Skip to main content

Advertisement

SpringerLink
Log in

Risk factors for adverse outcomes following haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide: a two-center analysis

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

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for several malignant hematologic diseases and alternative donors, including haploidentical, play a significant role in HCT. Despite the increasing use of haplo-HCT with PTCy, some questions remain open. The objective of the present study was to investigate risk factors for adverse outcomes after haplo-HCT with PTCy. This is a retrospective study conducted at two Brazilian centers. A total of 103 patients with hematologic malignancies who underwent first allogeneic, haploidentical HCT with PTCy were included. Risk factors for death were age at transplant (HR = 1.03 for each year; p = 0.002) and high/very high disease risk index (DRI; HR = 2.77; p = 0.0007) and mother as the donor compared with other donors (HR = 3.53; p = 0.005). In multivariate analysis, PFS was significantly poorer for older patients (HR = 1.02; p = 0.006), high/very high DRI (HR = 2.39; p = 0.003), and mother as the donor compared with other donors (HR = 3.18; p = 0.006). Relapse rate was higher for high/very high DRI (HR = 4.01; p = 0.002) and mother as the donor compared with other donors (HR = 2.52; p = 0.05). NRM was higher for older patients (HR = 1.03 for each year; p = 0.03). Tacrolimus was a protective factor for grades II–IV aGVHD (HR = 0.46; p = 0.04) compared with cyclosporine. Peripheral blood (PBSC) was a risk factor for cGVHD (HR = 3.48; p = 0.006), while tacrolimus was protective (HR = 0.30; p = 0.009). Mother as the donor compared with other donors was also a risk factor for poorer OS, PFS, and relapse, suggesting that this combination should be avoided. Tacrolimus was protective for both grades II–IV aGVHD and cGVHD, suggesting that tacrolimus may be more effective than cyclosporine in preventing GVHD. PBSC was a risk factor for cGVHD without any impact on relapse. Prospective studies comparing tacrolimus with cyclosporine are awaited.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Raiola AM, Dominietto A, di Grazia C et al (2014) Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant 20:1573–1579. https://doi.org/10.1016/j.bbmt.2014.05.029

    Article  PubMed  Google Scholar 

  2. O’Reilly RJ, Keever C, Kernan NA et al (1987) HLA nonidentical T cell depleted marrow transplants: a comparison of results in patients treated for leukemia and severe combined immunodeficiency disease. Transplant Proc 19:55–60

    PubMed  Google Scholar 

  3. Aversa F, Tabilio A, Terenzi A et al (1994) Successful engraftment of T-cell-depleted haploidentical “three-loci” incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood 84:3948–3955

    Article  CAS  Google Scholar 

  4. Bethge WA, Faul C, Bornhäuser M et al (2008) Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: an update. Blood Cells Mol Dis 40:13–19. https://doi.org/10.1016/j.bcmd.2007.07.001

    Article  CAS  PubMed  Google Scholar 

  5. Rizzieri DA, Koh LP, Long GD et al (2007) Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol 25:690–697. https://doi.org/10.1200/JCO.2006.07.0953

    Article  CAS  PubMed  Google Scholar 

  6. 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 14:641–650. https://doi.org/10.1016/j.bbmt.2008.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Arcuri LJ, Hamerschlak N, Rocha V et al (2021) Outcomes after haploidentical hematopoietic cell transplantation with post-transplantation cyclophosphamide: a systematic review and meta-analysis comparing myeloablative with reduced-intensity conditioning regimens and bone marrow with peripheral blood stem cell grafts. Transplant Cell Ther S2666636721009969. https://doi.org/10.1016/j.jtct.2021.06.011

  8. Wang Y, Chang Y-J, Xu L-P et al (2014) Who is the best donor for a related HLA haplotype-mismatched transplant? Blood 124:843–850. https://doi.org/10.1182/blood-2014-03-563130

    Article  CAS  PubMed  Google Scholar 

  9. Fuchs EJ (2012) Haploidentical transplantation for hematologic malignancies: where do we stand? Hematology Am Soc Hematol Educ Program 2012:230–236. https://doi.org/10.1182/asheducation-2012.1.230

    Article  PubMed  Google Scholar 

  10. Ciurea SO, Al Malki MM, Kongtim P et al (2019) The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation. Bone Marrow Transplant. https://doi.org/10.1038/s41409-019-0499-z

    Article  PubMed  Google Scholar 

  11. Huselton E, Slade M, Trinkaus KM et al (2018) Propensity score analysis of conditioning intensity in peripheral blood haploidentical hematopoietic cell transplantation. Biol Blood Marrow Transplant 24:2047–2055. https://doi.org/10.1016/j.bbmt.2018.05.024

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bashey A, Zhang M-J, McCurdy SR et al (2017) Mobilized peripheral blood stem cells versus unstimulated bone marrow as a graft source for T-cell-replete haploidentical donor transplantation using post-transplant cyclophosphamide. J Clin Oncol 35:3002–3009. https://doi.org/10.1200/JCO.2017.72.8428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Armand P, Gibson CJ, Cutler C et al (2012) A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 120:905–913. https://doi.org/10.1182/blood-2012-03-418202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Harris AC, Young R, Devine S et al (2016) International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant 22:4–10. https://doi.org/10.1016/j.bbmt.2015.09.001

    Article  PubMed  Google Scholar 

  15. Jagasia MH, Greinix HT, Arora M et al (2015) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 21:389-401.e1. https://doi.org/10.1016/j.bbmt.2014.12.001

    Article  PubMed  Google Scholar 

  16. Solomon SR, Aubrey MT, Zhang X et al (2018) Selecting the best donor for haploidentical transplant: impact of HLA, killer cell immunoglobulin-like receptor genotyping, and other clinical variables. Biol Blood Marrow Transplant 24:789–798. https://doi.org/10.1016/j.bbmt.2018.01.013

    Article  CAS  PubMed  Google Scholar 

  17. DeZern AE, Franklin C, Tsai H-L et al (2021) Relationship of donor age and relationship to outcomes of haploidentical transplantation with posttransplant cyclophosphamide. Blood Adv 5:1360–1368. https://doi.org/10.1182/bloodadvances.2020003922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. McCurdy SR, Zhang M-J, St Martin A et al (2018) Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide. Blood Adv 2:299–307. https://doi.org/10.1182/bloodadvances.2017014829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang Y, Liu Q-F, Lin R et al (2021) Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation: long-term follow-up of a multicenter, randomized controlled trial. Science Bulletin 66:2498–2505. https://doi.org/10.1016/j.scib.2021.06.002

    Article  CAS  Google Scholar 

  20. Stern M, Ruggeri L, Mancusi A et al (2008) Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood 112:2990–2995. https://doi.org/10.1182/blood-2008-01-135285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ruggeri A, Labopin M, Bacigalupo A et al (2018) Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide. Cancer 124:1428–1437. https://doi.org/10.1002/cncr.31228

    Article  CAS  PubMed  Google Scholar 

  22. Cutler C, Giri S, Jeyapalan S et al (2001) Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol 19:3685–3691. https://doi.org/10.1200/JCO.2001.19.16.3685

    Article  CAS  PubMed  Google Scholar 

  23. Eapen M, Logan BR, Confer DL et al (2007) Peripheral blood grafts from unrelated donors are associated with increased acute and chronic graft-versus-host disease without improved survival. Biol Blood Marrow Transplant 13:1461–1468. https://doi.org/10.1016/j.bbmt.2007.08.006

    Article  PubMed  PubMed Central  Google Scholar 

  24. Körbling M, Anderlini P (2001) Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood 98:2900–2908. https://doi.org/10.1182/blood.v98.10.2900

    Article  PubMed  Google Scholar 

  25. Flowers MED, Inamoto Y, Carpenter PA et al (2011) Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood 117:3214–3219. https://doi.org/10.1182/blood-2010-08-302109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hahn T, McCarthy PL, Zhang M-J et al (2008) Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol 26:5728–5734. https://doi.org/10.1200/JCO.2008.17.6545

    Article  PubMed  PubMed Central  Google Scholar 

  27. Flowers MED, Parker PM, Johnston LJ et al (2002) Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 100:415–419. https://doi.org/10.1182/blood-2002-01-0011

    Article  CAS  PubMed  Google Scholar 

  28. Chiusolo P, Bug G, Olivieri A et al (2018) A modified post-transplant cyclophosphamide regimen, for unmanipulated haploidentical marrow transplantation, in acute myeloid leukemia: a multicenter study. Biol Blood Marrow Transplant 24:1243–1249. https://doi.org/10.1016/j.bbmt.2018.01.031

    Article  CAS  PubMed  Google Scholar 

  29. Castagna L, Bramanti S, Furst S et al (2016) Tacrolimus compared with cyclosporine A after haploidentical T-cell replete transplantation with post-infusion cyclophosphamide. Bone Marrow Transplant 51:462–465. https://doi.org/10.1038/bmt.2015.289

    Article  CAS  PubMed  Google Scholar 

  30. Inamoto Y, Flowers MED, Appelbaum FR et al (2011) A retrospective comparison of tacrolimus versus cyclosporine with methotrexate for immunosuppression after allogeneic hematopoietic cell transplantation with mobilized blood cells. Biol Blood Marrow Transplant 17:1088–1092. https://doi.org/10.1016/j.bbmt.2011.01.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kanda Y, Kobayashi T, Mori T et al (2016) A randomized controlled trial of cyclosporine and tacrolimus with strict control of blood concentrations after unrelated bone marrow transplantation. Bone Marrow Transplant 51:103–109. https://doi.org/10.1038/bmt.2015.222

    Article  CAS  PubMed  Google Scholar 

  32. Nash RA, Antin JH, Karanes C et al (2000) Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 96:2062–2068

    CAS  PubMed  Google Scholar 

  33. Ratanatharathorn V, Nash RA, Przepiorka D et al (1998) Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 92:2303–2314

    CAS  PubMed  Google Scholar 

  34. Hiraoka A, Ohashi Y, Okamoto S et al (2001) Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation. Bone Marrow Transplant 28:181–185. https://doi.org/10.1038/sj.bmt.1703097

    Article  CAS  PubMed  Google Scholar 

  35. McCurdy SR, Kanakry JA, Showel MM et al (2015) Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood 125:3024–3031. https://doi.org/10.1182/blood-2015-01-623991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ciurea SO, Rodrigues M, Giralt S, de Lima M (2009) Aging, acute myelogenous leukemia, and allogeneic transplantation: do they belong in the same sentence? Clin Lymphoma Myeloma 9:289–297. https://doi.org/10.3816/CLM.2009.n.057

    Article  CAS  PubMed  Google Scholar 

  37. Gratwohl A (2012) The EBMT risk score. Bone Marrow Transplant 47:749–756. https://doi.org/10.1038/bmt.2011.110

    Article  CAS  PubMed  Google Scholar 

  38. Ciurea SO, Shah MV, Saliba RM et al (2018) Haploidentical transplantation for older patients with acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant 24:1232–1236. https://doi.org/10.1016/j.bbmt.2017.09.005

    Article  PubMed  Google Scholar 

  39. Souza MA, Passos AM, Treitinger A, Spada C (2010) Seroprevalence of cytomegalovirus antibodies in blood donors in southern, Brazil. Rev Soc Bras Med Trop 43:359–361

    Article  Google Scholar 

  40. Solomon SR, Solh M, Morris LE et al (2016) Myeloablative conditioning with PBSC grafts for T cell-replete haploidentical donor transplantation using posttransplant cyclophosphamide. Adv Hematol 2016:9736564. https://doi.org/10.1155/2016/9736564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Viviane de Jesus Torres Lima and Anderson Felipe da Silva contributed equally to this work.

Authors and Affiliations

  1. Bone Marrow Transplantation Department, Hospital Israelita Albert Einstein, Guaramomis 480/64, São Paulo, SP, CEP 04076-010, Brazil

    Viviane Jesus Torres de Lima, Anderson Felipe da Silva, Lucila Nassif Kerbauy, Mariana Nassif Kerbauy, Andreza Alice Feitosa Ribeiro, Cinthya Feitosa da Silva, Nelson Hamerschlak & Leonardo Javier Arcuri

  2. Bone Marrow Transplantation Department, Instituto Nacional de Cancer, Rio de Janeiro, Brazil

    Decio Lerner, Marta Colares & Leonardo Javier Arcuri

  3. Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil

    Leonardo Javier Arcuri

Authors
  1. Viviane Jesus Torres de Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anderson Felipe da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucila Nassif Kerbauy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mariana Nassif Kerbauy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Decio Lerner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marta Colares
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andreza Alice Feitosa Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cinthya Feitosa da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nelson Hamerschlak
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Leonardo Javier Arcuri
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VJTL, AFS, LNK, MNK, AAFR, CCS, NH, and LJA were responsible for the study design and local conduction of the study. DL and MC were responsible for local conduction of the study. VJTL, CCS, and LJA collected the data. VJTL, LNK, NH, and LJA wrote and critically reviewed the manuscript.

Corresponding author

Correspondence to Leonardo Javier Arcuri.

Ethics declarations

Consent to participate

Ethics committee waived informed consent.

Conflict of interest

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.

The authors declare that the manuscript is original and has not been published before.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Lima, V.J.T., da Silva, A.F., Kerbauy, L.N. et al. Risk factors for adverse outcomes following haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide: a two-center analysis. Ann Hematol 101, 1795–1802 (2022). https://doi.org/10.1007/s00277-022-04865-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-022-04865-0

Keywords

Search

Navigation