The impact of iron metabolism disorders, transfusion load, and the use of erythropoiesis stimulants on quality of life, therapy tolerance and long-term survival of patients with chronic myeloid leukaemia after allogeneic stem cell transplantation cells

Authors

DOI:

https://doi.org/10.15587/2519-4798.2025.340317

Keywords:

хронічна мієлоїдна лейкемія, алогенна трансплантація стовбурових клітин, перевантаження залізом, феритин, магнітно-резонансна томографія печінки, деферазирокс, стимулятори еритропоезу, еритропоетин, якість життя, виживаність

Abstract

The aim. To analyze the impact of iron overload, transfusion burden, and the use of erythropoiesis-stimulating agents (ESAs) on quality of life, treatment tolerance, and long-term survival in patients with chronic myeloid leukaemia (CML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), summarize pathophysiological mechanisms and clinical consequences, and develop practical recommendations.

Materials and methods. Narrative review of current literature (2006–2025) with PubMed/PMC search and analysis of ELN, NCCN, ESMO guidelines, registry data, and prospective/retrospective studies on: the role of allogeneic HSCT in the era of tyrosine kinase inhibitors, the biology of iron overload (IO) and markers (ferritin, LIC by MRI), the efficacy of chelators (deferasirox) and EPO (recombinant erythropoietin), as well as post-transplant strategies (TKI support). The criteria for relevance were: CML populations or mixed cohorts after TGS with separate analysis of CML; the presence of “hard” endpoints (OS, PFS, DFS, relapse), quality of life and safety indicators.

Results. Allo-HSCT in CML is currently indicated mainly in cases of failure of ≥2 lines of ITC or in the acceleration/blast crisis phases; the prognosis depends significantly on the phase at the time of HSCT (the best indicators are in CP). PZ is formed through massive blood transfusions, cytolysis, and inflammation; ferritin is a convenient but inflammation-dependent marker, whereas LIC, as measured by MRI, more accurately reflects iron stores. Iron overload has immunomodulatory effects (decreased CD4/CD8, NK dysfunction, suppression of phagocytosis), which weaken the “graft-versus-leukaemia” effect, increasing the risk of relapse, invasive infections, and SOS syndrome. Hyperferritinemia before/after HSCT is associated with poorer survival, although part of the risk is due to concomitant systemic inflammation; combined measurement of ferritin and LIC/CRP improves prognostic accuracy. Deferasirox reduces ferritin and LIC and, in several studies, is associated with better OS/PFS due to a reduction in relapses; a possible mechanism is the “unblocking” of GVL (reduction of Tregs, preservation of NK), which is sometimes accompanied by a higher incidence of chronic PBRD. SEPs started after erythropoiesis recovery (≈day 28) accelerate Hb correction and reduce the need for transfusions; starting from scratch has no effect. The integrative model emphasizes interrelated loops: “TGS→anemia→transfusions→PZ→immunodysfunction→relapse/infections,” which can be modulated by chelation, timely administration of SEP, and risk-adapted TKI support.

Conclusions. Optimizing the results of allogeneic HSCT in CML requires systematic management of PV and anemia: 1) risk stratification taking into account the phase of CML, ferritin together with CRP and/or LIC; 2) consideration of deferasirox in persistent hyperferritinemia/high LIC with monitoring of renal function; 3) delayed start of SEP (around week 4) in the presence of inadequate endogenous response and iron availability; 4) Selective post-transplant TKI support. Large RCTs with “hard” endpoints are needed to distinguish between the contribution of iron and inflammation and to determine the optimal algorithms for chelation and erythropoietin therapy, taking into account the impact on QoL, relapses, and OS

Author Biography

Halyna Moroz, Shupyk National Healthcare University of Ukraine

PhD, Associate Professor

Department of Therapy, Family Medicine, Hematology and Transfusiology

References

  1. Cross, N. C. P., Ernst, T., Branford, S., Cayuela, J.-M., Deininger, M., Fabarius, A. et al. (2023). European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia. Leukemia, 37 (11), 2150–2167. https://doi.org/10.1038/s41375-023-02048-y
  2. Hochhaus, A., Baccarani, M., Silver, R. T., Schiffer, C., Apperley, J. F., Cervantes, F. et al. (2020). European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia, 34 (4), 966–984. https://doi.org/10.1038/s41375-020-0776-2
  3. Shah, N. P., Bhatia, R., Altman, J. K., Amaya, M., Begna, K. H., Berman, E. et al. (2024). Chronic Myeloid Leukemia, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network, 22 (1), 43–69. https://doi.org/10.6004/jnccn.2024.0007
  4. Jabbour, E., Kantarjian, H. (2025). Chronic Myeloid Leukemia. JAMA, 333 (18), 1618. https://doi.org/10.1001/jama.2025.0220
  5. Patra, P. C., Rainchwar, S., Singh, R., Bhatia, N., Bhatnagar, S., Palatty, R. J. et al. (2025). Allogeneic transplantation for CML blast phase: Learnings over last decade from a single centre in North India. Annals of Hematology, 104 (4), 2483–2493. https://doi.org/10.1007/s00277-025-06350-w
  6. Ju, H. Y., Choi, H. S., Park, H. J., Yoo, K. H., Lyu, C. J., Im, H. J. et al. (2025). Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric and Young Adult Patients with Chronic Myeloid Leukemia in Tyrosine Kinase Inhibitor Era: A Study of the Korean Blood and Marrow Transplantation Registry. Cancer Research and Treatment. https://doi.org/10.4143/crt.2024.1186
  7. Chalandon, Y., Simonetta, F., Masouridi-Levrat, S. (2025). How I approach hematopoietic stem cell transplantation for CML in a TKI world. Blood Journal. https://doi.org/10.1182/blood.2024026512
  8. Chalandon, Y., Sbianchi, G., Gras, L., Koster, L., Apperley, J., Byrne, J. et al. (2022). Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors: A retrospective study by the chronic malignancies working party of the EBMT. American Journal of Hematology, 98 (1), 112–121. https://doi.org/10.1002/ajh.26764
  9. Von dem Borne, P., Beaumont, F., Starrenburg, C., Oudshoorn, M., Hale, G., Falkenburg, J. et al. (2006). Outcomes after myeloablative unrelated donor stem cell transplantation using both in vitro and in vivo T-cell depletion with alemtuzumab. Haematologica, 91, 1559–1562.
  10. Atilla, E., Toprak, S. K., Demirer, T. (2017). Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation. Turkish Journal of Hematology, 34 (1), 1–9. https://doi.org/10.4274/tjh.2016.0450
  11. Pullarkat, V., Blanchard, S., Tegtmeier, B., Dagis, A., Patane, K., Ito, J., Forman, S. J. (2008). Iron overload adversely affects outcome of allogeneic hematopoietic cell transplantation. Bone Marrow Transplantation, 42 (12), 799–805. https://doi.org/10.1038/bmt.2008.262
  12. Adams, R. L. C., Bird, R. J. (2013). Safety and efficacy of deferasirox in the management of transfusion-dependent patients with myelodysplastic syndrome and aplastic anaemia: a perspective review. Therapeutic Advances in Hematology, 4 (2), 93–102. https://doi.org/10.1177/2040620712472355
  13. Vallejo, C., Batlle, M., Vazquez, L., Solano, C., Sampol, A., Duarte, R. et al. (2014). Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation. Haematologica, 99 (10), 1632–1637. https://doi.org/10.3324/haematol.2014.105908
  14. Cho, B., Jeon, Y., Hahn, A., Lee, T., Park, S., Yoon, J. et al. (2019). Improved survival outcomes and restoration of graft‐vs‐leukemia effect by deferasirox after allogeneic stem cell transplantation in acute myeloid leukemia. Cancer Medicine, 8 (2), 501–514. https://doi.org/10.1002/cam4.1928
  15. Jaspers, A., Baron, F., Willems, É., Seidel, L., Hafraoui, K., Vanstraelen, G. et al. (2014). Erythropoietin therapy after allogeneic hematopoietic cell transplantation: a prospective, randomized trial. Blood, 124 (1), 33–41. https://doi.org/10.1182/blood-2014-01-546333
  16. Pirotte, M., Fillet, M., Seidel, L., Jaspers, A., Baron, F., Beguin, Y. (2021). Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant. American Journal of Hematology, 96 (10), 1275–1286. https://doi.org/10.1002/ajh.26300
  17. Cserti-Gazdewich, C. (2018). Shifting ground and gaps in transfusion support of patients with hematological malignancies. Hematology, 2018 (1), 553–560. https://doi.org/10.1182/asheducation-2018.1.553
  18. Panch, S. R., Yau, Y. Y., West, K., Diggs, K., Sweigart, T., Leitman, S. F. (2014). Initial serum ferritin predicts number of therapeutic phlebotomies to iron depletion in secondary iron overload. Transfusion, 55 (3), 611–622. https://doi.org/10.1111/trf.12854
  19. Guan, X.-Z., Wang, L.-L., Pan, X., Liu, L., Sun, X.-L., Zhang, X.-J., Wang, D.-Q., Yu, Y. (2020). Clinical Indications of Recombinant Human Erythropoietin in a Single Center: A 10-Year Retrospective Study. Frontiers in Pharmacology, 11. https://doi.org/10.3389/fphar.2020.01110
  20. Sligar, C., Tomasiello, N. R., Cuthbertson, P., Nelson, T. L., Elhage, A., Sluyter, R., Watson, D. (2025). Use of Human Chronic Myeloid Leukemia Cells to Study Graft-Versus-Leukemia Immunity in a Xenogeneic Mouse Model of Graft-Versus-Host Disease. Graft-Versus-Host Disease, 2907, 333–358. https://doi.org/10.1007/978-1-0716-4430-0_16
The impact of iron metabolism disorders, transfusion load, and the use of erythropoiesis stimulants on quality of life, therapy tolerance and long-term survival of patients with chronic myeloid leukaemia after allogeneic stem cell transplantation cells

Downloads

Published

2025-10-03

How to Cite

Moroz, H. (2025). The impact of iron metabolism disorders, transfusion load, and the use of erythropoiesis stimulants on quality of life, therapy tolerance and long-term survival of patients with chronic myeloid leukaemia after allogeneic stem cell transplantation cells. ScienceRise: Medical Science, (2(63), 31–38. https://doi.org/10.15587/2519-4798.2025.340317

Issue

No. 2(63) (2025)

Section

Medical Science

License

Copyright (c) 2025 Halyna Moroz

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.

Authors, who are published in this journal, agree to the following conditions:

1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.

 2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.