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.

  • Article
  • Published:

Mobilization of hematopoietic stem cells using G-CSF with or without cyclophosphamide before autologous stem cell transplantation in patients with newly diagnosed multiple myeloma receiving induction therapy with or without daratumumab

Bone Marrow Transplantation (2025)Cite this article

Subjects

Access through your institution
Buy or subscribe

High dose melphalan combined with autologous stem cell transplantation (HDM/ASCT) remains the cornerstone of treatment in transplant-eligible newly diagnosed multiple myeloma patients (TE-NDMM) [1]. Mobilization of hematopoietic stem and progenitor cells (HSPCs) is achieved with granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide priming followed by G-CSF (C/G-CSF). In case of insufficient HSPC harvest, the CXCR4-antagonist plerixafor is used to increase HSPC yield [2]. The optimal HSPC mobilization method remains debated and depends on the induction treatment [3,4,5]. Dutch guidelines recommend a C/G-CSF mobilization regimen [6]. During the COVID-19 pandemic, G-CSF only was recommended by the European Hematology Association (EHA) and European Myeloma Network (EMN) to minimize hospital stays [7]. The addition of daratumumab to the induction regimen has improved the progression free survival of TE-NDMM and is now standard of care [1, 8]. However, several studies report lower apheresis yield in daratumumab-based regimens [9, 10]. This retrospective study compares HSPC mobilization in TE-NDMM using C/G-CSF vs. G-CSF only with various induction regimens, including daratumumab.

A retrospective analysis was conducted on TE-NDMM patients who underwent HSPC collection at the Erasmus Medical Centre in Rotterdam, the Netherlands (Supplementary Method). Out of 501 TE-NDMM patients, 52 were excluded mainly due to an alternative induction therapy (n = 24) and a different plasma cell malignancy (n = 19). Among the 378 single-transplant eligible patients, 199 received C/G-CSF and 179 received G-CSF only (Supplementary Fig. 2). Disease characteristics were evenly divided (Supplementary Table 1). Of these, 245 patients received non-daratumumab induction (VTd, VCd, or VRd), and 103 patients received daratumumab-based regimens (D-VTd, D-VRd, or D-Rd). Within the G-CSF only group, HSPC yields were significantly lower in daratumumab-treated patients (median after first apheresis 3.7 × 10^6 vs. 5.7 × 10^6, p < 0.0001; median total 3.7 × 10^6 vs. 5.8 × 10^6, p < 0.0001). In 245 patients receiving induction therapy without daratumumab (VTd, VCd and VRd), the success rate was similar between mobilization regimens (97% vs. 92%, p = 0.18). Plerixafor use was higher with G-CSF only (4% vs. 12%, p = 0.02). Despite a higher median HSPC yield with C/G-CSF, recovery rates were comparable (Supplementary Table 2). Of note, there was a change in 2021 in the minimum required CD34+ cells/kg following national guidelines [6], this could partly explain the difference in CD34+ cells collected between non-daratumumab and daratumumab treated patients, as most received daratumumab post-2021.

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

References

  1. Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2021;32:309–22.

    Article  PubMed  CAS  Google Scholar 

  2. DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin’s lymphoma. J Clin Oncol. 2009;27:4767–73.

    Article  PubMed  CAS  Google Scholar 

  3. Wang L, Xiang H, Yan Y, Deng Z, Li H, Li X, et al. Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis. Ann Hematol. 2021;100:563–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Chua CC, Lim HY, Chai KL, Ong J, Sim S, Wood C, et al. Peripheral blood stem cell mobilisation with G-CSF alone versus G-CSF and cyclophosphamide after bortezomib, cyclophosphamide and dexamethasone induction in multiple myeloma. Bone Marrow Transpl. 2018;53:1116–23.

    Article  CAS  Google Scholar 

  5. Silvennoinen R, Anttila P, Säily M, Lundan T, Heiskanen J, Siitonen TM, et al. A randomized phase II study of stem cell mobilization with cyclophosphamide+G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma. Bone Marrow Transpl. 2016;51:372–6.

    Article  CAS  Google Scholar 

  6. https://publicatie.hematologienederland.nl/richtlijnen/multipel-myeloom/. 2024.

  7. Terpos E, Engelhardt M, Cook G, Gay F, Mateos M-V, Ntanasis-Stathopoulos I, et al. Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN). Leukemia 2020;34:2000–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024;390:301–13.

    Article  PubMed  CAS  Google Scholar 

  9. Hulin C, Offner F, Moreau P, Roussel M, Belhadj K, Benboubker L, et al. Stem cell yield and transplantation in transplant-eligible newly diagnosed multiple myeloma patients receiving daratumumab + bortezomib/thalidomide/dexamethasone in the phase 3 CASSIOPEIA study. Haematologica 2021;106:2257–60.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chhabra S, Callander N, Watts NL, Costa LJ, Thapa B, Kaufman JL, et al. Stem Cell Mobilization Yields with Daratumumab- and Lenalidomide-Containing Quadruplet Induction Therapy in Newly Diagnosed Multiple Myeloma: Findings from the MASTER and GRIFFIN Trials. Transpl Cell Ther. 2023;29:174.e1–e10.

    Article  Google Scholar 

  11. Ma X, Wong SW, Zhou P, Chaulagain CP, Doshi P, Klein AK, et al. Daratumumab binds to mobilized CD34+ cells of myeloma patients in vitro without cytotoxicity or impaired progenitor cell growth. Exp Hematol Oncol. 2018;7:27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Dhakal B, Zhang MJ, Burns LJ, Tang X, Meyer C, Mau LW, et al. Efficacy, safety, and cost of mobilization strategies in multiple myeloma: a prospective, observational study. Haematologica 2023;108:2249–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Cathelijne Fokkema, Marjolein K. Appelman.

Authors and Affiliations

  1. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands

    Cathelijne Fokkema, Marjolein K. Appelman, Niels Veldhoen, Annie Spelt, Meriam Grootes, Ruth Wester, Emma de Pater, Annoek E. C. Broers, Pieter Sonneveld & Annemiek Broijl

  2. HOVON, Rotterdam, the Netherlands

    Bronno van der Holt

  3. Department of Hematology, HagaZiekenhuis, The Hague, the Netherlands

    Paula F. Ypma

Authors
  1. Cathelijne Fokkema
    View author publications

    Search author on:PubMed Google Scholar

  2. Marjolein K. Appelman
    View author publications

    Search author on:PubMed Google Scholar

  3. Niels Veldhoen
    View author publications

    Search author on:PubMed Google Scholar

  4. Annie Spelt
    View author publications

    Search author on:PubMed Google Scholar

  5. Bronno van der Holt
    View author publications

    Search author on:PubMed Google Scholar

  6. Meriam Grootes
    View author publications

    Search author on:PubMed Google Scholar

  7. Ruth Wester
    View author publications

    Search author on:PubMed Google Scholar

  8. Emma de Pater
    View author publications

    Search author on:PubMed Google Scholar

  9. Paula F. Ypma
    View author publications

    Search author on:PubMed Google Scholar

  10. Annoek E. C. Broers
    View author publications

    Search author on:PubMed Google Scholar

  11. Pieter Sonneveld
    View author publications

    Search author on:PubMed Google Scholar

  12. Annemiek Broijl
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Conceptualization, CF, BH, and AB; Methodology, CF, BH, and AB; Investigation, CF, MKA, NV, AS, and AB; Formal analysis, CF; Resources AS, MG, EP, RW, EP, and AB; Data curation, CF, MKA, and BH; Visualization, CF; Writing – Original Draft, C.F, M.K.A. and AB; Writing – Review & Editing, CF, MKA, NV, AS, BH, MG, RW, EP, PY, AECB, PS, and AB; Funding Acquisition, PS.; Supervision, AB, and PS; Project administration, AB.

Corresponding author

Correspondence to Annemiek Broijl.

Ethics declarations

Competing interests

BvdH has received honoraria for data safety monitoring board membership from Intergroupe Francophone du Myélome (IFM). RW receives honoraria from Sanofi and Janssen. PS receives honoraria and/or research funding from Amgen, Celgene, Janssen Pharmaceuticals, Karyopharm. AB receives honoraria from Amgen, Bristol-Myers Squibb, Celgene, and Janssen Pharmaceuticals. All other authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fokkema, C., Appelman, M.K., Veldhoen, N. et al. Mobilization of hematopoietic stem cells using G-CSF with or without cyclophosphamide before autologous stem cell transplantation in patients with newly diagnosed multiple myeloma receiving induction therapy with or without daratumumab. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02681-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41409-025-02681-4

Search

Advanced search

Quick links