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Outcomes of pediatric patients who relapse after first HCT for acute leukemia or MDS

Bone Marrow Transplantation volume 56, pages 1866–1875 (2021)Cite this article

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Abstract

Disease relapse remains a major cause of treatment failure in patients receiving allogeneic hematopoietic cell transplantation (alloHCT) for high-risk acute leukemias or myelodysplastic syndromes (MDS). Comprehensive data on outcomes after post-transplant relapse are lacking, especially in pediatric patients. Our objective was to assess the impact of various transplant-, patient-, and disease-related variables on survival and outcomes in patients who relapse after alloHCT. We describe our institutional experience with 221 pediatric patients who experienced disease relapse after their first alloHCT for acute leukemias or MDS between 1990 and 2018. In a multivariable model, being in first complete remission at first alloHCT, longer duration of remission after alloHCT, experiencing GVHD and receiving a transplant in a more recent time period were significantly associated with a higher likelihood of receiving a second alloHCT after post-transplant relapse. Of these variables, only longer interval from alloHCT to relapse, receiving a second alloHCT or DLI, and receiving a transplant in a more recent time period were associated with improved overall survival. Our data support pursuing second alloHCT for patients who have experienced relapse after their first transplant, as that remains the only salvage modality with a reasonable chance of inducing long-term remission.

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Fig. 1: Overall survival from relapse following allogeneic transplantation.
Fig. 2: Subset analysis of overall survival from relapse following allogeneic transplantation.

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References

  1. Eapen M, Raetz E, Zhang MJ, Muehlenbein C, Devidas M, Abshire T, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood. 2006;107:4961–7. https://doi.org/10.1182/blood-2005-12-4942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Klusmann JH, Reinhardt D, Zimmermann M, Kremens B, Vormoor J, Dworzak M, et al. The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study. Haematologica. 2012;97:21–29. https://doi.org/10.3324/haematol.2011.051714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bajwa R, Schechter T, Soni S, Gassas A, Doyle J, Sisler I, et al. Outcome of children who experience disease relapse following allogeneic hematopoietic SCT for hematologic malignancies. Bone Marrow Transpl. 2013;48:661–5. https://doi.org/10.1038/bmt.2012.209.

    Article  CAS  Google Scholar 

  4. Kuhlen M, Willasch AM, Dalle JH, Wachowiak J, Yaniv I, Ifversen M, et al. Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL-SCT 2003/2007 trial. Br J Haematol. 2018;180:82–89. https://doi.org/10.1111/bjh.14965.

    Article  PubMed  Google Scholar 

  5. Naik S, Martinez C, Leung K, Sasa G, Nguyen NY, Wu MF, et al. Outcomes after second hematopoietic stem cell transplantations in pediatric patients with relapsed hematological malignancies. Biol Blood Marrow Transpl. 2015;21:1266–72. https://doi.org/10.1016/j.bbmt.2015.02.024.

    Article  Google Scholar 

  6. Roux C, Tifratene K, Socie G, Galambrun C, Bertrand Y, Rialland F, et al. Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the societe Francophone de greffe de moelle et de therapie cellulaire (SFGM-TC). Bone Marrow Transpl. 2017;52:678–82. https://doi.org/10.1038/bmt.2016.360.

    Article  CAS  Google Scholar 

  7. Uden T, Bertaina A, Abrahamsson J, Ansari M, Balduzzi A, Bourquin JP, et al. Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children. Br J Haematol. 2020;189:745–50. https://doi.org/10.1111/bjh.16441.

    Article  CAS  PubMed  Google Scholar 

  8. Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, et al. Stem-cell transplantation in children with acute lymphoblastic leukemia: A prospective international multicenter trial comparing sibling donors with matched unrelated donors-The ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015;33:1265–74. https://doi.org/10.1200/JCO.2014.58.9747.

    Article  CAS  PubMed  Google Scholar 

  9. de Lima M, Porter DL, Battiwalla M, Bishop MR, Giralt SA, Hardy NM, et al. Proceedings from the National Cancer Institute’s Second International Workshop on the biology, prevention, and treatment of relapse after hematopoietic stem cell transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transpl. 2014;20:4–13. https://doi.org/10.1016/j.bbmt.2013.08.012.

    Article  Google Scholar 

  10. Devillier R, Crocchiolo R, Etienne A, Prebet T, Charbonnier A, Furst S, et al. Outcome of relapse after allogeneic stem cell transplant in patients with acute myeloid leukemia. Leuk Lymphoma. 2013;54:1228–34. https://doi.org/10.3109/10428194.2012.741230.

    Article  PubMed  Google Scholar 

  11. Thanarajasingam G, Kim HT, Cutler C, Ho VT, Koreth J, Alyea EP, et al. Outcome and prognostic factors for patients who relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2013;19:1713–8. https://doi.org/10.1016/j.bbmt.2013.09.011.

    Article  Google Scholar 

  12. Rubnitz JE, Razzouk BI, Lensing S, Pounds S, Pui CH, Ribeiro RC. Prognostic factors and outcome of recurrence in childhood acute myeloid leukemia. Cancer. 2007;109:157–63. https://doi.org/10.1002/cncr.22385.

    Article  PubMed  Google Scholar 

  13. Eapen M, Giralt SA, Horowitz MM, Klein JP, Wagner JE, Zhang MJ, et al. Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant. Bone Marrow Transpl. 2004;34:721–7. https://doi.org/10.1038/sj.bmt.1704645.

    Article  CAS  Google Scholar 

  14. Kroger N, Bishop M, Giralt S, Wayne A. Third International workshop on the biology, prevention, and treatment of relapse after stem cell transplantation. Bone Marrow Transpl. 2018;53:1–2. https://doi.org/10.1038/bmt.2017.218.

    Article  CAS  Google Scholar 

  15. Arellano ML, Langston A, Winton E, Flowers CR, Waller EK. Treatment of relapsed acute leukemia after allogeneic transplantation: a single center experience. Biol Blood Marrow Transpl. 2007;13:116–23. https://doi.org/10.1016/j.bbmt.2006.09.005.

    Article  Google Scholar 

  16. Bejanyan N, Oran B, Shanley R, Warlick E, Ustun C, Vercellotti G, et al. Clinical outcomes of AML patients relapsing after matched-related donor and umbilical cord blood transplantation. Bone Marrow Transpl. 2014;49:1029–35. https://doi.org/10.1038/bmt.2014.116.

    Article  CAS  Google Scholar 

  17. Matsumoto K, Yamamoto W, Ogusa E, Ishigatsubo Y, Kanamori H. Prognostic index for relapsed acute leukemia after allogeneic stem cell transplant. Leuk Lymphoma. 2014;55:2808–12. https://doi.org/10.3109/10428194.2014.896004.

    Article  PubMed  Google Scholar 

  18. Lee JW, Jang PS, Chung NG, Cho B, Kim HK. Treatment of children with acute myeloid leukaemia who relapsed after allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2013;160:80–86. https://doi.org/10.1111/bjh.12074.

    Article  PubMed  Google Scholar 

  19. Dahlberg A, Leisenring W, Bleakley M, Meshinchi S, Baker KS, Summers C, et al. Prognosis of relapse after hematopoietic cell transplant (HCT) for treatment of leukemia or myelodysplastic syndrome (MDS) in children. Bone Marrow Transpl. 2019;54:1337–45. https://doi.org/10.1038/s41409-019-0438-z.

    Article  CAS  Google Scholar 

  20. Lund TC, Ahn KW, Tecca HR, Hilgers MV, Abdel-Azim H, Abraham A, et al. Outcomes after second hematopoietic cell transplantation in children and young adults with relapsed acute leukemia. Biol Blood Marrow Transpl. 2019;25:301–6. https://doi.org/10.1016/j.bbmt.2018.09.016.

    Article  Google Scholar 

  21. Rujkijyanont P, Morris C, Kang G, Gan K, Hartford C, Triplett B, et al. Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia. Blood Cancer J. 2013;3:e137. https://doi.org/10.1038/bcj.2013.39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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 

  23. Schmid C, Labopin M, Nagler A, Niederwieser D, Castagna L, Tabrizi R, et al. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood. 2012;119:1599–606. https://doi.org/10.1182/blood-2011-08-375840.

    Article  CAS  PubMed  Google Scholar 

  24. Ruutu T, de Wreede LC, van Biezen A, Brand R, Mohty M, Dreger P, et al. Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT. Bone Marrow Transpl. 2015;50:1542–50. https://doi.org/10.1038/bmt.2015.186.

    Article  CAS  Google Scholar 

  25. Orti G, Sanz J, Bermudez A, Caballero D, Martinez C, Sierra J, et al. Outcome of second allogeneic hematopoietic cell transplantation after relapse of myeloid malignancies following allogeneic hematopoietic cell transplantation: a retrospective cohort on behalf of the Grupo Espanol de Trasplante Hematopoyetico. Biol Blood Marrow Transpl. 2016;22:584–8. https://doi.org/10.1016/j.bbmt.2015.11.012.

    Article  Google Scholar 

  26. Vrhovac R, Labopin M, Ciceri F, Finke J, Holler E, Tischer J, et al. Second reduced intensity conditioning allogeneic transplant as a rescue strategy for acute leukaemia patients who relapse after an initial RIC allogeneic transplantation: analysis of risk factors and treatment outcomes. Bone Marrow Transpl. 2016;51:186–93. https://doi.org/10.1038/bmt.2015.221.

    Article  CAS  Google Scholar 

  27. Bosi A, Laszlo D, Labopin M, Reffeirs J, Michallet M, Gluckman E, et al. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol. 2001;19:3675–84. https://doi.org/10.1200/JCO.2001.19.16.3675.

    Article  CAS  PubMed  Google Scholar 

  28. Hosing C, Saliba RM, Shahjahan M, Estey EH, Couriel D, Giralt S, et al. Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia. Bone Marrow Transpl. 2005;36:157–62. https://doi.org/10.1038/sj.bmt.1705011.

    Article  CAS  Google Scholar 

  29. Radich JP, Sanders JE, Buckner CD, Martin PJ, Petersen FB, Bensinger W, et al. Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens. J Clin Oncol. 1993;11:304–13. https://doi.org/10.1200/JCO.1993.11.2.304.

    Article  CAS  PubMed  Google Scholar 

  30. Fan Y, Artz AS, van Besien K, Stock W, Larson RA, Odenike O, et al. Outcomes following second allogeneic stem cell transplant for disease relapse after T cell depleted transplant correlate with remission status and remission duration after the first transplant. Exp Hematol Oncol. 2019;8:1. https://doi.org/10.1186/s40164-018-0125-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Thakar MS, Forman SJ. ASH evidence-based guidelines: is there a role for second allogeneic transplant after relapse? Hematology Am Soc Hematol Educ Program 2009:414–8. https://doi.org/10.1182/asheducation-2009.1.414.

  32. NHS England Specialised Services Clinical Reference Group for Blood and Marrow Transplantation. Second allogenic haematopoietic stem cell transplant for relapsed disease 2017.

  33. Michallet M, Tanguy ML, Socie G, Thiebaut A, Belhabri A, Milpied N, et al. Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de moelle (SFGM). Br J Haematol. 2000;108:400–7. https://doi.org/10.1046/j.1365-2141.2000.01851.x.

    Article  CAS  PubMed  Google Scholar 

  34. Kato M, Horikoshi Y, Okamoto Y, Takahashi Y, Hasegawa D, Koh K, et al. Second allogeneic hematopoietic SCT for relapsed ALL in children. Bone Marrow Transpl. 2012;47:1307–11. https://doi.org/10.1038/bmt.2012.29.

    Article  CAS  Google Scholar 

  35. Menon NN, Jenkins LM, Cui H, Jenkins C, Anwer F, Yeager AM, et al. Factors associated with improved outcomes after second allogeneic hematopoietic cell transplantation for relapsed pediatric leukemia. Ann Hematol. 2016;95:637–44. https://doi.org/10.1007/s00277-016-2599-9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Keith A. Laycock, PhD, ELS, for the scientific editing of the manuscript. We would like to thank our colleagues, advanced practice providers, nurses, and other healthcare professional who participated in patient care. We would also like to thank the parents, who entrusted the care of our children to us. This work was supported by the American Society of Hematology (Scholar Award to AS) and the American Lebanese Syrian Associated Charities (ALSAC).

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Authors and Affiliations

  1. Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Akshay Sharma, Ying Li, Aimee C. Talleur, Ali Suliman, Amr Qudeimat, Ashok Srinivasan, Ewelina Mamcarz, Renee Madden, Stephen Gottschalk & Brandon M. Triplett

  2. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Sujuan Huang & Cheng Cheng

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Correspondence to Akshay Sharma or Brandon M. Triplett.

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Conflict of interest

AS’s institution receives support for the conduct of industry sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis. AS has received consulting fee from Spotlight Therapeutics. Both are unrelated to the data presented in this manuscript. BMT has received financial support for travel from Miltenyi Biotec. The remaining authors do not have any conflicts of interest to disclose.

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Sharma, A., Li, Y., Huang, S. et al. Outcomes of pediatric patients who relapse after first HCT for acute leukemia or MDS. Bone Marrow Transplant 56, 1866–1875 (2021). https://doi.org/10.1038/s41409-021-01267-0

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