Abstract
Therapy-related myeloid neoplasms (t-MN), either myelodysplastic neoplasms (t-MDS) or acute myeloid leukemias (t-AML), have a poor prognosis and allogeneic haematopoietic cell transplantation (allo-HCT) represents the only curative option. In this multicenter, registry-based study, we analyzed outcomes of 378 patients undergoing first allo-HCT between 2006–2017 for t-MN arising secondary to lymphoma treatment. Median age was 58 years at allo-HCT; 222 (59%) had a diagnosis of t-MDS and 156 (41%) of t-AML, respectively. At the time of allo-HCT, 46% of t-MN cases were reported as in complete remission (CR) and 15% of lymphomas were recorded as not in remission. A reduced intensity conditioning regimen was used in 70% of cases. For the entire cohort, 5-year OS, and t-MN PFS, relapse incidence and NRM were 32%, 28%, 35% and 37%, respectively. In multivariable analysis, undergoing allo-HCT with t-MN not in CR and older age were associated with significantly worse OS, PFS and NRM. At 5 years post allo-HCT, the relapse incidence of lymphoma was low at 3%, while the rate of secondary malignancies was 8%. This analysis shows the curative potential of allo-HCT for patients with t-MN arising secondary to lymphoma treatment in approximately a third of patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
The datasets generated during and/or analysed during the current study are not routinely available due to data protection of patients enrolled in the EBMT database.
References
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.
Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140:1345–77.
Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka H-M, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140:1200–28.
Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36:1703–19.
Snowden JA, Sánchez-Ortega I, Corbacioglu S, Basak GW, Chabannon C, de la Camara R, et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022. Bone Marrow Transplant. 2022;57:1217–39.
Morton LM, Curtis RE, Linet MS, Schonfeld SJ, Advani PG, Dalal NH, et al. Trends in risk for therapy-related myelodysplastic syndrome/acute myeloid leukemia after initial chemo/immunotherapy for common and rare lymphoid neoplasms, 2000–2018. eClinicalMedicine. 2023;61:102060.
Eichenauer DA, Thielen I, Haverkamp H, Franklin J, Behringer K, Halbsguth T, et al. Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2014;123:1658–64.
Radivoyevitch T, Dean RM, Shaw BE, Brazauskas R, Tecca HR, Molenaar RJ, et al. Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma. Leuk Res. 2018;74:130–6.
Bachiashvili K, Francisco L, Chen Y, Bosworth A, Forman SJ, Bhatia R, et al. Peripheral blood parameter abnormalities precede therapy‐related myeloid neoplasms after autologous transplantation for lymphoma. Cancer. 2022;128:1392–401.
Joelsson J, Wästerlid T, Rosenquist R, Jakobsen LH, El-Galaly TC, Smedby KE, et al. Incidence and time trends of second primary malignancies after non-Hodgkin lymphoma: a Swedish population-based study. Blood Adv. 2022;6:2657–66.
Moreno Berggren D, Garelius H, Willner Hjelm P, Nilsson L, Rasmussen B, Weibull CE, et al. Therapy-related MDS dissected based on primary disease and treatment—a nationwide perspective. Leukemia. 2023;37:1103–12.
Alkhateeb HB, Mohty R, Greipp P, Bansal R, Hathcock M, Rosenthal A, et al. Therapy-related myeloid neoplasms following chimeric antigen receptor T-cell therapy for non-hodgkin lymphoma. Blood Cancer J. 2022;12:113.
Carreras E, Dufour C, Mohty M, Kröger N, editors. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. Cham: Springer International Publishing; 2019. https://doi.org/10.1007/978-3-030-02278-5.
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2009;15:1628–33.
Robin M, De Wreede LC, Schroeder T, Stölzel F, Kröger N, Koster L, et al. Primary cancer matters in therapy-related myeloid neoplasm patients receiving allogeneic hematopoietic cell transplantation: a Study From the Chronic Malignancies Working Party of the EBMT. HemaSphere. 2023;7:e851.
Nabergoj M, Mauff K, Beelen D, Ganser A, Kröger N, Stölzel F, et al. Allogeneic hematopoietic cell transplantation in patients with therapy-related myeloid neoplasm after breast cancer: a study of the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant. 2022;57:1072–8.
Robin M, Wang J, Koster L, Beelen DW, Bornhäuser M, Kroeger N, et al. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in patients with therapy-related myeloid neoplasm: a study from the Chronic Malignancies Working Party of the EBMT. Blood. 2019;134:45–5.
Gatwood KS, Labopin M, Savani BN, Finke J, Socie G, Beelen D, et al. Transplant outcomes for patients with therapy-related acute myeloid leukemia with prior lymphoid malignancy: an ALWP of EBMT study. Bone Marrow Transplant. 2020;55:224–32.
Wenge DV, Wethmar K, Mikesch J-H, Reicherts C, Schliemann C, Mesters R, et al. Allogeneic hematopoietic stem cell transplantation for therapy-related myeloid neoplasms following treatment of a lymphoid malignancy. Leuk Lymphoma. 2021;62:1930–9.
Jaimes-Albornoz D, Mannone L, Nguyen-Quoc S, Chalandon Y, Chevallier P, Mohty M, et al. Allogeneic stem cell transplantation in therapy-related myelodysplasia after autologous transplantation for lymphoma: a retrospective study of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. 2019;25:2366–74.
Kroger N, Brand R, van Biezen A, Zander A, Dierlamm J, Niederwieser D, et al. Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation. Haematologica. 2009;94:542–9.
Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, et al. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012;119:6145–54.
Metheny L, Callander NS, Hall AC, Zhang M-J, Bo-Subait K, Wang H-L, et al. Allogeneic Transplantation to treat therapy-related myelodysplastic syndrome and acute myelogenous leukemia in adults. Transplant Cell Ther. 2021. https://doi.org/10.1016/j.jtct.2021.08.010.
Lee CJ, Labopin M, Beelen D, Finke J, Blaise D, Ganser A, et al. Comparative outcomes of myeloablative and reduced‐intensity conditioning allogeneic hematopoietic cell transplantation for therapy‐related acute myeloid leukemia with prior solid tumor: A report from the acute leukemia working party of the European society for blood and bone marrow transplantation. Am J Hematol. 2019;94:431–8.
Lawless S, Morris C, Eikema D-J, Kostner L, Stoelzel F, Kröger N, et al. Outcomes of allogeneic haematopoietic stem cell transplantation for therapy-related myeloid neoplasms following treatment for myeloma. Blood. 2022;140:4884–5.
Minetto P, Guolo F, Clavio M, Kunkl A, Colombo N, Carminati E, et al. Early minimal residual disease assessment after AML induction with fludarabine, cytarabine and idarubicin (FLAI) provides the most useful prognostic information. Br J Haematol. 2019;184:457–60.
Press RD, Eickelberg G, Froman A, Yang F, Stentz A, Flatley EM, et al. Next‐generation sequencing‐defined minimal residual disease before stem cell transplantation predicts acute myeloid leukemia relapse. Am J Hematol. 2019;94:902–12.
Hoffmann AP, Besch AL, Othus M, Morsink LM, Wood BL, Mielcarek M, et al. Early achievement of measurable residual disease (MRD)-negative complete remission as predictor of outcome after myeloablative allogeneic hematopoietic cell transplantation in acute myeloid leukemia. Bone Marrow Transplant. 2020;55:669–72.
Caballero-Velázquez T, Pérez-López O, Yeguas Bermejo A, Rodríguez Arbolí E, Colado Varela E, Sempere Talens A, et al. Prognostic value of measurable residual disease in patients with AML undergoing HSCT: a multicenter study. Cancers. 2023;15:1609.
Acknowledgements
The authors would like to thank all investigators and data managers in the EBMT participating centres for their excellent contribution. Funding: Funding for this study was indirectly provided by support of the CMWP of the EBMT.
Author information
Authors and Affiliations
Contributions
MN and MR designed the study. MN, MR interpreted the data. MN, MR and DM wrote the first draft of manuscript. DJE analyzed data and interpreted results. All authors contributed to the writing of the manuscript and approved the final version. Additional contributing centers are listed in Supplementary Table 5.
Corresponding author
Ethics declarations
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.
Supplementary information
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.
About this article
Cite this article
Nabergoj, M., Eikema, DJ., Koster, L. et al. Allogeneic haematopoietic cell transplantation for therapy-related myeloid neoplasms arising following treatment for lymphoma: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant 59, 395–402 (2024). https://doi.org/10.1038/s41409-023-02193-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41409-023-02193-z