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The impact of leukapheresis on immune-cell number and function in patients with advanced cancer

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Abstract

Background

Leukapheresis is often performed in cancer patients to harvest stem cells, manufacture therapeutic vaccines, or follow immunologic response to therapy. We have recently described the minimal impact of leukapheresis on normal donors. Here we provide additional immunologic data from patients with advanced cancer who underwent leukapheresis.

Methods

Using data from cancer patients on clinical trials who had leukapheresis (n = 64) or peripheral blood draws only (n = 90) as controls for immune analysis, we evaluated the impact of leukapheresis on number and function of lymphocytes.

Results

In the leukapheresis group, median age was 63.5 (range 38–82); 87.5 % were male. Comparing pre- and post-leukapheresis values within the groups, with each patient as its own control, there was no significant difference in enzyme-linked immunosorbent spot (ELISPOT), antivector humoral response, absolute lymphocyte count (ALC), or T cell number. Twelve patients completed three leukaphereses with subsequent ELISPOT analysis; seven had increased responses to flu (1.1- to 2.3-fold) with an even distribution around no change. Nineteen patients had matched ALC values after completing three leukaphereses with no significant change from baseline.

Conclusions

These data provide evidence that leukapheresis has no detectable effects on a cancer patient’s immune system in terms of number or function. These results contribute to a growing body of evidence refuting the hypothesis that a patient’s immune competence is meaningfully affected by the procedure. Limitations include a restriction to 2-L leukapheresis procedure and small sample size.

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Abbreviations

ALC:

Absolute lymphocyte count

CAP:

College of American Pathologists

CLIA:

Clinical Laboratory Improvement Act

ELISA:

Enzyme-linked immunosorbent assay

ELISPOT:

Enzyme-linked immunosorbent spot

FDA:

US Food and Drug Administration

IFN-γ:

Interferon-gamma

IgG:

Immunoglobulin G

NIH:

National Institutes of Health

OS:

Overall survival

PBMCs:

Peripheral blood mononuclear cells

References

  1. Guidance for industry and FDA review staff: collection of platelets by automated methods. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/ucm062946.pdf. Accessed 22 Apr 2014

  2. European Directorate for the Quality of Medicines and Healthcare (2010) Guide to the preparation, use and quality assurance of blood components, 16th edn. http://www.centronazionalesangue.it/sites/default/files/guida_edqm_16_edizione.pdf. Accessed 22 Apr 2014

  3. Standards for blood banks and transfusion services, 26th edn., Summary of significant changes. http://www.aabb.org/sa/standards/documents/sigchngstds26.pdf. Accessed 22 Apr 2014

  4. Blum KS, Pabst R (2007) Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs? Immunol Lett 108(1):45–51

    Article  CAS  PubMed  Google Scholar 

  5. Strauss RG (1994) Effects on donors of repeated leukocyte losses during plateletpheresis. J Clin Apher 9(2):130–134

    Article  CAS  PubMed  Google Scholar 

  6. Kolf C, Bolan C, Wesley R, Browning J, Leitman SF (2003) Sustained decreases in lymphocyte counts in serial long-term leukapheresis donors. Transfusion 43(9s):28a

    Google Scholar 

  7. Gulley JL, Leitman SF, Dahut W, Schlom J (2012) Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst 104(14):1106 author reply 1109–1112

    Article  PubMed  Google Scholar 

  8. Castelo-Branco C, Soveral I (2014) The immune system and aging: a review. Gynecol Endocrinol 30(1):16–22

    Article  CAS  PubMed  Google Scholar 

  9. Arlen PM, Gulley JL, Todd N, Lieberman R, Steinberg SM, Morin S, Bastian A, Marte J, Tsang KY, Beetham P, Grosenbach DW, Schlom J, Dahut W (2005) Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer. J Urol 174(2):539–546

    Article  CAS  PubMed  Google Scholar 

  10. Gulley JL, Arlen PM, Bastian A, Morin S, Marte J, Beetham P, Tsang KY, Yokokawa J, Hodge JW, Menard C, Camphausen K, Coleman CN, Sullivan F, Steinberg SM, Schlom J, Dahut W (2005) Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res 11(9):3353–3362

    Article  CAS  PubMed  Google Scholar 

  11. Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, Dahut W (2006) A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 12(4):1260–1269

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Arlen PM, Skarupa L, Pazdur M, Seetharam M, Tsang KY, Grosenbach DW, Feldman J, Poole DJ, Litzinger M, Steinberg SM, Jones E, Chen C, Marte J, Parnes H, Wright J, Dahut W, Schlom J, Gulley JL (2007) Clinical safety of a viral vector based prostate cancer vaccine strategy. J Urol 178(4 Pt 1):1515–1520

    Article  CAS  PubMed  Google Scholar 

  13. Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW, Cereda V, Vergati M, Steinberg SM, Halabi S, Jones E, Chen C, Parnes H, Wright JJ, Dahut WL, Schlom J (2010) Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother 59(5):663–674

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Gulley JL, Arlen PM, Tsang KY, Yokokawa J, Palena C, Poole DJ, Remondo C, Cereda V, Jones JL, Pazdur MP, Higgins JP, Hodge JW, Steinberg SM, Kotz H, Dahut WL, Schlom J (2008) Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin Cancer Res 14(10):3060–3069

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Madan RA, Mohebtash M, Arlen PM, Vergati M, Rauckhorst M, Steinberg SM, Tsang KY, Poole DJ, Parnes HL, Wright JJ, Dahut WL, Schlom J, Gulley JL (2012) Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol 13(5):501–508

    Article  CAS  PubMed  Google Scholar 

  16. Madan RA, Tsang KY, Bilusic M, Vergati M, Poole DJ, Jochems C, Tucker JA, Schlom J, Giaccone G, Gulley JL (2013) Effect of talactoferrin alfa on the immune system in adults with non-small cell lung cancer. Oncologist 18(7):821–822

    Article  PubMed Central  PubMed  Google Scholar 

  17. Bilusic M, Heery CR, Arlen PM, Rauckhorst M, Apelian D, Tsang KY, Tucker JA, Jochems C, Schlom J, Gulley JL, Madan RA (2014) Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother 63(3):225–234

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Marshall JL, Gulley JL, Arlen PM, Beetham PK, Tsang KY, Slack R, Hodge JW, Doren S, Grosenbach DW, Hwang J, Fox E, Odogwu L, Park S, Panicali D, Schlom J (2005) Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. J Clin Oncol 23(4):720–731

    Article  CAS  PubMed  Google Scholar 

  19. von Mehren M, Arlen P, Gulley J, Rogatko A, Cooper HS, Meropol NJ, Alpaugh RK, Davey M, McLaughlin S, Beard MT, Tsang KY, Schlom J, Weiner LM (2001) The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma. Clin Cancer Res 7(5):1181–1191

    Google Scholar 

  20. von Mehren M, Arlen P, Tsang KY, Rogatko A, Meropol N, Cooper HS, Davey M, McLaughlin S, Schlom J, Weiner LM (2000) Pilot study of a dual gene recombinant avipox vaccine containing both carcinoembryonic antigen (CEA) and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas. Clin Cancer Res 6(6):2219–2228

    Google Scholar 

  21. Effect of talactoferrin in adults with non-small cell lung cancer. http://clinicaltrials.gov/show/NCT00923741. Accessed 22 Apr 2014

  22. An open label phase I study to eval the safety and tolerability of a vaccine (GI-6207) consisting of whole, heat-killed recombinant saccharomyces cerevisiae (Yeast) genetically modified to express CEA protein in adults with metastatic CEA-expressing carcinoma. http://clinicaltrials.gov/show/NCT00924092. Accessed 22 Apr 2014

  23. Vaccine therapy with PROSTVAC/TRICOM and flutamide versus flutamide alone to treat prostate cancer. http://clinicaltrials.gov/show/NCT00450463. Accessed 22 Apr 2014

  24. Gulley J, Chen AP, Dahut W, Arlen PM, Bastian A, Steinberg SM, Tsang K, Panicali D, Poole D, Schlom J, Michael Hamilton J (2002) Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer. Prostate 53(2):109–117

    Article  CAS  PubMed  Google Scholar 

  25. Huber ML, Haynes L, Parker C, Iversen P (2012) Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst 104(4):273–279

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Kantoff PW, Higano CS, Small EJ, Whitmore JB, Frohlich MW, Schellhammer PF (2012) Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst 104(14):1107–1109 author reply 1109–1112

    Article  PubMed  Google Scholar 

  27. Drake CG (2012) Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst 104(18):1422 author reply 1422–1423

    Article  PubMed  Google Scholar 

  28. Mark D, Samson D, Bonnell C, Ziegler K, Aronson N (2014) Outcomes of sipuleucel-T therapy: technology assessment report. http://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id77TA.pdf. Accessed 22 Apr 2014

  29. Sheikh NA, Petrylak D, Kantoff PW, Dela Rosa C, Stewart FP, Kuan LY, Whitmore JB, Trager JB, Poehlein CH, Frohlich MW, Urdal DL (2013) Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunol Immunother 62(1):137–147

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research for their support of this study. We also express appreciation to the professionals at the NIH Clinical Center Department of Transfusion Medicine for their part in performing apheresis procedures in study patients and to the medical oncology fellows at the NCI for their attention to patient care. Finally, we thank Bonnie L. Casey and Debra Weingarten for their editorial assistance in the preparation of this manuscript. This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.

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Correspondence to James L. Gulley.

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Gulley, J.L., Marté, J., Heery, C.R. et al. The impact of leukapheresis on immune-cell number and function in patients with advanced cancer. Cancer Immunol Immunother 64, 1429–1435 (2015). https://doi.org/10.1007/s00262-015-1738-9

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  • DOI: https://doi.org/10.1007/s00262-015-1738-9

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