Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Immune Reconstitution

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

Bone Marrow Transplantation volume 30, pages 571–578 (2002)Cite this article

Abstract

This study evaluated the effects of low-dose IL-2 plus G-CSF/EPO on post-PBSC transplantation (PBSCT) immune-hematopoietic reconstitution and NK activity in patients with breast (BrCa) and ovarian cancer (OvCa). To this end, two consecutive series of patients were prospectively assigned to distinct post-PBSCT cytokine regimens (from day +1 to day +12) which consisted of G-CSF (5 μg/kg/day) plus EPO (150 IU/kg/every other day) in 17 patients (13 BrCa and 4 OvCa) or G-CSF/EPO plus IL-2 (2 × 105 IU/m2/day) in 15 patients (10 BrCa and 5 OvCa). Hematopoietic recovery and post-transplantation clinical courses were comparable in G-CSF/EPO- and in G-CSF/EPO plus IL-2-treated patients, without significant side-effects attributable to IL-2 administration. In the early and late post-transplant period a significantly higher PMN count was observed in G-CSF/EPO plus IL-2-treated patients (P = 0.034 and P = 0.040 on day +20 and +100, respectively). No significant differences were found between the two groups of patients in the kinetics of most lymphocyte subsets except naive CD45RA+ T cells which had a delayed recovery in G-CSF/EPO plus IL-2 patients (P = 0.021 on day +100). No significant difference was observed between NK activity in the two different groups, albeit a significantly higher NK count was observed in G-CSF/EPO plus IL-2 series on day +20 (P = 0.020). These results demonstrate that low-dose IL-2 can be safely administered in combination with G-CSF/EPO early after PBSCT and that it exerts favorable effects on post-PBSCT myeloid reconstitution, but not on immune recovery.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Pujade-Lauraine E, Curè H, Battista C et al. High dose chemotherapy in ovarian cancer Int J Gynecol Cancer 2001 11 (Suppl.1): 64 67

    Article  Google Scholar 

  2. Salerno MG, Ferrandina G, Greggi S et al. High-dose chemotherapy as a consolidation approach in advanced ovarian cancer: long-term results Bone Marrow Transplant 2001 27: 1017 1025

    Article  CAS  Google Scholar 

  3. Coleman RE . High dose chemotherapy. Rationale and results in breast carcinoma Cancer 2000 88: (Suppl.) 3059 3064

    Article  CAS  Google Scholar 

  4. Rodenhuis S, Richel DJ, van der Wall E et al. Randomised trial of high-dose chemotherapy and hematopoietic progenitor cell support in operable breast cancer with extensive axillary lymph node involvment Lancet 1998 352: 515 521

    Article  CAS  Google Scholar 

  5. Guillaume T, Rubinstein DB, Symann M . Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation Blood 1998 92: 1471 1490

    CAS  Google Scholar 

  6. Ueno NT, Rondòn G, Mirza NQ et al. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer J Clin Oncol 1998 16: 986 993

    Article  CAS  Google Scholar 

  7. Bay JO, Choufi B, Pomel C et al. Potential allogeneic graft-versus-tumor effect in a patient with ovarian cancer Bone Marrow Transplant 2000 25: 681 682

    Article  CAS  Google Scholar 

  8. Pierelli L, Perillo A, Ferrandina G et al. The role of growth factor administration and T cell recovery after peripheral blood progenitor cell transplantation in the treatment of solid tumors: results from a randomized comparison of G-CSF and GM-CSF Transfusion 2001 41: 1577 1585

    Article  CAS  Google Scholar 

  9. van der Burg ME, van Lent M, Buyse M et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer New Engl J Med 1995 332: 629 634

    Article  CAS  Google Scholar 

  10. Benedetti Panici P, Pierelli L, Scambia G et al. High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-hematological, hematological toxicities and role of growth factor administration Br J Cancer 1997 75: 1205 1212

    Article  CAS  Google Scholar 

  11. Pierelli L, Perillo A, Greggi S et al. Erythropoietin addition to granulocyte colony-stimulating factor abrogates life-threatening neutropenia and increases peripheral-blood progenitor-cell mobilization after epirubicin, paclitaxel, and cisplatin combination chemotherapy: results of a randomized comparison J Clin Oncol 1999 17: 1288 1295

    Article  CAS  Google Scholar 

  12. Pierelli L, Leone G, Cortesi E et al. Docetaxel and epirubicin plus G-CSF mobilize hematopoietic progenitors in breast cancer Ann Oncol 1999 10: 1531 1532 (letter)

    Article  CAS  Google Scholar 

  13. Pierelli L, Menichella G, Scambia G et al. In vitro and in vivo effects of recombinant human erythropoietin plus recombinant G-CSF on human hematopoietic progenitor cells Bone Marrow Transplant 1994 14: 23 30

    CAS  Google Scholar 

  14. Cascinu S, Fedeli A, Del Ferro E et al. Recombinant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo J Clin Oncol 1994 12: 1058 1062

    Article  CAS  Google Scholar 

  15. Pene R, Appelbaum FR, Fisher K et al. Use of granulocyte–macrophage colony-stimulating factor and erythropoietin in combination after autologous marrow transplantation Bone Marrow Transplant 1993 11: 219 222

    CAS  PubMed  Google Scholar 

  16. 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 

  17. Pacifici R, Zuccaro P, Cozzi-Lepre A et al. Quantification of the variation due to lysing technique in immunophenotyping of healthy and HIV-infected individuals Clin Biochem 1998 31: 165 172

    Article  CAS  Google Scholar 

  18. Scambia G, Benedetti Panici P, Pierelli L et al. Immunological reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation for advanced ovarian cancer Eur J Cancer 1993 29A: 1518 1522

    Article  CAS  Google Scholar 

  19. Peters WP, Ross M, Vredenburgh JJ et al. High-dose chemotherapy and autologous bone marrow support as consolidation after standard dose adjuvant therapy for high-risk primary breast cancer J Clin Oncol 1993 11: 1132 1143

    Article  CAS  Google Scholar 

  20. Gianni AM, Siena S, Bregni M et al. Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five year results J Clin Oncol 1997 15: 2312 2321

    Article  CAS  Google Scholar 

  21. Hortobagy GN, Buzdar AU, Theriault RL et al. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma J Natl Cancer Inst 2000 92: 225 233

    Article  Google Scholar 

  22. Bergh J, Wiklund T, Erikstein B et al. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomized trial. Scandinavian Breast Group 9401 study Lancet 2000 356: 1384 1391

    Article  CAS  Google Scholar 

  23. Porrata LF, Gertz MA, Inwards DJ et al. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma Blood 2001 98: 579 585

    Article  CAS  Google Scholar 

  24. Porrata LF, Ingle JN, Litzow MR et al. Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer Bone Marrow Transplant 2001 28: 865 871

    Article  CAS  Google Scholar 

  25. Pierelli L, Bonanno G, Rutella S et al. CD105 (Endoglin) expression on hematopoietic stem/progenitor cells Leuk Lymphoma 2001 42: 1195 1206

    Article  CAS  Google Scholar 

  26. Laughlin MJ, Kirkpatrick G, Sabiston N et al. Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy and autologous bone marrow support in patients in phase-I clinical trials of colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF Ann Hematol 1993 67: 267 276

    Article  CAS  Google Scholar 

  27. Meehan KR, Arun B, Gehan EA et al. Immunotherapy with interleukin-2 and α-interferon after IL-2-activated hematopoietic stem cell transplantation for breast cancer Bone Marrow Transplant 1999 23: 667 673

    Article  CAS  Google Scholar 

  28. Heslop HE, Duncombe AS, Reittie JE et al. Interleukin 2 infusion induces haemopoietic growth factors and modifies marrow regeneration after chemotherapy or autologous marrow transplantation Br J Haematol 1991 77: 237 244

    Article  CAS  Google Scholar 

  29. Toh HC, McAfee SL, Sackstein R et al. High-dose cyclophosphamide + carboplatin and interleukin-2 (IL-2) activated autologous stem cell transplantation followed by maintenance IL-2 therapy in metastatic breast carcinoma – a phase II study Bone Marrow Transplant 2000 25: 19 24

    Article  CAS  Google Scholar 

  30. Aladdin H, Larsen CS, Moller BK et al. Effect of subcutaneous interleukin-2 therapy on phenotype and function of peripheral blood mononuclear cells in human immunodeficiency virus infected patients Scand J Immunol 2000 51: 168 175

    Article  CAS  Google Scholar 

  31. Toren A, Nagler A, Rozenfeld-Granot G et al. Amplification of immunological functions by subcutaneous injection of intermediate-high dose interleukin-2 for 2 years after autologous stem cell transplantation in children with stage IV neuroblastoma Transplantation 2000 70: 1100 1104

    Article  CAS  Google Scholar 

  32. Vlk V, Eckschlager T, Kavan P et al. Clinical ineffectiveness of IL-2 and/or IFN alpha administration after autologous PBSC transplantation in pediatric oncological patients Pediatr Hematol Oncol 2000 17: 31 44

    Article  CAS  Google Scholar 

  33. Aladdin H, Larsen CS, Schjerling P et al. Effects of subcutaneous IL-2 therapy on telomere lengths in PBMC in HIV-infected patients Scand J Immunol 2001 53: 315 319

    Article  CAS  Google Scholar 

  34. Rutella S, Pierelli L, Bonanno G et al. Immune reconstitution after autologous peripheral blood progenitor cell transplantation: effect of interleukin-15 on T-cell survival and effector functions Exp Hematol 2001 29: 1503 1516

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynaecology and Obstetrics, Catholic University of the Sacred Heart, Rome, Italy

    A Perillo, A Battaglia, MG Salerno, A Fattorossi, S Mancuso & G Scambia

  2. Haematology and Haemotransfusion Service, Catholic University of the Sacred Heart, Rome, Italy

    L Pierelli, S Rutella & G Leone

  3. Department of Experimental Medicine, ‘La Sapienza’ University, Rome, Italy

    E Cortesi

  4. Haematology, ‘S Camillo-Forlanini’ Hospital, Rome, Italy

    L De Rosa & M Lalle

  5. Division of Medical Oncology, ‘S Vincenzo’ Hospital, Taormina, Italy

    F Ferraù

Authors
  1. A Perillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Pierelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. MG Salerno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Rutella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Cortesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Fattorossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L De Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F Ferraù
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Lalle
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. G Leone
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S Mancuso
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. G Scambia
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perillo, A., Pierelli, L., Battaglia, A. et al. Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer. Bone Marrow Transplant 30, 571–578 (2002). https://doi.org/10.1038/sj.bmt.1703687

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703687

Keywords

This article is cited by

Search

Advanced search

Quick links