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High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma

Bone Marrow Transplantation volume 56, pages 2690–2696 (2021)Cite this article

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Abstract

Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied 1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing the prognostic role of LDH at admission for survival (OS), progression-free survival (PFS), relapse incidence (RI), and nonrelapse mortality (NRM). In non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML), higher than median LDH had an adverse effect on survival. The prognostic significance was strongest in AML, with higher LDH levels having lower 1-and 3-year survival 69.2% vs. 50.8%, P < 0.001 and 51.9% vs. 39.2%, P < 0.001, respectively, reduced 1-and 3-year PFS 62.4% vs. 42.1%, P < 0.001 48% vs. 35.2%, P < 0.001, respectively, higher cumulative incidence of 1-and 3-year NRM 11% vs. 17.3%, p = 0.01 and 15.7% vs. 19.6%, P = 0.04, and higher 1-and 3-year relapse incidence (RI) 26.7% vs. 40.7%, p < .0001 36.2% vs. 40.7%, respectively, P < 0.0001). In multivariate analysis LDH maintained significant prognostic capacity in OS, PFS and RI. These findings in AML, validated in an independent cohort, suggest that LDH is a readily available tool that could be integrated into transplant risk assessments to aid decision-making and identify high-risk patients who may benefit from post-transplant pharmacological or cellular strategies.

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References

  1. Potdar R, Varadi G, Fein J, Labopin M, Nagler A, Shouval R. Prognostic scoring systems in allogeneic hematopoietic stem cell transplantation: where do we stand? Biol Blood Marrow Transpl. 2017;23:1839–46.

    Article  Google Scholar 

  2. Carreras E, Dufour C, Mohty M, Kröger N. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. Springer; 2019. pp 77–86.

  3. Armand P, Kim HT, Zhang MJ, Perez WS, Dal Cin PS, Klumpp TR, et al. Classifying cytogenetics in patients with AML in complete remission undergoing allogeneic transplantation: a CIBMTR study. Biol Blood Marrow Transpl. 2012;18:280–8.

    Article  Google Scholar 

  4. Araki D, Wood BL, Othus M, Radich JP, Halpern AB, Zhou Y, et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease-based definition of complete remission? J Clin Oncol. 2016;34:329–36.

    Article  Google Scholar 

  5. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2006;106:2912–9.

    Article  Google Scholar 

  6. Elsawy M, Sorror M. Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation. Bone Marrow Transpl. 2016;51:1283–1300.

    Article  CAS  Google Scholar 

  7. Shouval R, Labopin M, Unger R, Giebel S, Ciceri F, Schmid C, et al. Prediction of hematopoietic stem cell transplantation related mortality- lessons learned from the in-silico approach: a european society for blood and marrow transplantation acute leukemia working party data mining study. PLoS ONE. 2016;11:e0150637.

    Article  Google Scholar 

  8. Shouval R, Fein JA, Shouval A, Danylesko I, Shem-Tov N, Zlotnik M, et al. External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019;12:1881–90.

    Article  Google Scholar 

  9. Dimopoulos MA, Barlogie B, Smith TL, Alexanian R. High serum lactate dehydrogenase level as a marker for drug resistance and short survival in multiple myeloma. Ann Intern Med. 1991;115:931–5.

    Article  CAS  Google Scholar 

  10. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. 2015;33:2863–9.

    Article  CAS  Google Scholar 

  11. Kim SJ, Hong JS, Chang MH, Kim JA, Kwak JY, Kim JS, et al. Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study. OncoTargets. 2016;7:72033–43.

    Article  Google Scholar 

  12. Schneider RJ, Seibert K, Passe S, Little C, Gee T, Lee BJ 3rd, et al. Prognostic significance of serum lactate dehydrogenase in malignant lymphoma. Cancer. 1980;46:139–43.

    Article  CAS  Google Scholar 

  13. Wimazal F, Sperr WR, Kundi M, Meidlinger P, Fonatsch C, Jordan JH, et al. Prognostic value of lactate dehydrogenase activity in myelodysplastic syndromes. Leuk Res. 2001;25:287–94.

    Article  CAS  Google Scholar 

  14. Germing U, Hildebrandt B, Pfeilstöcker M, Nösslinger T, Valent P, Fonatsch C, et al. Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). Leukemia. 2005;19:2223–31.

    Article  CAS  Google Scholar 

  15. García R, Hernández JM, Caballero MD, González M, Galende J, del Cañizo MC, et al. Serum lactate dehydrogenase level as a prognostic factor in Hodgkin’s disease. Br J Cancer. 1993;68:1227–31.

    Article  Google Scholar 

  16. Röllig C, Thiede C, Gramatzki M, Aulitzky W, Bodenstein H, Bornhäuser M, et al. A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood. 2010;116:971–8.

    Article  Google Scholar 

  17. Haferlach T, Schoch C, Löffler H, Gassmann W, Kern W, Schnittger S, et al. Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies. J Clin Oncol. 2003;21:256–65.

    Article  Google Scholar 

  18. Fanin R, Zuffa E, Fasola G, Damiani D, Gallizia C, Michieli MG, et al. Serum lactate dehydrogenase is an important risk determinant in acute lymphocytic leukemia. Haematologica. 1989;74:161–5.

    CAS  PubMed  Google Scholar 

  19. Paltiel O, Rubinstein C, Or R, Nagler A, Gordon L, Deutsch L, et al. Factors associated with survival in patients with progressive disease following autologous transplant for lymphoma. Bone Marrow Transpl. 2003;31:565–9.

    Article  CAS  Google Scholar 

  20. Bolwell B, Goormastic M, Andresen S. Durability of remission after ABMT for NHL: the importance of the 2-year evaluation point. Bone Marrow Transpl. 1997;19:443–8.

    Article  CAS  Google Scholar 

  21. Armand P, Kim HT, Ho VT, Cutler CS, Koreth J, Antin JH, et al. Allogeneic transplantation with reduced-intensity conditioning for Hodgkin and non-Hodgkin lymphoma: importance of histology for outcome. Biol Blood Marrow Transpl. 2008;14:418–25.

    Article  CAS  Google Scholar 

  22. Shouval R, Teper O, Fein JA, Danylesko I, Shem Tov N, Yerushalmi R, et al. LDH and renal function are prognostic factors for long-term outcomes of multiple myeloma patients undergoing allogeneic hematopoietic stem cell. Bone Marrow Transpl. 2020;55:1736–43.

    Article  CAS  Google Scholar 

  23. Kalaycio M, Rybicki L, Pohlman B, Dean R, Sweetenham J, Andresen S, et al. Elevated lactate dehydrogenase is an adverse predictor of outcome in HLA-matched sibling bone marrow transplant for acute myelogenous leukemia. Bone Marrow Transpl. 2007;40:753–8.

    Article  CAS  Google Scholar 

  24. Mehta J, Gordon LI, Tallman MS, Winter JN, Evens AM, Frankfurt O, et al. Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially? Bone Marrow Transpl. 2006;38:95–100.

    Article  CAS  Google Scholar 

  25. Morishita T, Ichiki T, Okabe M, Kawaguchi Y, Ohbiki M, Osaki M, et al. Pretransplant increasing rate of lactate hydrogenase during treatment free period predicts transplant outcomes for patients not in remission. HemaSphere. 2019;3:336.

    Article  Google Scholar 

  26. Sivgin S, Ozenmis T, Kaynar L. Predictive value of pretransplant serum lactate dehydrogenase (LDH) levels for survival in patients who have undergone allogeneic hematopoietic stem cell transplantation (allo HSCT). J Stem Cell Stem Res Ther. 2012;2:1.

    Google Scholar 

  27. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71.

    Article  CAS  Google Scholar 

  28. 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 Transpl. 2009;15:1628–33.

    Article  Google Scholar 

  29. Blaise D, Castagna L. Do different conditioning regimens really make a difference? Hematology Am Soc Hematol Educ Program. 2012;2012:237–45.. https://doi.org/10.1182/asheducation-2012.1.237.

  30. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.

    Article  Google Scholar 

  31. Scrucca L, Santucci A, Aversa F. Regression modeling of competing risk using R: an in depth guide for clinicians. Bone Marrow Transpl. 2010;45:1388–95.

    Article  CAS  Google Scholar 

  32. Estey EH. Acute myeloid leukamia: 2019 update on risk-stratification and management. Am J Hematol. 2018;93:1267–91.

    Article  Google Scholar 

  33. Holbrook JJ, Liljas A, Steindel SJ, Rossmann MG. Lactate dehydrogenase. In: Boyer PD, editor. The Enzymes. 3rd ed. Vol. 11. New York, NY:  Academic Press; 1975. p. 191–292.

  34. Walaa Fikry ME. Lactate Dehydrogenase (LDH) as a prognostic marker in Acute Leukaemia “Quantitative Method”. J Blood Disord Transfus. 2017;8:1–7.

    Google Scholar 

  35. Sepulveda J. Chapter 9 - challenges in routine clinical chemistry analysis: proteins and enzymes. In: Dasgupta A, Sepulveda JL, editors. Accurate results in the clinical laboratory. San Diego: Elsevier; 2013. p. 131–48.

  36. Artz AS, Wickrema A, Dinner S, Godley LA, Kocherginsky M, Odenike O, et al. Pre-treatment C-reactive Protein(CRP) is a predictor for allogeneic hematopoietic cell transplantation outcomes. Biol Blood Marrow Transpl. 2008;14:1209–16.

    Article  Google Scholar 

  37. Jordan K, Christensen I, Heilmann C, Sengeløv H, Müller KG. Pre-transplant C-reactive protein as a prognostic marker in allogeneic stem cell transplantation. Scand J Immunol. 2014;79:206–13.

    Article  CAS  Google Scholar 

  38. Pavlů J, Kew AK, Taylor-Roberts B, Auner HW, Marin D, Olavarria E, et al. Optimizing patient selection for myeloablative allogeneic hematopoietic cell transplantation in chronic myeloid leukemia in chronic phase. Blood. 2010;115:4018–20.

    Article  Google Scholar 

  39. Patel A, Szydlo R, Auner HW, Kanfer EJ, MacDonald DH, Milojkovic D, et al. C-reactive protein prior to myeloablative allogeneic haematopoietic cell transplantation identifies patients at risk of early and long term mortality. Br J Haematol. 2016;180:889–92.

    Article  Google Scholar 

  40. Andersen J, Heilmann C, Jacobsen N, Nielsen C, Bendtzen K, Müller K. Differential effect on conditioning regimens on cytokine responses during allogeneic stem cell transplantation. Bone Marrow Transplant. 2006;37:635–40.

    Article  CAS  Google Scholar 

  41. Shouval R, Fein JA, Labopin M, Cho C, Bazarbachi A, Baron F, et al. Development and validation of a disease risk stratification system for patients with haematological malignancies: a retrospective cohort study of the European Society for Blood and Marrow Transplantation registry. Lancet Haematol. 2021;3:205–15.

    Article  Google Scholar 

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Acknowledgements

Authors at Imperial College Healthcare NHS Trust and Imperial College are supported by the NIHR BRC. This research was not directly funded and authors are independent of funders. The authors are grateful to patient data managers David Slade and Farah O’Boyle, and other clinical and laboratory staff at Imperial College Healthcare NHS Trust.

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Author notes

  1. These authors contributed equally: Angharad Pryce, Roni Shouval.

Authors and Affiliations

  1. Hematology Division and BMT, Chaim Sheba Medical Center, Tel Hashomer and Tel Aviv University, Tel Aviv-Yafo, Israel

    Mika Geva, Roni Shouval, Joshua A. Fein, Ivetta Danylesko, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni & Arnon Nagler

  2. Centre for Haematology, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London, UK

    Angharad Pryce, Richard Szydlo & Jiri Pavlu

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  1. Mika Geva
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Contributions

MG, RS and AN planned the study. MG and RS performed the analysis and wrote the manuscript. AP, RS and JP undertook the data collection and analysis of validation study and AP co-authored manuscript. Additional input from all the authors to develop and review the final manuscript (JF, ID, NS, RY, AS), and all had full access to all of the data.

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Correspondence to Mika Geva.

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Geva, M., Pryce, A., Shouval, R. et al. High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma. Bone Marrow Transplant 56, 2690–2696 (2021). https://doi.org/10.1038/s41409-021-01377-9

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