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Treatment-related mortality following autologous hematopoietic stem cell transplantation is unaffected by timing of G-CSF administration

Bone Marrow Transplantation volume 55, pages 1697–1700 (2020)Cite this article

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High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (ASCT) is a standard consolidation therapy for multiple myeloma and lymphoma. Prolonged neutropenia and serious infections can be associated with significant morbidity and mortality in these patients. Granulocyte-colony stimulating factors (G-CSFs) have clinically demonstrated to accelerate neutrophil engraftment after ASCT by up to 7 days [1,2,3]. The American Society of Clinical Oncology (ASCO) recommends starting G-CSF 1–3 days after high-dose chemotherapy and ASCT, and continuing until the absolute neutrophil count (ANC) is ≥2000–3000 × 106/L [4]. Despite evidence to support the use of G-CSF to expedite neutrophil recovery, lack of consensus with respect to optimal timing of G-CSF initiation exists in the transplant community and varies among different practices. Recently, there has been a growing body of interest in late (≥day +5) G-CSF initiation after ASCT primarily for cost-effectiveness but also because growth factor-responsive neutrophilic precursors are not yet formed immediately after stem cell infusion [5]. Studies compared early (day 0 to day +4) with late (≥day +5) G-CSF initiation after ASCT with mixed results regarding neutrophil engraftment, platelet recovery or number of febrile days [6,7,8,9,10]. Furthermore, individualized or ANC-driven G-CSF administration did not affect outcome [11, 12]. Lastly, the usefulness of G-CSF in patients who receive >5 × 106 CD34+ cells/kg is also unclear.

A clinical practice change was adopted at our institution in November 2016, where all patients undergoing ASCT initiated G-CSF on day +5 (late G-CSF initiation cohort), whereas those prior to November 2016 initiated on the day of transplantation (early G-CSF initiation cohort). The primary objective of this retrospective study was to compare time to neutrophil engraftment between these two cohorts. Secondary objectives included infectious complications, length of hospital stay, treatment-related mortality, and G-CSF cost difference. The study was approved by Institutional Review Board (IRB). All consecutive patients aged ≥18 years with plasma cell neoplasm and lymphoma, who underwent ASCT from January 2015 to June 2018, were evaluated. Patients received high-dose chemotherapy and peripherally mobilized stem cells inpatient. Both cohorts received filgrastim (Neupogen, Amgen) at a dose of 5 µg/kg/day (rounded off to the nearest vial strength; 300 µg or 480 µg). Patients weighing > 100 kg received filgrastim at a dose of 600 µg/day. Filgrastim was continued until ANC was ≥ 1000 × 106/L for at least 24 hours. Supportive measures including anti-infective prophylaxis and transfusion of blood products were in accordance with institutional standardized operating procedures and did not change during the study period.

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References

  1. McQuaker IG, Hunter AE, Pacey S, Haynes AP, Iqbal A, Russell NH. Low-dose filgrastim significantly enhances neutrophil recovery following autologous peripheral-blood stem cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit. J Clin Oncol. 1997;15:451–7.

    Article  CAS  Google Scholar 

  2. Schmitz N, Ljungman P, Cordonnier C, Kempf C, Linkesch W, Alegre A, et al. Lenograstim after autologous peripheral blood progenitor cell transplantation: results of a double blind, randomized trial. Bone Marrow Transplant. 2004;34:955–62.

    Article  CAS  Google Scholar 

  3. Trifilio S, Zhou Z, Galvin J, Fong JL, Monreal J, Mehta J. Filgrastim versus TBO-filgrastim to reduce the duration of neutropenia after autologous hematopoietic stem cell transplantation: TBO, or not TBO, that is the question. Clin Transplant 2015;29(Dec):1128–32.

    Article  CAS  Google Scholar 

  4. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33:3199–212.

    Article  CAS  Google Scholar 

  5. Metcalf D. Control of granulocytes and macrophages: molecular, cellular, and clinical aspects. Science 1991;254:529–33.

    Article  CAS  Google Scholar 

  6. Demirer T, Ayli M, Dagli M, Haznedar R, Genc Y, Fen T, et al. Influence of post-transplant recombinant human granulocyte colony-stimulating factor administration on peritransplant morbidity in patients undergoing autologous stem cell transplantation. Br J Haematol. 2002;118:1104–11.

    Article  CAS  Google Scholar 

  7. Piccirillo N, Sica S, Laurenti L, Chiusolo P, La Barbera EO, Sora F, et al. Optimal timing of G-CSF administration after CD34+ immunoselected peripheral blood progenitor cell transplantation. Bone Marrow Transplant. 1999;23:1245–50.

    Article  CAS  Google Scholar 

  8. de Azevedo AM, Nucci M, Maiolino A, Vigorito AC, Simoes BP, Aranha FJ, et al. A randomized, multicenter study of GCSF starting on day +1 vs day +5 after autologous peripheral blood progenitor cell transplantation. Bone Marrow Transplant. 2002;29:745–51.

    Article  Google Scholar 

  9. Bence-Bruckler I, Bredeson C, Atkins H, McDiarmid S, Hamelin L, Hopkins H, et al. A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation. Bone Marrow Transplant. 1998;22:965–9.

    Article  CAS  Google Scholar 

  10. Cottini F, Sborov D, Yu KC, Lamprecht M, Tackett K, Li J, Devine SM, Poi M, Phelps MA, Hofmeister CC. G-CSF starting day +1 after autologous transplant is safer than day +5 or day +7 in patients with multiple myeloma. Blood 2016;128:5790.

    Article  Google Scholar 

  11. Faber E, Pytlik R, Slaby J, Zapletalova J, Kozak T, Raida L, et al. Individually determined dosing of filgrastim after autologous peripheral stem cell transplantation in patients with malignant lymphoma—results of a prospective multicentre controlled trial. Eur J Haematol. 2006;77:493–500.

    Article  CAS  Google Scholar 

  12. Singh AD, Parmar S, Patel K, et al. Granulocyte colony-stimulating factor use after autologous peripheral blood stem cell transplantation: comparison of two practices. Biol Blood Marrow Transplant. 2018;24:288–93.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Stem cell Transplant Program, University Hospitals of Cleveland Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA

    Naveed Ali, Brenda Cooper, Benjamin Tomlinson, Leland Metheny, Paolo Caimi, Kirsten Boughan, Molly Gallogly, Folashade Otegbeye, Ehsan Malek, Hillard Lazarus, Richard Creger & Marcos de Lima

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  1. Naveed Ali
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Correspondence to Marcos de Lima.

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Ali, N., Cooper, B., Tomlinson, B. et al. Treatment-related mortality following autologous hematopoietic stem cell transplantation is unaffected by timing of G-CSF administration. Bone Marrow Transplant 55, 1697–1700 (2020). https://doi.org/10.1038/s41409-020-0812-x

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