Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Comparative analysis of Decitabine intensified BUCY2 and BUCY2 conditioning regimen for high-risk MDS patients undergoing allogeneic hematopoietic stem cell transplantation

Abstract

The optimal conditioning regimen for high-risk myelodysplastic syndrome (MDS) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. This study aimed to explore the anti-leukemic efficacy and toxicity of Decitabine (Dec, 20 mg/m2/day, day −11 to −7) intensified BUCY2 vs. traditional regimen in high-risk MDS population. We retrospectively evaluated 93 consecutive high-risk MDS patients undergoing allo-HSCT in our institution, comparing discrepancies in clinical characteristics and outcomes between cases using Dec-intensified BUCY2 (n = 52) and traditional BUCY2 regimen (n = 41). Three-year cumulative incidence of relapse after Dec-intensified BUCY2 conditioning was remarkably lower than that of patients using BUCY2 regimen (20.2% vs. 39.0%, p = 0.034). Overall survival and disease-free survival at 3 years for Dec-intensified BUCY2 group were 70.2% and 64.9%, respectively, which were significantly improved when compared with BUCY2 group (51.1% and 43.9%, p = 0.031 and p = 0.027). Furthermore, overall survival and disease-free survival for MDS cases receiving cytoreduction therapy were dramatically better than patients in non-cytoreduction group (p = 0.041, p = 0.047). In summary, the Dec-intensified conditioning regimen could be effective and feasible, providing prominent recurrence control with moderate toxicity for high-risk MDS patients. These patients might also benefit from pre-transplant cytoreductive therapeutic schedules. Larger randomized controlled trials are still needed to further confirm these conclusions.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Cumulative incidences of GVHD post-transplant for high-risk MDS patients following Decitabine intensified BUCY2 and BUCY2 preparative regimens.
Fig. 2: The influences of conditioning regimens on post-transplant outcomes of high-risk MDS patients.
Fig. 3: The impacts of cytoreductive therapy on post-transplant outcomes of high-risk MDS patients.

Data availability

All data generated or analyzed during this study are included in this article.

References

  1. Yoo JW, Im HJ, Kim H, Koh KN, Kang SH, Min SY, et al. Improved outcomes of allogeneic hematopoietic stem cell transplantation including haploidentical transplantation for childhood myelodysplastic syndrome. Bone Marrow Transpl. 2020;55:1595–603.

    CAS  Article  Google Scholar 

  2. Warlick ED, Cioc A, Defor T, Dolan M, Weisdorf D. Allogeneic stem cell transplantation for adults with myelodysplastic syndromes: importance of pretransplant disease burden. Biol Blood Marrow Transpl. 2009;15:30–8.

    Article  Google Scholar 

  3. Yahng SA, Kim M, Kim TM, Jeon YW, Yoon JH, Shin SH, et al. Better transplant outcome with pre-transplant marrow response after hypomethylating treatment in higher-risk MDS with excess blasts. Oncotarget. 2017;8:12342–54.

    Article  Google Scholar 

  4. Della Porta MG, Jackson CH, Alessandrino EP, Rossi M, Bacigalupo A, van Lint MT, et al. Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System. Leukemia. 2017;31:2449–57.

    Article  Google Scholar 

  5. Schuler E, Boughoufala S, Rautenberg C, Nachtkamp K, Dienst A, Fenk R, et al. Relapse patterns and treatment strategies in patients receiving allogeneic hematopoietic stem cell transplantation for myeloid malignancies. Ann Hematol. 2019;98:1225–35.

    CAS  Article  Google Scholar 

  6. Schroeder T, Rachlis E, Bug G, Stelljes M, Klein S, Steckel NK, et al. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions-a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transpl. 2015;21:653–60.

    CAS  Article  Google Scholar 

  7. Zhang R, Lu X, Wang H, You Y, Zhong Z, Zang S, et al. Idarubicin-intensified hematopoietic cell transplantation improves relapse and survival of high-risk acute leukemia patients with minimal residual disease. Biol Blood Marrow Transpl. 2019;25:47–55.

    CAS  Article  Google Scholar 

  8. Zhang R, Shi W, Wang HF, You Y, Zhong ZD, Li WM, et al. Idarubicin-intensified haploidentical HSCT with GvHD prophylaxis of ATG and basiliximab provides comparable results to sibling donors in high-risk acute leukemia. Bone Marrow Transpl. 2017;52:1253–60.

    CAS  Article  Google Scholar 

  9. Fang J, Zhang R, Wang H, Hong M, Wu Q, Nie D, et al. Idarubicin-intensified BUCY2 conditioning regimen improved survival in high-risk acute myeloid, but not lymphocytic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective comparative study. Leuk Res. 2016;46:61–8.

    CAS  Article  Google Scholar 

  10. Wu Q, Zhang R, Wang H, You Y, Zhong Z, Hong M, et al. Comparison of outcomes of idarubicin intensified TBI-CY and traditional TBI-CY conditioning regimen for high-risk acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation: A single center experience. Leuk Res. 2015;39:1192–200.

    CAS  Article  Google Scholar 

  11. Ogawa S. Genetics of MDS. Blood. 2019;133:1049–59.

    CAS  Article  Google Scholar 

  12. Stosch JM, Heumüller A, Niemöller C, Bleul S, Rothenberg-Thurley M, Riba J, et al. Gene mutations and clonal architecture in myelodysplastic syndromes and changes upon progression to acute myeloid leukaemia and under treatment. Br J Haematol. 2018;182:830–42.

    CAS  Article  Google Scholar 

  13. Zhou X, Mei C, Zhang J, Lu Y, Lan J, Lin S, et al. Epigenetic priming with decitabine followed by low dose idarubicin and cytarabine in acute myeloid leukemia evolving from myelodysplastic syndromes and higher-risk myelodysplastic syndromes: a prospective multicenter single-arm trial. Hematol Oncol. 2020;38:531–40.

    CAS  Article  Google Scholar 

  14. Odenike O, Onida F, Padron E. Myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms: an update on risk stratification, molecular genetics, and therapeutic approaches including allogeneic hematopoietic stem cell transplantation. Am Soc Clin Oncol Educ Book. 2015;35:e398–412.

    Article  Google Scholar 

  15. Wang QY, Li Y, Liang ZY, Yin Y, Liu W, Wang Q, et al. Decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with intermediate- and high-risk myelodysplastic syndrome/acute myeloid leukemia: potential decrease in the incidence of acute graft versus host disease. Cancer Manag Res. 2019;11:10195–203.

    CAS  Article  Google Scholar 

  16. Alessandrino EP, Della Porta MG, Pascutto C, Bacigalupo A, Rambaldi A. Should cytoreductive treatment be performed before transplantation in patients with high-risk myelodysplastic syndrome? J Clin Oncol. 2013;31:2761–2.

    Article  Google Scholar 

  17. Damaj G, Mohty M, Robin M, Michallet M, Chevallier P, Beguin Y, et al. Upfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative conditioning for patients with myelodysplastic syndrome: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire. Biol Blood Marrow Transpl. 2014;20:1349–55.

    Article  Google Scholar 

  18. Damaj G, Duhamel A, Robin M, Beguin Y, Michallet M, Mohty M, et al. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies. J Clin Oncol. 2012;30:4533–40.

    CAS  Article  Google Scholar 

  19. Gerds AT, Gooley TA, Estey EH, Appelbaum FR, Deeg HJ, Scott BL. Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS. Biol Blood Marrow Transpl. 2012;18:1211–8.

    CAS  Article  Google Scholar 

  20. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

    CAS  Article  Google Scholar 

  21. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–65.

    CAS  Article  Google Scholar 

  22. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419–25.

    CAS  Article  Google Scholar 

  23. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  Google Scholar 

  24. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. 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 Transpl. 2015;21:389–401.

    Article  Google Scholar 

  25. Guièze R, Damaj G, Pereira B, Robin M, Chevallier P, Michallet M, et al. Management of myelodysplastic syndrome relapsing after allogeneic hematopoietic stem cell transplantation: a study by the French Society of Bone Marrow Transplantation and Cell Therapies. Biol Blood Marrow Transpl. 2016;22:240–7.

    Article  Google Scholar 

  26. Wu D, Du X, Jin J, Xiao Z, Shen Z, Shao Z, et al. Decitabine for treatment of myelodysplastic syndromes in Chinese patients: an open-label, phase-3b study. Adv Ther. 2015;32:1140–59.

    Article  Google Scholar 

  27. Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375:2023–36.

    CAS  Article  Google Scholar 

  28. Sidaway P. Haematological cancer: TP53 mutations sensitize to decitabine. Nat Rev Clin Oncol. 2017;14:72.

    CAS  Article  Google Scholar 

  29. Chang CK, Zhao YS, Xu F, Guo J, Zhang Z, He Q, et al. TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes. Br J Haematol. 2017;176:600–8.

    CAS  Article  Google Scholar 

  30. Flotho C, Sommer S, Lübbert M. DNA-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia. Semin Cancer Biol. 2018;51:68–79.

    CAS  Article  Google Scholar 

  31. Cruijsen M, Hobo W, van der Velden WJFM, Bremmers MEJ, Woestenenk R, Bär B, et al. Addition of 10-day decitabine to fludarabine/total body irradiation conditioning is feasible and induces tumor-associated antigen-specific T cell responses. Biol Blood Marrow Transpl. 2016;22:1000–8.

  32. Cao YG, He Y, Zhang SD, Liu ZX, Zhai WH, Ma QL, et al. Conditioning regimen of 5-day decitabine administration for allogeneic stem cell transplantation in patients with myelodysplastic syndrome and myeloproliferative neoplasms. Biol Blood Marrow Transpl. 2020;26:285–91.

    CAS  Article  Google Scholar 

  33. Deeg HJ, Storer B, Slattery JT, Anasetti C, Doney KC, Hansen JA, et al. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood. 2002;100:1201–7.

    CAS  Article  Google Scholar 

  34. Zhang XH, Chen J, Han MZ, Huang H, Jiang EL, Jiang M, et al. The consensus from the Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update. J Hematol Oncol. 2021;14:145.

    Article  Google Scholar 

  35. Sobecks RM, Rybicki L, Yurch M, Kalaycio M, Dean R, Andresen S, et al. Intravenous compared with oral busulfan as preparation for allogeneic hematopoietic progenitor cell transplantation for AML and MDS. Bone Marrow Transpl. 2012;47:633–8.

    CAS  Article  Google Scholar 

  36. Ben-Barouch S, Cohen O, Vidal L, Avivi I, Ram R. Busulfan fludarabine vs busulfan cyclophosphamide as a preparative regimen before allogeneic hematopoietic cell transplantation: systematic review and meta-analysis. Bone Marrow Transpl. 2016;51:232–40.

    CAS  Article  Google Scholar 

  37. Valdez BC, Li Y, Murray D, Corn P, Champlin RE, Andersson BS. 5-Aza-2’-deoxycytidine sensitizes busulfan-resistant myeloid leukemia cells by regulating expression of genes involved in cell cycle checkpoint and apoptosis. Leuk Res. 2010;34:364–72.

    CAS  Article  Google Scholar 

  38. Valdez BC, Tang X, Li Y, Murray D, Liu Y, Popat U, et al. Epigenetic modification enhances the cytotoxicity of busulfan and 4-hydroperoxycyclophosphamide in AML cells. Exp Hematol. 2018;67:49–59.

    CAS  Article  Google Scholar 

  39. Schroeder T, Wegener N, Lauseker M, Rautenberg C, Nachtkamp K, Schuler E, et al. Comparison between upfront transplantation and different pretransplant cytoreductive treatment approaches in patients with high-risk myelodysplastic syndrome and secondary acute myelogenous leukemia. Biol Blood Marrow Transpl. 2019;25:1550–9.

    Article  Google Scholar 

  40. Malcovati L, Hellström-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122:2943–64.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The present work was supported and funded by the National Natural Science Foundation of China (Nos. 81974003, 81900181, 81370668), Key Scientific Research Project of Henan University (No. 20A320021) and Collaborative Innovation Center of Hematology of China.

Author information

Authors and Affiliations

Authors

Contributions

L-HX and WS conceived the protocol; RZ analyzed, interpreted the data and wrote the manuscript; XL, LVT and HY carried out the statistical analysis; H-FW, YY and Z-DZ revised the manuscript, and all authors critically reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Wei Shi or Ling-Hui Xia.

Ethics declarations

Competing interests

The authors declare no competing interests.

Consent for publication

We have reviewed the final version of the manuscript and approved it for publication.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, R., Lu, X., Tang, L.V. et al. Comparative analysis of Decitabine intensified BUCY2 and BUCY2 conditioning regimen for high-risk MDS patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant (2022). https://doi.org/10.1038/s41409-022-01645-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41409-022-01645-2

Search

Quick links