Skip to main content

Advertisement

SpringerLink
Log in

Granulocyte collection by polymorphonuclear cell-targeting apheresis with medium-molecular-weight hydroxyethyl starch

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Granulocyte transfusion (GTX) is a therapeutic option for patients with prolonged neutropenia suffering from severe infections. Efficient granulocyte collection by apheresis from donors requires clear separation of granulocytes from red blood cells (RBCs), and infusion of high-molecular-weight (MW) hydroxyethyl starch (HES) facilitates RBC sedimentation. Recent research has shown that apheresis with medium-MW HES may prevent adverse effects of high-MW HES on donors, but the rationale for collection with medium-MW HES has yet to be evaluated. To validate the use of medium-MW HES, we first performed experiments with whole blood samples to determine how efficiently high-, medium- and low-MW HES separated granulocytes from RBCs, and found that medium-MW HES was just as efficient as high-MW HES. We also reviewed clinical data of granulocyte apheresis at our institution to evaluate granulocyte yields. Retrospective analysis of granulocyte collection revealed that apheresis with medium-MW HES yielded sufficient granulocytes for GTX and that donor anemia reduced collection efficiency. These results collectively may help us to establish a safer method for apheresis targeting polymorphonuclear granulocytes as an alternative to high-MW HES.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pizzo PA. Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med. 1993;328(18):1323–32. https://doi.org/10.1056/NEJM199305063281808.

    Article  CAS  PubMed  Google Scholar 

  2. Robenshtok E, Gafter-Gvili A, Goldberg E, Weinberger M, Yeshurun M, Leibovici L, et al. Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis. J Clin Oncol. 2007;25(34):5471–89. https://doi.org/10.1200/JCO.2007.12.3851.

    Article  CAS  PubMed  Google Scholar 

  3. Miles-Jay A, Butler-Wu S, Rowhani-Rahbar A, Pergam SA. Incidence rate of fluoroquinolone-resistant gram-negative rod bacteremia among allogeneic hematopoietic cell transplantation patients during an era of levofloxacin prophylaxis. Biol Blood Marrow Transplant. 2015;21(3):539–45. https://doi.org/10.1016/j.bbmt.2014.12.006.

    Article  PubMed  Google Scholar 

  4. El-Mahallawy HA, El-Wakil M, Moneer MM, Shalaby L. Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer. Pediatr Blood Cancer. 2011;57(2):283–8. https://doi.org/10.1002/pbc.22926.

    Article  PubMed  Google Scholar 

  5. Rolston KV. The use of new and better antibiotics for bacterial infections in patients with leukemia. Clin Lymphoma Myeloma. 2009;9(Suppl 3):S357–63. https://doi.org/10.3816/CLM.2009.s.035.

    Article  PubMed  Google Scholar 

  6. Peters C. Granulocyte transfusions in neutropenic patients: beneficial effects proven? Vox Sang. 2009;96(4):275–83. https://doi.org/10.1111/j.1423-0410.2008.01159.x.

    Article  CAS  PubMed  Google Scholar 

  7. Kadri SS, Remy KE, Strich JR, Gea-Banacloche J, Leitman SF. Role of granulocyte transfusions in invasive fusariosis: systematic review and single-center experience. Transfusion. 2015;55(9):2076–85. https://doi.org/10.1111/trf.13099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kerr JP, Liakopolou E, Brown J, Cornish JM, Fleming D, Massey E, et al. The use of stimulated granulocyte transfusions to prevent recurrence of past severe infections after allogeneic stem cell transplantation. Br J Haematol. 2003;123(1):114–8. https://doi.org/10.1046/j.1365-2141.2003.04583.x.

    Article  PubMed  Google Scholar 

  9. Price TH, Boeckh M, Harrison RW, McCullough J, Ness PM, Strauss RG, et al. Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection. Blood. 2015;126(18):2153–61. https://doi.org/10.1182/blood-2015-05-645986.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhou B, Song T, Feng Y, Zhu Z, Chang W, Liu Y, et al. Clinical outcome of granulocyte transfusion therapy for the treatment of refractory infection in neutropenic patients with hematological diseases. Ann Hematol. 2018;97(11):2061–70. https://doi.org/10.1007/s00277-018-3432-4.

    Article  PubMed  Google Scholar 

  11. Bux J, Cassens U, Dielschneider T, Duchscherer M, Edel E, Eichler H, et al. Tolerance of granulocyte donors towards granulocyte colony-stimulating factor stimulation and of patients towards granulocyte transfusions: results of a multicentre study. Vox Sang. 2003;85(4):322–5. https://doi.org/10.1111/j.0042-9007.2003.00373.x.

    Article  CAS  PubMed  Google Scholar 

  12. Strauss RG. Therapeutic granulocyte transfusions in 1993. Blood. 1993;81(7):1675–8.

    Article  CAS  Google Scholar 

  13. Caspar CB, Seger RA, Burger J, Gmür J. Effective stimulation of donors for granulocyte transfusions with recombinant methionyl granulocyte colony-stimulating factor. Blood. 1993;81(11):2866–71.

    Article  CAS  Google Scholar 

  14. Bensinger WI, Price TH, Dale DC, Appelbaum FR, Clift R, Lilleby K, et al. The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis. Blood. 1993;81(7):1883–8.

    Article  CAS  Google Scholar 

  15. Liles WC, Huang JE, Llewellyn C, SenGupta D, Price TH, Dale DC. A comparative trial of granulocyte-colony-stimulating factor and dexamethasone, separately and in combination, for the mobilization of neutrophils in the peripheral blood of normal volunteers. Transfusion. 1997;37(2):182–7. https://doi.org/10.1046/j.1537-2995.1997.37297203521.x.

    Article  CAS  PubMed  Google Scholar 

  16. Stroncek DF, Yau YY, Oblitas J, Leitman SF. Administration of G-CSF plus dexamethasone produces greater granulocyte concentrate yields while causing no more donor toxicity than G–CSF alone. Transfusion. 2001;41(8):1037–44. https://doi.org/10.1046/j.1537-2995.2001.41081037.x.

    Article  CAS  PubMed  Google Scholar 

  17. Ikemoto J, Yoshihara S, Fujioka T, Ohtsuka Y, Fujita N, Kokubunji A, et al. Impact of the mobilization regimen and the harvesting technique on the granulocyte yield in healthy donors for granulocyte transfusion therapy. Transfusion. 2012;52(12):2646–52. https://doi.org/10.1111/j.1537-2995.2012.03661.x.

    Article  PubMed  Google Scholar 

  18. Cancelas JA, Padmanabhan A, Le T, Ambruso DR, Rugg N, Worsham DN, et al. Spectra Optia granulocyte apheresis collections result in higher collection efficiency of viable, functional neutrophils in a randomized, crossover, multicenter trial. Transfusion. 2015;55(4):748–55. https://doi.org/10.1111/trf.12907.

    Article  CAS  PubMed  Google Scholar 

  19. Leitner GC, Kolovratova V, Horvath M, Worel N. Granulocyte collection using a novel apheresis system eases the procedure and provides concentrates of high quality. Transfusion. 2015;55(5):991–5. https://doi.org/10.1111/trf.12928.

    Article  CAS  PubMed  Google Scholar 

  20. Janes AW, Mishler JM, Lowes B. Serial infusion effects of hydroxyethyl starch on ESR, blood typing and crossmatching and serum amylase levels. Vox Sang. 1977;32(3):131–4. https://doi.org/10.1111/j.1423-0410.1977.tb00617.x.

    Article  CAS  PubMed  Google Scholar 

  21. Lee JH, Leitman SF, Klein HG. A controlled comparison of the efficacy of hetastarch and pentastarch in granulocyte collections by centrifugal leukapheresis. Blood. 1995;86(12):4662–6.

    Article  CAS  Google Scholar 

  22. Strauss RG, Klein HG, Leitman SF, Price TH, Lichtiger B, Martinez F, et al. Preparation of granulocyte concentrates by apheresis: collection modalities in the USA. Vox Sang. 2011;100(4):426–33. https://doi.org/10.1111/j.1423-0410.2010.01417.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358(2):125–39. https://doi.org/10.1056/NEJMoa070716.

    Article  CAS  PubMed  Google Scholar 

  24. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Åneman A, et al. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med. 2012;367(2):124–34. https://doi.org/10.1056/NEJMoa1204242.

    Article  CAS  PubMed  Google Scholar 

  25. Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367(20):1901–11. https://doi.org/10.1056/NEJMoa1209759.

    Article  CAS  PubMed  Google Scholar 

  26. Auwerda JJ, Wilson JH, Sonneveld P. Foamy macrophage syndrome due to hydroxyethyl starch replacement: a severe side effect in plasmapheresis. Ann Intern Med. 2002;137(12):1013–4. https://doi.org/10.7326/0003-4819-137-12-200212170-00037.

    Article  PubMed  Google Scholar 

  27. Auwerda JJ, Leebeek FW, Wilson JH, van Diggelen OP, Lam KH, Sonneveld P. Acquired lysosomal storage caused by frequent plasmapheresis procedures with hydroxyethyl starch. Transfusion. 2006;46(10):1705–11. https://doi.org/10.1111/j.1537-2995.2006.00962.x.

    Article  CAS  PubMed  Google Scholar 

  28. Mayor S. EMA confirms that hydroxyethyl starch solutions should not be used in critically ill, sepsis, or burns patients. BMJ. 2013;347:f6197. https://doi.org/10.1136/bmj.f6197.

  29. US Food and Drug Administration. FDA Safety Communication: Boxed Warning on increased mortality and severe renal injury, and additional warning on risk of bleeding, for use of hydroxyethyl starch solutions in some settings. 2013. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm358271.htm.

  30. European Medicines Agency. Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients. 2018. https://www.ema.europa.eu/en/news/hydroxyethyl-starch-solutions-cmdh-introduces-newmeasures-protect-patients.

  31. Gandhi SD, Weiskopf RB, Jungheinrich C, Koorn R, Miller D, Shangraw RE, et al. Volume replacement therapy during major orthopedic surgery using Voluven (hydroxyethyl starch 130/04) or hetastarch. Anesthesiology. 2007;106(6):1120–7. https://doi.org/10.1097/01.anes.0000265422.07864.37.

    Article  CAS  PubMed  Google Scholar 

  32. Nanya M, Yurugi K, Kato I, Hiramatsu H, Kawabata H, Kondo T, et al. Successful granulocyte apheresis using medium molecular weight hydroxyethyl starch. Int J Hematol. 2019;110(6):729–35. https://doi.org/10.1007/s12185-019-02755-2.

    Article  PubMed  Google Scholar 

  33. Thorausch K, Schulz M, Bialleck H, Luxembourg B, Seifried E, Bonig H. Granulocyte collections: comparison of two apheresis systems. Transfusion. 2013;53(12):3262–8. https://doi.org/10.1111/trf.12197.

    Article  CAS  PubMed  Google Scholar 

  34. Doblinger N, Bredthauer A, Mohrez M, Hähnel V, Graf B, Gruber M, et al. Impact of hydroxyethyl starch and modified fluid gelatin on granulocyte phenotype and function. Transfusion. 2019;59(6):2121–30. https://doi.org/10.1111/trf.15279.

    Article  CAS  PubMed  Google Scholar 

  35. Dullinger K, Pamler I, Brosig A, Mohrez M, Hähnel V, Offner R, et al. Granulocytapheresis with modified fluid gelatin versus high-molecular-weight hydroxyethyl starch: a matched-pair analysis. Transfusion. 2017;57(2):397–403. https://doi.org/10.1111/trf.13898.

    Article  CAS  PubMed  Google Scholar 

  36. Kamezaki K, Miyamoto T, Henzan T, Numata A, Iwasaki H, Nagafuji K, et al. Collection of mobilized peripheral blood stem cells from a donor with severe iron deficient anemia. J Clin Apher. 2007;22(5):292–4. https://doi.org/10.1002/jca.20141.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the technical staffs at Center for Cellular and Molecular Medicine and the clinical engineering technologists at Department of Medical Technology, Kyushu University Hospital for assistance with procedure of apheresis. We also thank the apheresis nurses at Blood Transfusion Center, Kyushu University Hospital for clinical care contributions.

Author information

Authors and Affiliations

  1. Center for Cellular and Molecular Medicine, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Tomoko Henzan, Takuji Yamauchi, Ikumi Yamanaka, Teppei Sakoda, Yuichiro Semba, Masayasu Hayashi, Yoshikane Kikushige, Takahiro Maeda & Yuya Kunisaki

  2. Department of Medical Technology, Kyushu University Hospital, Fukuoka, 812-8582, Japan

    Hiroyuki Mishima

  3. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Masataka Ishimura, Yuhki Koga & Shouichi Ohga

  4. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan

    Toshihiro Miyamoto & Koichi Akashi

  5. Division of Precision Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan

    Takahiro Maeda

Authors
  1. Tomoko Henzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takuji Yamauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ikumi Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teppei Sakoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuichiro Semba
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masayasu Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshikane Kikushige
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroyuki Mishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masataka Ishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yuhki Koga
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Toshihiro Miyamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shouichi Ohga
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Koichi Akashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takahiro Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yuya Kunisaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuya Kunisaki.

Ethics declarations

Conflict of interest

The authors declare no competing financial interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henzan, T., Yamauchi, T., Yamanaka, I. et al. Granulocyte collection by polymorphonuclear cell-targeting apheresis with medium-molecular-weight hydroxyethyl starch. Int J Hematol 114, 691–700 (2021). https://doi.org/10.1007/s12185-021-03207-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-021-03207-6

Keywords

Search

Navigation