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Machine learning-based prediction of G-CSF-induced hematopoietic stem cell mobilization outcomes in healthy volunteers

Abstract

Haematopoietic stem cell transplantation (HSC-T) has been established as a fundamental therapeutic intervention for a wide range of hematological malignancies and disorders, with a proven record of efficacy spanning over five decades. Peripheral blood (PB) has become the haematopoietic stem cell (HSC) source of choice, surpassing bone marrow, owing to its cost-effectiveness, reduced invasiveness, higher cell yields, and shorter hospitalizations. Clinically, granulocyte-colony stimulating factor (G-CSF) administration is the standard procedure for inducing HSC mobilization. Nevertheless, a significant proportion of potential donors, ranging from 5% to 10%, exhibit suboptimal mobilization responses to G-CSF. To investigate this, we carried out a retrospective analysis of mobilization data from 1056 donors who underwent G-CSF-induced HSC mobilization over the 5-year period from 2018 to 2023. This comprehensive study elucidated the complex interplay between mobilization efficacy, as measured primarily by CD34+ cell yield, and a variety of influencing factors. Our data indicate that better mobilization outcomes are achieved in male donors than female donors. Additionally, we found a positive correlation between increased body weight and improved mobilization efficiency, implying a more favourable response to G-CSF in obese donors. Moreover, the implementation of a split-dose regimen for the mobilization agent significantly improved outcomes, highlighting the critical role of dosing strategies. Notably, younger donors exhibited better mobilization responses, underscoring age as a pivotal determinant of mobilization outcomes. Leveraging machine learning (ML) algorithms, we developed seven predictive models designed to forecast G-CSF-induced HSC mobilization outcomes on the basis of these variables.

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Fig. 1: Flow chart of donor selection for the prediction analysis.
Fig. 2: Scatter plots and bar charts of various baseline laboratory data from donors and their Day4 CD34+ cell counts.
Fig. 3: Feature selection and importance.
Fig. 4: Comparison of performance among different models.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

Code to reproduce models, analyses, and figures can be found at the following Github repository: https://github.com/CeShi232/ML-HSC.

References

  1. Saad A, de Lima M, Anand S, Bhatt VR, Bookout R, Chen G, et al. Hematopoietic Cell Transplantation, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2020;18:599–634. https://doi.org/10.6004/jnccn.2020.0021.

    Article  CAS  Google Scholar 

  2. Vo LT, Daley GQ. De novo generation of HSCs from somatic and pluripotent stem cell sources. Blood. 2015;125:2641–2648. https://doi.org/10.1182/blood-2014-10-570234.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL. Physiological migration of hematopoietic stem and progenitor cells. Science. 2001;294:1933–1936. https://doi.org/10.1126/science.1064081.

    Article  PubMed  CAS  Google Scholar 

  4. Richman CM, Weiner RS, Yankee RA. Increase in circulating stem cells following chemotherapy in man. Blood. 1976;47:1031–1039.

    Article  PubMed  CAS  Google Scholar 

  5. Henig I, Zuckerman T. Hematopoietic stem cell transplantation-50 years of evolution and future perspectives. Rambam Maimonides Med J. 2014;5(4):e0028 https://doi.org/10.5041/rmmj.10162.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Adra N, Abonour R, Althouse SK, Albany C, Hanna NH, Einhorn LH. High-dose chemotherapy and autologous peripheral-blood stem-cell transplantation for relapsed metastatic germ cell tumors: the Indiana University Experience. J Clin Oncol J Am Soc Clin Oncol. 2017;35:1096–1102. https://doi.org/10.1200/jco.2016.69.5395.

    Article  Google Scholar 

  7. Schmitz N, Linch DC, Dreger P, Goldstone AH, Boogaerts MA, Ferrant A, et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996;347:353–357. https://doi.org/10.1016/s0140-6736(96)90536-x.

    Article  PubMed  CAS  Google Scholar 

  8. Beyer J, Schwella N, Zingsem J, Strohscheer I, Schwaner I, Oettle H, et al. Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison. J Clin Oncol J Am Soc Clin Oncol. 1995;13:1328–1335. https://doi.org/10.1200/jco.1995.13.6.1328.

    Article  CAS  Google Scholar 

  9. To LB, Haylock DN, Kimber RJ, Juttner CA. High levels of circulating haemopoietic stem cells in very early remission from acute non-lymphoblastic leukaemia and their collection and cryopreservation. Br J Haematol. 1984;58:399–410. https://doi.org/10.1111/j.1365-2141.1984.tb03987.x.

    Article  PubMed  CAS  Google Scholar 

  10. Briddell RA, Hartley CA, Smith KA, McNiece IK. Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony-stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhanced repopulating potential. Blood. 1993;82:1720–1723.

    Article  PubMed  CAS  Google Scholar 

  11. Mayer P, Lam C, Obenaus H, Liehl E, Besemer J. Recombinant human GM-CSF induces leukocytosis and activates peripheral blood polymorphonuclear neutrophils in nonhuman primates. Blood. 1987;70:206–213.

    Article  PubMed  CAS  Google Scholar 

  12. Ramirez P, Rettig MP, Uy GL, Deych E, Holt MS, Ritchey JK, et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009;114:1340–1343. https://doi.org/10.1182/blood-2008-10-184721.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Zaldivar F, Eliakim A, Radom-Aizik S, Leu SY, Cooper DM. The effect of brief exercise on circulating CD34+ stem cells in early and late pubertal boys. Pediatr Res. 2007;61:491–495. https://doi.org/10.1203/pdr.0b013e3180332d36.

    Article  PubMed  Google Scholar 

  14. Juarez JG, Harun N, Thien M, Welschinger R, Baraz R, Pena AD, et al. Sphingosine-1-phosphate facilitates trafficking of hematopoietic stem cells and their mobilization by CXCR4 antagonists in mice. Blood. 2012;119:707–716. https://doi.org/10.1182/blood-2011-04-348904.

    Article  PubMed  CAS  Google Scholar 

  15. Cline MJ, Golde DW. Mobilization of hematopoietic stem cells (CFU-C) into the peripheral blood of man by endotoxin. Exp Hematol. 1977;5:186–190.

    PubMed  CAS  Google Scholar 

  16. Karpova D, Rettig MP, DiPersio JF. Mobilized peripheral blood: an updated perspective. F1000Research 2019;8, https://doi.org/10.12688/f1000research.21129.1

  17. Semerad CL, Christopher MJ, Liu F, Short B, Simmons PJ, Winkler I, et al. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood. 2005;106:3020–3027. https://doi.org/10.1182/blood-2004-01-0272.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Salvucci O, Jiang K, Gasperini P, Maric D, Zhu J, Sakakibara S, et al. MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1. Haematologica. 2012;97:818–826. https://doi.org/10.3324/haematol.2011.056945.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. To LB, Davy ML, Haylock DN, Dyson PG, Thorp D, Juttner CA. Autotransplantation using peripheral blood stem cells mobilized by cyclophosphamide. Bone Marrow Transplant. 1989;4:595–596.

    PubMed  CAS  Google Scholar 

  20. DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113:5720–5726. https://doi.org/10.1182/blood-2008-08-174946.

    Article  PubMed  CAS  Google Scholar 

  21. Greenbaum AM, Link DC. Mechanisms of G-CSF-mediated hematopoietic stem and progenitor mobilization. Leukemia. 2011;25:211–217. https://doi.org/10.1038/leu.2010.248.

    Article  PubMed  CAS  Google Scholar 

  22. To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. Blood. 2011;118:4530–4540. https://doi.org/10.1182/blood-2011-06-318220.

    Article  PubMed  CAS  Google Scholar 

  23. Bensinger W, Appelbaum F, Rowley S, Storb R, Sanders J, Lilleby K, et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol J Am Soc Clin Oncol. 1995;13:2547–2555. https://doi.org/10.1200/jco.1995.13.10.2547.

    Article  CAS  Google Scholar 

  24. Goterris R, Hernández-Boluda JC, Teruel A, Gómez C, Lis MJ, Terol MJ, et al. Impact of different strategies of second-line stem cell harvest on the outcome of autologous transplantation in poor peripheral blood stem cell mobilizers. Bone Marrow Transplant. 2005;36:847–853. https://doi.org/10.1038/sj.bmt.1705147.

    Article  PubMed  CAS  Google Scholar 

  25. Fiala MA, Park S, Slade M, DiPersio JF, Stockerl-Goldstein KE. Remobilization of hematopoietic stem cells in healthy donors for allogeneic transplantation. Transfusion. 2016;56:2331–2335. https://doi.org/10.1111/trf.13688.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25:44–56. https://doi.org/10.1038/s41591-018-0300-7.

    Article  PubMed  CAS  Google Scholar 

  27. Chen H, Liu J, Hua C, Feng J, Pang B, Cao D, et al. Accurate classification of white blood cells by coupling pre-trained ResNet and DenseNet with SCAM mechanism. BMC Bioinforma. 2022;23:282 https://doi.org/10.1186/s12859-022-04824-6.

    Article  Google Scholar 

  28. Arai Y, Kondo T, Fuse K, Shibasaki Y, Masuko M, Sugita J, et al. Using a machine learning algorithm to predict acute graft-versus-host disease following allogeneic transplantation. Blood Adv. 2019;3:3626–3634. https://doi.org/10.1182/bloodadvances.2019000934.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Xiang J, Shi M, Fiala MA, Gao F, Rettig MP, Uy GL, et al. Machine learning-based scoring models to predict hematopoietic stem cell mobilization in allogeneic donors. Blood Adv. 2022;6:1991–2000. https://doi.org/10.1182/bloodadvances.2021005149.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Farhadfar N, Hsu JW, Logan BR, Sees JA, Chitphakdithai P, Sugrue MW, et al. Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield. Blood Adv. 2020;4:706–716. https://doi.org/10.1182/bloodadvances.2019000923.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Lengefeld J, Cheng CW, Maretich P, Blair M, Hagen H, McReynolds MR, et al. Cell size is a determinant of stem cell potential during aging. Sci Adv. 2021;7:eabk0271 https://doi.org/10.1126/sciadv.abk0271.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132:631–644. https://doi.org/10.1016/j.cell.2008.01.025.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Pagliuca S, Kulasekararaj AG, Eikema DJ, Piepenbroek B, Iftikhar R, Satti TM, et al. Current use of androgens in bone marrow failure disorders: a report from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2024;109:765–776. https://doi.org/10.3324/haematol.2023.282935.

    Article  PubMed  CAS  Google Scholar 

  34. Bosi A, Barcellini W, Passamonti F, Fattizzo B. Androgen use in bone marrow failures and myeloid neoplasms: mechanisms of action and a systematic review of clinical data. Blood Rev. 2023;62:101132 https://doi.org/10.1016/j.blre.2023.101132.

    Article  PubMed  CAS  Google Scholar 

  35. Cheang C, Law S, Ren J, Chan W, Wang C, Dong Z. Prevalence of hyperuricemia in patients with severe obesity and the relationship between serum uric acid and severe obesity: A decade retrospective cross-section study in Chinese adults. Front public health. 2022;10:986954 https://doi.org/10.3389/fpubh.2022.986954.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tan MY, Mo CY, Li F, Zhao Q. The association between serum uric acid and hypertriglyceridemia: evidence from the National Health and Nutrition Examination Survey (2007-2018). Front Endocrinol. 2023;14:1215521 https://doi.org/10.3389/fendo.2023.1215521.

    Article  Google Scholar 

  37. Yano T, Katayama Y, Sunami K, Deguchi S, Nawa Y, Hiramatsu Y, et al. G-CSF-induced mobilization of peripheral blood stem cells for allografting: comparative study of daily single versus divided dose of G-CSF. Int J Hematol. 1997;66:169–178. https://doi.org/10.1016/s0925-5710(97)00590-2.

    Article  PubMed  CAS  Google Scholar 

  38. Kröger N, Renges H, Krüger W, Gutensohn K, Löliger C, Carrero I, et al. A randomized comparison of once versus twice daily recombinant human granulocyte colony-stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation. Br J Haematol. 2000;111:761–765.

    PubMed  Google Scholar 

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H.H. and Y.Z. conceived the study; C.S., X.Z., and Jimei Ge curated and analyzed the data; Y.Z. determined the methodology and acquired funding; C.S. wrote the original draft; and X.Z., Y.Q., Y.L., J.S., J.Y., X.L., Y.T., H.F., Y.Y., L.Y., and Y.W. reviewed and edited the manuscript.

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Correspondence to He Huang or Yanmin Zhao.

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Shi, C., Zeng, X., Ge, J. et al. Machine learning-based prediction of G-CSF-induced hematopoietic stem cell mobilization outcomes in healthy volunteers. Bone Marrow Transplant 60, 1316–1324 (2025). https://doi.org/10.1038/s41409-025-02666-3

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