Skip to main content
SpringerLink
Log in

Comparison of outcomes for patients with acute myeloid leukemia undergoing haploidentical stem cell transplantation in first and second complete remission

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

Abstract

There was no consensus on whether prognostic advantages existed when transplant conducted at first complete remission (CR1) stage than at second complete remission (CR2) stage for patients with AML who received haploidentical hematological stem cell transplantation (haplo-HSCT). In 768 consecutive AML patients who received haplo-HSCT from January 2014 to December 2017, a 1:2 ratio matched-pair analysis was performed, 69 patients who in CR2 group and 138 CR1 patients were enrolled. Hematopoietic recovery, graft versus host disease (GVHD), relapse, transplant related mortality (TRM), disease-free survival (DFS) and overall survival (OS) were compared in two groups, and further evaluated in low-, intermediate-, and high-risk subgroups. The cumulative incidences of 30-day myeloid recovery and 90-day platelet recovery were comparable in CR1 and CR2 groups. The cumulative incidences of grade II–IV and grade III–IV aGVHD were not significantly different. The cumulative incidences of relapse at 3-year and 5-year in these two groups were 12.4% versus 11.6% (P = 0.880) and 12.4% versus 17.5% (P = 0.322). The cumulative incidences of TRM at 3-year and 5-year were both 10.9% versus 23.2% (P = 0.019). The probability of DFS at 3-year and 5-year were 76.7% versus 65.2% (P = 0.029) and 76.7% versus 59.3% (P = 0.009). The probability of OS at 3-year and 5-year were 81.8% versus 68.1% (P = 0.026) and 76.7% versus 59.3% (P = 0.026). In the intermediate-risk group, TRM was lower in CR1 group, DFS and OS of CR1 group were superior to CR2 group. In conclusion, haplo-HSCT at CR1 stage was of better prognosis for intermediate-risk AML patients than at CR2 stage.

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
Fig. 5

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author.

Code availability

Not applicable.

References

  1. Xu L, Chen H, Chen J, Han M et al (2018) The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China-recommendations from the Chinese Society of Hematology. J Hematol Oncol 11:33. https://doi.org/10.1186/s13045-018-0564-x

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dohner H, Estey EH, Amadori S et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–474. https://doi.org/10.1182/blood-2009-07-235358

    Article  CAS  PubMed  Google Scholar 

  3. Koreth J, Schlenk R, Kopecky KJ et al (2009) Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 301:2349–2361. https://doi.org/10.1001/jama.2009.813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kuwatsuka Y, Miyamura K, Suzuki R et al (2009) Hematopoietic stem cell transplantation for core binding factor acute myeloid leukemia: t(8;21) and inv(16) represent different clinical outcomes. Blood 113:2096–2103. https://doi.org/10.1182/blood-2008-03-145862

    Article  CAS  PubMed  Google Scholar 

  5. Wang Y, Liu DH, Liu KY et al (2013) Impact of pretransplantation risk factors on post transplantation outcome of patients with acute myeloid leukemia in remission after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 19:283–290. https://doi.org/10.1016/j.bbmt.2012.10.002

    Article  PubMed  Google Scholar 

  6. D’Souza A, Fretham C, Lee SJ et al (2020) Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant 26:e177–e182. https://doi.org/10.1016/j.bbmt.2020.04.013

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gilleece MH, Labopin M, Savani BN et al (2020) Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT. Leukemia 34:87–99. https://doi.org/10.1038/s41375-019-0527-4

    Article  CAS  PubMed  Google Scholar 

  8. Dohner H, Estey E, Grimwade D et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447. https://doi.org/10.1182/blood-2016-08-733196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yan CH, Wang Y, Wang JZ et al (2016) Minimal residual disease- and graft-vs.-host disease-guided multiple consolidation chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant. J Hematol Oncol 9:87. https://doi.org/10.1186/s13045-016-0319-5

  10. Tsirigotis P, Byrne M, Schmid C et al (2016) Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transplant 51:1431–1438. https://doi.org/10.1038/bmt.2016.167

    Article  CAS  PubMed  Google Scholar 

  11. Yafour N, Beckerich F, Bulabois CE et al (2017) How to prevent relapse after allogeneic hematopoietic stem cell transplantation in patients with acute leukemia and myelodysplastic syndrome. Curr Res Transl Med 65:65–69. https://doi.org/10.1016/j.retram.2017.06.001

    Article  CAS  PubMed  Google Scholar 

  12. Zhao XS, Yan CH, Liu DH et al (2013) Combined use of WT1 and flow cytometry monitoring can promote sensitivity of predicting relapse after allogeneic HSCT without affecting specificity. Ann Hematol 92:1111–1119. https://doi.org/10.1007/s00277-013-1733-1

    Article  CAS  PubMed  Google Scholar 

  13. Lu DP, Dong L, Wu T et al (2006) Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 107:3065–3073. https://doi.org/10.1182/blood-2005-05-2146

    Article  CAS  PubMed  Google Scholar 

  14. Przepiorka D, Weisdorf D, Martin P et al (1995) 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 15:825–828

  15. Basara N, Schulze A, Wedding U et al (2009) Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission. Leukemia 23:635–640. https://doi.org/10.1038/leu.2008.352

    Article  CAS  PubMed  Google Scholar 

  16. Dohner H, Weisdorf DJ, Bloomfield CD (2015) Acute myeloid leukemia. N Engl J Med 373:1136–1152. https://doi.org/10.1056/NEJMra1406184

    Article  CAS  PubMed  Google Scholar 

  17. (2020) The 46(th) Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Poster Session (P001-P706). Bone Marrow Transplant 55:181–714. https://doi.org/10.1038/s41409-020-01120-w

  18. Michelis FV, Messner HA, Atenafu EG et al (2015) Patient age, remission status and HCT-CI in a combined score are prognostic for patients with AML undergoing allogeneic hematopoietic cell transplantation in CR1 and CR2. Bone Marrow Transplant 50:1405–1410. https://doi.org/10.1038/bmt.2015.165

    Article  CAS  PubMed  Google Scholar 

  19. Shimoni A, Labopin M, Savani B et al (2019) Comparable long-term outcome after allogeneic stem cell transplantation from sibling and matched unrelated donors in patients with acute myeloid leukemia older than 50 years: a report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 25:2251–2260. https://doi.org/10.1016/j.bbmt.2019.06.031

    Article  PubMed  Google Scholar 

  20. Jentzsch M, Bischof L, Backhaus D et al (2022) Impact of MRD status in patients with AML undergoing allogeneic stem cell transplantation in the first vs the second remission. Blood Adv 6:4570–4580. https://doi.org/10.1182/bloodadvances.2022007168

  21. Chang YJ, Luznik L, Fuchs EJ, Huang XJ (2016) How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation? J Hematol Oncol 9:35. https://doi.org/10.1186/s13045-016-0265-2

  22. Wang Y, Chang YJ, Xu LP 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 

  23. Wang Y, Wu DP, Liu QF et al (2018) Donor and recipient age, gender and ABO incompatibility regardless of donor source: validated criteria for donor selection for haematopoietic transplants. Leukemia 32:492–498. https://doi.org/10.1038/leu.2017.199

    Article  CAS  PubMed  Google Scholar 

  24. Wang Y, Liu QF, Xu LP et al (2016) Haploidentical versus matched-sibling transplant in adults with Philadelphia-negative high-risk acute lymphoblastic leukemia: a biologically phase III randomized study. Clin Cancer Res 22:3467–3476. https://doi.org/10.1158/1078-0432.CCR-15-2335

    Article  CAS  PubMed  Google Scholar 

  25. Wang Y, Chen H, Chen J et al (2018) The consensus on the monitoring, treatment, and prevention of leukemia relapse after allogeneic hematopoietic stem cell transplantation in China. Cancer Lett 438:63–75. https://doi.org/10.1016/j.canlet.2018.08.030

    Article  CAS  PubMed  Google Scholar 

  26. Chang YJ, Wang Y, Liu YR et al (2017) Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis. J Hematol Oncol 10:134. https://doi.org/10.1186/s13045-017-0502-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang Y, Liu DH, Liu KY et al (2013) Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer 119:978–985. https://doi.org/10.1002/cncr.27761

    Article  PubMed  Google Scholar 

  28. Cornelissen JJ, Gratwohl A, Schlenk RF et al (2012) The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 9:579–590. https://doi.org/10.1038/nrclinonc.2012.150

    Article  CAS  PubMed  Google Scholar 

  29. Short NJ, Zhou S, Fu C, Berry DA et al (2020) Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol 6:1890–1899. https://doi.org/10.1001/jamaoncol.2020.4600

    Article  PubMed  PubMed Central  Google Scholar 

  30. Murdock HM, Kim HT, Denlinger N et al (2022) Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML. Blood 139:3546–3557. https://doi.org/10.1182/blood.2021014520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cornelissen JJ, van Putten WL, Verdonck LF et al (2007) Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood 109:3658–3666. https://doi.org/10.1182/blood-2006-06-025627

    Article  CAS  PubMed  Google Scholar 

  32. Halaburda K, Labopin M, Mailhol A et al (2020) Allogeneic stem cell transplantation in second complete remission for core binding factor acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica 105:1723–1730. https://doi.org/10.3324/haematol.2019.222810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (82270227&82070189), National Key Research and Development Program (2022YFA1103300 & 2019YFC0840606 & 2021YFA1100904), Major Program of the National Natural Science Foundation of China (No. 82293630), Key Program of the National Natural Science Foundation of China (No. 81930004), Peking University People’s Hospital Research and Development Funds (RDL2022-13).

Author information

Author notes

  1. Wen-Jing Yu and Yu-qian Sun contributed equally to this work.

Authors and Affiliations

  1. Peking University People’s Hospital, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Wen-Jing Yu, Yu-qian Sun, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang & Yu Wang

  2. Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China

    Xiao-Jun Huang

  3. Collaborative Innovation Center of Hematology China, Peking University, Beijing, 100871, China

    Xiao-Jun Huang & Yu Wang

Authors
  1. Wen-Jing Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-qian Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lan-Ping Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kai-Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao-Jun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design of study: Wen-Jing Yu, Yu Wang; collection and assembly of data: Wen-Jing Yu, Yu-qian Sun; data analysis and interpretation: Wen-Jing Yu, Yu-qian Sun, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang, Yu Wang; manuscript writing: Wen-Jing Yu, Yu-qian Sun, Yu Wang; critical review: Wen-Jing Yu, Yu-qian Sun, Lan-Ping Xu, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang, Yu Wang.

Corresponding author

Correspondence to Yu Wang.

Ethics declarations

Ethics approval

This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the ethics committee of the institution.

Consent to participate

Informed consent was obtained from all patients for being included in the study.

Consent for publication

All patients provided written informed consent at data registration for publication purpose.

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.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 18 KB)

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

Yu, WJ., Sun, Yq., Xu, LP. et al. Comparison of outcomes for patients with acute myeloid leukemia undergoing haploidentical stem cell transplantation in first and second complete remission. Ann Hematol 102, 2241–2250 (2023). https://doi.org/10.1007/s00277-023-05324-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-023-05324-0

Keywords

Search

Navigation