: comparison of efficacy and tolerability. Ann Hematol 1999; 78: 117–123.

    Article  CAS  PubMed  Google Scholar 

  19. Lydaki E, Bolonaki E, Stiakaki E et al. Efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte-macrophage colony-stimulating factor in neutropenic children with malignancies. Pediatr Hematol Oncol 1995; 12: 551–558.

    Article  CAS  PubMed  Google Scholar 

  20. Diaz MA, Villa M, Allegre A et al. Collection and transplantation of peripheral blood progenitor cells mobilized by G-CSF alone in children with malignancies. Br J Haematol 1996; 96: 148–154.

    Article  Google Scholar 

  21. Smolowicz AG, Villman K, Berlin G, Tidefelt U . Kinetics of peripheral blood stem cell harvests during a single apheresis. Transfusion 1999; 39: 403–409.

    Article  CAS  PubMed  Google Scholar 

  22. Dreger P, Schmitz N . Stem cell mobilization in healthy donors: current status. Infus Ther Transf Med 1999; 26: 92–95.

    Google Scholar 

  23. Jilma B, Hergovich N, Stohlawetz P et al. Circadian variation of granulocyte colony stimulating factor levels in man. Br J Haematol 1999; 106: 368–370.

    Article  CAS  PubMed  Google Scholar 

  24. Abrahamsen JF, SmSaaland R, Sothern RB, Laerum OD . Variation in cell yield and proliferative activity of positive selected human CD34+ bone marrow cells along the circadian time scale. Eur J Haematol 1998; 60: 7–15.

    Article  CAS  PubMed  Google Scholar 

  25. Kiefer T, Kalusche EM, Schüler F, Hutzschenreuter U . Circadian variations of circulating CD34+ cell numbers after chemotherapy plus G-CSF in patients with breast cancer. Onkologie 1997; 20: 344, abstract (DÖGHO).

    Google Scholar 

  26. Köchling G, Legat D, Weber BE et al. Circadian variations of CD34+ cell-concentrations following mobilization with chemotherapy and filgrastim. Onkologie 1997; 20: 343; abstract (DÖGHO).

    Google Scholar 

  27. Sato N, Sawada K, Takahashi TA et al. A time course study for optimal harvest of peripheral blood progenitor cells by granulocyte colony-stimulating factor in healthy volunteers. Exp Hematol 1994; 22: 973–978.

    CAS  PubMed  Google Scholar 

  28. Sekhsaria S, Fleisher TA, Vowells S et al. Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase-deficient severe combined immunodeficiency disease patients. Blood 1996; 88: 1104–1112.

    CAS  PubMed  Google Scholar 

  29. Stroncek DF, Clay ME, Herr G et al. The kinetics of G-CSF mobilization of CD34+ cells in healthy people. Transf Med 1997; 7: 19–24.

    Article  CAS  Google Scholar 

  30. Watts MJ, Addison I, Ings SJ, Long SG . Optimal timing for collection of PBPC after glycosylated G-CSF administration. Bone Marrow Transplant 1998; 21: 365–368.

    Article  CAS  PubMed  Google Scholar 

  31. Fischer J, Unkrig U, Ackermann M, Frick M . Intra-day CD34+ cell counts depend on the timing to administration and correlate with the resulting G-CSF plasma level after steady-state mobilization of PBPC by filgrastim. Blood 1994; 84: 81; abstract (ASH).

    Google Scholar 

  32. Bjarnson GA, Reis M, Robinson JB et al. Circadian variation in CD34+ count and response to G-CSF therapy in healthy volunteers: implication for harvesting efficacy. Blood 1996; 87: 1568; abstract #368-III (ASH).

    Google Scholar 

  33. Sutherland DR, Anderson L, Keeney M et al. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. J Hematother 1996; 5: 213–225.

    Article  CAS  PubMed  Google Scholar 

  34. Moretti S, Dabusti M, Castagnari B et al. Comparison of single and dual platform methodologies for the estimation of CD34+ hematopoietic progenitor cells: correlation with colony assay. Int J Biol Markers 2002; 17: 259–267.

    Article  CAS  PubMed  Google Scholar 

  35. Barbosa IL, Sousa ME, Godinho MI et al. Single- versus dual-platform assays for human CD34+ cell enumeration. Cytometry 1999; 38: 274–279.

    Article  CAS  PubMed  Google Scholar 

  36. Lefrere F, Bernard M, Audat F, Cavazzana-Calvo M . Comparison of lenograstim vs filgrastim administration following chemotherapy for peripheral blood stem cell (PBSC) collection: a retrospective study of 126 patients. Leuk Lymphoma 1999; 35: 501–505.

    Article  CAS  PubMed  Google Scholar 

  37. Martinez C, Sureda A, Martino R, Cancelas JA . Efficient peripheral blood stem cell mobilization with low-dose G-CSF (50 μg/m2) after salvage chemotherapy for lymphoma. Bone Marrow Transplant 1997; 20: 855–858.

    Article  CAS  PubMed  Google Scholar 

  38. Arbona C, Prosper F, Benet I, Mena F . Comparison between once a day vs twice a day G-CSF for mobilization of peripheral blood progenitor cells in normal donors for allogenic PBPC transplantation. Bone Marrow Transplant 1998; 22: 39–45.

    Article  CAS  PubMed  Google Scholar 

  39. Kröger N, Zeller W, Hassan TH, Krüger W . Schedule-dependency of G-CSF in peripheral blood progenitor cell mobilization in breast cancer patients. Blood 1998; 91: 828–830.

    Google Scholar 

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Acknowledgements

We thank all patients and their parents for their compliance and support. Further thanks go to ‘Verein Hilfe für krebskranke Kinder Frankfurt e.V.’ for supporting this study.

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Correspondence to U Koehl.

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Bochennek, K., Andreas, C., Margraf, C. et al. Hourly monitoring of circulating CD34+ cells to optimize timing of autologous apheresis in pediatric patients. Bone Marrow Transplant 36, 481–489 (2005). https://doi.org/10.1038/sj.bmt.1705098

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