Skip to main content

Advertisement

SpringerLink
Log in

Poor graft function after haploidentical stem cell transplantation with post-transplant cyclophosphamide

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

This is a retrospective cohort study of consecutive adult patients who received a haploidentical-SCT (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a single centre. Poor graft function (PGF) was defined as the occurrence of either persistent neutropenia (ANC < 0.5 × 109/µL) with poor response to granulocyte colony-stimulating factors (G-CSF) and/or thrombocytopenia (platelets < 20 × 109/L) with transfusion dependence, with complete donor chimerism and without concurrent severe GVHD or underlying disease relapse, during the first 12 months after transplantation. Forty-four (27.5%) out of 161 patients were diagnosed with PGF. Previous CMV reactivation was significantly more frequent in patients with PGF (88.6% versus 73.5%, p = 0.04) and the number of reactivations was also higher in these patients. Besides, early CMV reactivations in the first 6 months post-SCT were also significantly more frequent among patients with PGF (88.6% versus 71.8% p = 0.025). Thirty-two percent of patients with PGF were treated with increasing doses of thrombopoietin-receptor agonists (TRA) and 7 patients were treated with a donor CD34 + selected boost. In total, 93.2% of patients reached adequate peripheral blood counts in a median time of 101 days (range 11–475) after diagnosis. PGF is a frequent complication after haplo-SCT with PT-Cy. CMV reactivation might be the most relevant factor associated to its development. Even when most patients recover peripheral counts with support therapy, there is a group of patients with persistent cytopenias who can effectively be treated with TRA and/or a boost of CD34 + selective cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

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

References

  1. Thomas E, Storb R, Clift RA et al (1975) Bone-marrow transplantation (first of two parts). N Engl J Med 292(16):832–843. https://doi.org/10.1056/NEJM197504172921605

    Article  CAS  PubMed  Google Scholar 

  2. Luznik L, O’Donnell PV, Symons HJ et al (2008) HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 14(6):641–650. https://doi.org/10.1016/j.bbmt.2008.03.005

    Article  CAS  Google Scholar 

  3. Luznik L, O’Donnell PV, Fuchs EJ (2012) Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol 39(6):683–693. https://doi.org/10.1053/j.seminoncol.2012.09.005

    Article  CAS  PubMed  Google Scholar 

  4. Olsson R, Remberger M, Schaffer M et al (2013) Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transplant 48(4):537–543. https://doi.org/10.1038/bmt.2012.239

    Article  CAS  PubMed  Google Scholar 

  5. Mattsson J, Ringdén O, Storb R (2008) Graft failure after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 14(Suppl 1):165–170. https://doi.org/10.1016/j.bbmt.2007.10.025

    Article  Google Scholar 

  6. Remberger M, Mattsson J, Olsson R, Ringdén O (2011) Second allogeneic hematopoietic stem cell transplantation: a treatment for graft failure. Clin Transplant 25(1):E68-76. https://doi.org/10.1111/j.1399-0012.2010.01324.x

    Article  PubMed  Google Scholar 

  7. Zhao Y, Gao F, Shi J et al (2019) Incidence, risk factors, and outcomes of primary poor graft function after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 25(9):1898–1907. https://doi.org/10.1016/j.bbmt.2019.05.036

    Article  Google Scholar 

  8. Kong Y (2019) Poor graft function after allogeneic hematopoietic stem cell transplantation-an old complication with new insights☆. Semin Hematol 56(3):215–220. https://doi.org/10.1053/j.seminhematol.2018.08.004

    Article  PubMed  Google Scholar 

  9. Chen J, Wang H, Zhou J, Feng S (2020) Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation. Ther Adv Hematol 11:2040620720948743. https://doi.org/10.1177/2040620720948743

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sun YQ, Wang Y, Zhang XH et al (2019) Virus reactivation and low dose of CD34+ cell, rather than haploidentical transplantation, were associated with secondary poor graft function within the first 100 days after allogeneic stem cell transplantation. Ann Hematol 98(8):1877–1883. https://doi.org/10.1007/s00277-019-03715-w

    Article  CAS  PubMed  Google Scholar 

  11. Alchalby H, Yunus DR, Zabelina T, Ayuk F, Kröger N (2016) Incidence and risk factors of poor graft function after allogeneic stem cell transplantation for myelofibrosis. Bone Marrow Transplant 51(9):1223–1227. https://doi.org/10.1038/bmt.2016.98

    Article  CAS  PubMed  Google Scholar 

  12. Xiao Y, Song J, Jiang Z et al (2014) Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation. Int J Med Sci 11(6):652–657. https://doi.org/10.7150/ijms.6337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Buño I, Nava P, Simón A et al (2005) A comparison of fluorescent in situ hybridization and multiplex short tandem repeat polymerase chain reaction for quantifying chimerism after stem cell transplantation. Haematologica 90(10):1373–1379

    PubMed  Google Scholar 

  14. Ljungman P, de la Camara R, Cordonnier C et al (2008) Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant 42(4):227–240. https://doi.org/10.1038/bmt.2008.162

    Article  CAS  PubMed  Google Scholar 

  15. Sorror ML, Maris MB, Storb R et al (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106(8):2912–2919. https://doi.org/10.1182/blood-2005-05-2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Crocchiolo R, Ciceri F, Fleischhauer K et al (2009) HLA matching affects clinical outcome of adult patients undergoing haematopoietic SCT from unrelated donors: a study from the Gruppo Italiano Trapianto di Midollo Osseo and Italian Bone Marrow Donor Registry. Bone Marrow Transplant 44(9):571–577. https://doi.org/10.1038/bmt.2009.67

    Article  CAS  PubMed  Google Scholar 

  17. Reisner Y, Hagin D, Martelli MF (2011) Haploidentical hematopoietic transplantation: current status and future perspectives. Blood 118(23):6006–6017. https://doi.org/10.1182/blood-2011-07-338822

    Article  CAS  PubMed  Google Scholar 

  18. Shimomura Y, Hara M, Katoh D, Hashimoto H, Ishikawa T (2018) Enlarged spleen is associated with low neutrophil and platelet engraftment rates and poor survival after allogeneic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol 97(6):1049–1056. https://doi.org/10.1007/s00277-018-3278-9

    Article  PubMed  Google Scholar 

  19. Dominietto A, Raiola AM, van Lint MT et al (2001) Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol 112(1):219–227. https://doi.org/10.1046/j.1365-2141.2001.02468.x

    Article  CAS  PubMed  Google Scholar 

  20. Cho SY, Lee DG, Kim HJ (2019) Cytomegalovirus infections after hematopoietic stem cell transplantation: current status and future immunotherapy. Int J Mol Sci 20(11):E2666. https://doi.org/10.3390/ijms20112666

    Article  CAS  Google Scholar 

  21. Torok-Storb B, Boeckh M, Hoy C, Leisenring W, Myerson D, Gooley T (1997) Association of specific cytomegalovirus genotypes with death from myelosuppression after marrow transplantation. Blood 90(5):2097–2102

    Article  CAS  PubMed  Google Scholar 

  22. Marty FM, Ljungman P, Chemaly RF et al (2017) Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med 377(25):2433–2444. https://doi.org/10.1056/NEJMoa1706640

    Article  CAS  PubMed  Google Scholar 

  23. Isidori A, Borin L, Elli E et al (2018) Iron toxicity - its effect on the bone marrow. Blood Rev 32(6):473–479. https://doi.org/10.1016/j.blre.2018.04.004

    Article  CAS  PubMed  Google Scholar 

  24. Kwon M, Bailén R, Díez-Martín JL (2020) Evolution of the role of haploidentical stem cell transplantation: past, present, and future. Expert Rev Hematol 13(8):835–850. https://doi.org/10.1080/17474086.2020.1796621

    Article  CAS  PubMed  Google Scholar 

  25. Shono Y, Shiratori S, Kosugi-Kanaya M et al (2014) Bone marrow graft-versus-host disease: evaluation of its clinical impact on disrupted hematopoiesis after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 20(4):495–500. https://doi.org/10.1016/j.bbmt.2013.12.568

    Article  Google Scholar 

  26. Maruyama K, Aotsuka N, Kumano Y et al (2018) Immune-mediated hematopoietic failure after allogeneic hematopoietic stem cell transplantation: a common cause of late graft failure in patients with complete donor chimerism. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 24(1):43–49. https://doi.org/10.1016/j.bbmt.2017.08.018

    Article  CAS  Google Scholar 

  27. Bittencourt H, Rocha V, Filion A et al (2005) Granulocyte colony-stimulating factor for poor graft function after allogeneic stem cell transplantation: 3 days of G-CSF identifies long-term responders. Bone Marrow Transplant 36(5):431–435. https://doi.org/10.1038/sj.bmt.1705072

    Article  CAS  PubMed  Google Scholar 

  28. Marotta S, Marano L, Ricci P et al (2019) Eltrombopag for post-transplant cytopenias due to poor graft function. Bone Marrow Transplant 54(8):1346–1353. https://doi.org/10.1038/s41409-019-0442-3

    Article  CAS  PubMed  Google Scholar 

  29. Giammarco S, Sica S, Chiusolo P et al (2021) Eltrombopag for the treatment of poor graft function following allogeneic stem cell transplant: a retrospective multicenter study. Int J Hematol 114(2):228–234. https://doi.org/10.1007/s12185-021-03153-3

    Article  CAS  PubMed  Google Scholar 

  30. Stasia A, Ghiso A, Galaverna F et al (2014) CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 20(9):1440–1443. https://doi.org/10.1016/j.bbmt.2014.05.016

    Article  CAS  Google Scholar 

  31. Shahzad M, Siddiqui RS, Anwar I et al (2021) Outcomes with CD34-selected stem cell boost for poor graft function after allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. Transplant Cell Ther 27(10):877.e1-877.e8. https://doi.org/10.1016/j.jtct.2021.07.012

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the staff and nurses of all the hematology, transplant and ICU units for their care and contributions to making this work possible.

Funding

This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI17/01880 and PI2000521, co-financed by ERDF (FEDER) Funds from the European Commission. ‘A way of making Europe’, as well as grants from Asociación Madrileña de Hematología y Hemoterapia (AMHH) and Fundación Mutua Madrileña (FMM).

Author information

Author notes

  1. Ignacio Gómez-Centurión and Reyes Maria Martín Rojas contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007, Madrid, Spain

    Ignacio Gómez-Centurión, Reyes Maria Martin Rojas, Rebeca Bailén, Cristina Muñoz, Santiago Sabell, Gillen Oarbeascoa, Paula Fernández-Caldas, Diego Carbonell, Jorge Gayoso, Carolina Martínez-Laperche, Ismael Buño, Javier Anguita, José Luis Díez-Martin & Mi Kwon

  2. Gregorio Marañón Institute of Health Research, Madrid, Spain

    Ignacio Gómez-Centurión, Reyes Maria Martin Rojas, Rebeca Bailén, Cristina Muñoz, Santiago Sabell, Gillen Oarbeascoa, Paula Fernández-Caldas, Diego Carbonell, Jorge Gayoso, Carolina Martínez-Laperche, Ismael Buño, Javier Anguita, José Luis Díez-Martin & Mi Kwon

  3. Genomic Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Ismael Buño

Authors
  1. Ignacio Gómez-Centurión
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reyes Maria Martin Rojas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebeca Bailén
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristina Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Santiago Sabell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gillen Oarbeascoa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paula Fernández-Caldas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Diego Carbonell
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jorge Gayoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carolina Martínez-Laperche
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ismael Buño
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Javier Anguita
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. José Luis Díez-Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Mi Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: IGC, RMMR, MK.

Provision of study materials or patients: all authors.

Collection and assembly of data: IGC, RMMR, MK.

Data analysis and interpretation: all authors.

Manuscript writing: IGC, RMMR, MK.

Final approval of manuscript: all authors.

Corresponding author

Correspondence to Ignacio Gómez-Centurión.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the institutional review board and all patients gave written informed consent for us to collect their clinical information before transplantation or initiation of treatment for research purposes according to the local ethics policy and the Declaration of Helsinki.

Consent for publication

All patients provided written informed consent for publication.

Competing interests

The 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.

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

Gómez-Centurión, I., Martin Rojas, R.M., Bailén, R. et al. Poor graft function after haploidentical stem cell transplantation with post-transplant cyclophosphamide. Ann Hematol 102, 1561–1567 (2023). https://doi.org/10.1007/s00277-023-05206-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-023-05206-5

Keywords

Search

Navigation