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Myeloid Progenitor Cells

Flow cytometric detection of growth factor receptors in autografts and analysis of growth factor concentrations in autologous stem cell transplantation: possible significance for platelet recovery

Abstract

In order to improve prediction of hematopoietic recovery, we conducted a pilot study, analyzing the significance of growth factor receptor expression in autografts as well as endogenous growth factor levels in blood before, during and after stem cell transplantation. Three early acting (stem cell factor (SCF), Flt3 ligand (Flt3) and fetal antigen 1 (FA1)) and three lineage-specific growth factors (EPO, G-CSF and thrombopoietin (Tpo)) were analyzed by ELISA in 16 patients with multiple myeloma (MM) and 16 patients with non-Hodgkin's lymphoma (NHL). The relative number of SCF, Flt3, Tpo and G-CSF receptor positive, CD34+ progenitor cells were measured by flow cytometry in the leukapheresis product used for transplantation in a subgroup of 15 patients (NHL, n = 8, MM, n = 7). Three factors were identified as having a significant impact on platelet recovery. First, the level of Tpo in blood at the time of the nadir (day +7). Second, the percentage of re-infused thrombopoietin receptor positive progenitors and finally, the percentage of Flt3 receptor positive progenitors. On the other hand, none of the analyzed factors significantly predicted myeloid or erythroid recovery. These findings need to be confirmed in prospectively designed studies. Bone Marrow Transplantation (2000) 26, 525–531.

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References

  1. Testa U, Fossati C, Samoggia P et al. Expression of growth factor receptors in unilineage differentiation culture of purified hematopoietic progenitors Blood 1996 88: 3391–3406

    CAS  PubMed  Google Scholar 

  2. Olweus J, Terstappen LWMM, Thompson PA, Lund-Johansen F . Expression and function of receptors for stem cell factor and erythropoietin during lineage commitment of human hematopoietic progenitor cells Blood 1996 88: 1594–1607

    CAS  PubMed  Google Scholar 

  3. Zeigler FC, Bennett BD, Jordan CT et al. Cellular and molecular characterization of the role of FLK-2/FLT-3 receptor tyrosine kinase in hematopoietic stem cells Blood 1994 84: 2422–2430

    CAS  PubMed  Google Scholar 

  4. Jensen CH, Krogh TN, Højrup P et al. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2 Eur J Biochem 1994 225: 83–92

    Article  CAS  Google Scholar 

  5. Moore KA, Pytowski B, Witte L et al. Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs Proc Natl Acad Sci USA 1997 94: 4011–4016

    Article  CAS  Google Scholar 

  6. Testa U, Martucci R, Rutella S et al. Autologous stem cell transplantation: release of early and late acting growth factors relates with hematopoietic ablation and recovery Blood 1994 84: 3532–3539

    CAS  PubMed  Google Scholar 

  7. McKinstry WJ, Li C-L, Rasko JEJ et al. Cytokine receptor expression on hematopoietic stem and progenitor cells Blood 1997 89: 65–71

    CAS  PubMed  Google Scholar 

  8. Shimoda K, Okamura S, Harada N et al. High-frequency granuloid colony-forming ability of G-CSF receptor possessing CD34 antigen positive human umbilical cord blood hematopoietic progenitors Exp Hematol 1995 23: 226–228

    CAS  PubMed  Google Scholar 

  9. Nichol JL, Hokom MM, Hornkol A et al. Megakaryocyte growth and development factor. Analyses of in vitro effects on human megakaryopoiesis and endogenous serum levels during chemotherapy-induced thrombocytopenia J Clin Invest 1995 95: 2973–2978

    Article  CAS  Google Scholar 

  10. Solar GP, Kerr WG, Zeigler FC et al. Role of c-Mpl in early hematopoiesis Blood 1998 92: 4–10

    CAS  PubMed  Google Scholar 

  11. Schiødt I, Bergmann OJ, Johnsen HE, Hansen NE . Early infections after autologous transplantation for haematological malignancies Med Oncol 1998 15: 103–108

    Article  Google Scholar 

  12. Cairo MS, Suen Y, Sender L et al. Circulating granulocyte colony-stimulating factor (G-CSF) levels after allogeneic and autologous bone marrow transplantation: endogenous G-CSF production correlates with myeloid engraftment Blood 1992 79: 1869–1873

    CAS  PubMed  Google Scholar 

  13. Schapira L, Antin JH, Ransil BJ et al. Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy Blood 1990 76: 2354–2359

    CAS  PubMed  Google Scholar 

  14. Shimazaki C, Inaba T, Uchiyama H et al. Serum thrombopoietin levels in patients undergoing autologous peripheral blood stem cell transplantation Bone Marrow Transplant 1997 19: 771–775

    Article  CAS  Google Scholar 

  15. 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  Google Scholar 

  16. Johnsen HE, Knudsen LM for the Nordic Stem Cell Laboratory Group (NSCL-G) . Nordic flow cytometry standards for CD34+ cell enumeration in blood and leukapheresis products: report from the second Nordic workshop J Hematother 1996 5: 237–245

    Article  CAS  Google Scholar 

  17. Jensen CH, Krogh TN, Støving RK et al. Fetal antigen 1 (FA1), a circulating member of the epidermal growth factor (EGF) superfamily: ELISA development, physiology and metabolism in relation to renal function Clin Chim Acta 1997 268: 1–20

    Article  CAS  Google Scholar 

  18. Knudsen LM, Hansen SW, Daugaard G et al. Comparison of rhG-CSF primed bone marrow and blood stem cell autografts: an analysis of engraftment in malignant lymphomas and solid tumours Eur J Haematol 1998 61: 229–234

    Article  CAS  Google Scholar 

  19. Johnsen HE, Rasmussen T, Knudsen LM . CD34+ subset and tumor cell quantitation by flow cytometry – step toward quality assessment of autografts in B cell malignancies Vox Sang 1998 74: (Suppl.2) 477–482

    Article  CAS  Google Scholar 

  20. Nagata Y, Shozaki Y, Nagahisa H et al. Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis Thromb Haemostasis 1997 77: 808–814

    Article  CAS  Google Scholar 

  21. Testa U, Rutella S, Martucci R et al. Autologous stem cell transplantation: evaluation of erythropoietic reconstitution by highly fluorescent reticulocyte counts, erythropoietin, soluble transferrin receptors, ferritin, TIBC and iron dosages Br J Haematol 1997 96: 762–775

    Article  CAS  Google Scholar 

  22. Busch FW, Pilgrim TB, Krämer A, Ehninger G . Plasma levels of granulocyte colony-stimulating factor in patients after allogeneic bone marrow transplantation for chronic myeloid leukemia correlate with engraftment of transplanted marrow Bone Marrow Transplant 1997 19: 653–659

    Article  CAS  Google Scholar 

  23. Miksits K, Beyer J, Siegert W . Serum concentrations of G-CSF during high-dose chemotherapy with autologous stem cell rescue Bone Marrow Transplant 1993 11: 375–377

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from Dagmar Marshall's Foundation, Anders Hasselbalch's Foundation for Defeating Leukemia and Director Jacob Madsen and Wife Olga Madsen's Foundation.

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Schiødt, I., Jensen, C., Kjærsgaard, E. et al. Flow cytometric detection of growth factor receptors in autografts and analysis of growth factor concentrations in autologous stem cell transplantation: possible significance for platelet recovery. Bone Marrow Transplant 26, 525–531 (2000). https://doi.org/10.1038/sj.bmt.1702554

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