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QoL and Patients' Care

Long-term systolic function in children and young adults after hematopoietic stem cell transplant

Bone Marrow Transplantation volume 52, pages 1443–1447 (2017)Cite this article

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Abstract

Congestive heart failure and subclinical left ventricular systolic dysfunction (LVSD) affect long-term survivors of hematopoietic stem cell transplant (HSCT). Echocardiographic measurements of global longitudinal and circumferential strain have shown promise in identifying subclinical LVSD in cancer survivors. We analyzed echocardiograms in 95 children and young adults with malignancies or bone marrow failure syndromes performed before HSCT and 1–6 years after HSCT. We additionally measured the biomarkers soluble suppression of tumorigenicity-2 (sST-2) and cardiac troponin-I (cTn-I) in the same children through 49 days post HSCT. Ejection fraction (EF) after HSCT was unchanged from baseline (baseline: z-score −0.73 vs long-term follow up: −0.44, P=0.11). Global longitudinal strain was unchanged from baseline (−20.66 vs −20.74%, P=0.90) as was global circumferential strain (−24.3 vs −23.5%, P=0.32). Levels of sST-2 were elevated at all time points compared with baseline samples and cTn-I was elevated at days 14 and 28. Cardiac biomarkers at any time point did not correlate with long-term follow-up EF. In children and young adult survivors of HSCT, EF was unchanged in the first years after HSCT. Elevation in cardiac biomarkers occurring after HSCT suggest subclinical cardiac injury occurs in many patients and long-term monitoring for LVSD should continue.

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References

  1. Dandoy CE, Davies SM, Hirsch R, Chima RS, Paff Z, Cash M et al. Abnormal echocardiography 7 days after stem cell transplantation may be an early indicator of thrombotic microangiopathy. Biol Blood Marrow Transplant 2015; 21: 113–118.

    Article  Google Scholar 

  2. Rotz SJ, Ryan TD, Jodele S, Jefferies JL, Lane A, Pate A et al. The injured heart: early cardiac effects of hematopoietic stem cell transplantation in children and young adults. Bone Marrow Transplant (e-pub ahead of print 10 April 2017; doi:10.1038/bmt.2017.62).

  3. Dandoy CE, Jodele S, Paff Z, Hirsch R, Ryan TD, Jefferies JL et al. Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients. Pediatr Blood Cancer (e-pub ahead of print 8 March 2017; doi:10.1002/pbc.26513).

  4. Pfeiffer T, Rotz S, Ryan T, Hirsch R, Taylor M, Chima R et al. Pericardial effusion requiring surgical intervention after stem cell transplantation: a case series. Bone Marrow Transplant 2016; 52: 630–633.

    Article  Google Scholar 

  5. Uderzo C, Pillon M, Corti P, Tridello G, Tana F, Zintl F et al. Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working Parties. Bone Marrow Transplant 2007; 39: 667–675.

    Article  CAS  Google Scholar 

  6. Fujimaki K, Maruta A, Yoshida M, Sakai R, Tanabe J, Koharazawa H et al. Severe cardiac toxicity in hematological stem cell transplantation: predictive value of reduced left ventricular ejection fraction. Bone Marrow Transplant 2001; 27: 307–310.

    Article  CAS  Google Scholar 

  7. Lehmann S, Isberg B, Ljungman P, Paul C . Cardiac systolic function before and after hematopoietic stem cell transplantation. Bone Marrow Transplant 2000; 26: 187–192.

    Article  CAS  Google Scholar 

  8. Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C et al. Cardiovascular complications of cancer therapy diagnosis, pathogenesis, and management. Circulation 2004; 109: 3122–3131.

    Article  Google Scholar 

  9. Faraci M, Békássy AN, Fazio V, De, Tichelli A, Dini G . Non-endocrine late complications in children after allogeneic haematopoietic SCT. Bone Marrow Transplant 2008; 41: S49–S57.

    Article  CAS  Google Scholar 

  10. Murbraech K, Smeland KB, Holte H, Loge JH, Lund MB, Wethal T et al. Heart failure and asymptomatic left ventricular systolic dysfunction in lymphoma survivors treated with autologous stem-cell transplantation: a national cross-sectional study. J Clin Oncol 2015; 33: 2683–2691.

    Article  Google Scholar 

  11. Genberg M, Öberg A, Andrén B, Hedenström H, Frisk P, Flachskampf FA . Cardiac function after hematopoietic cell transplantation: an echocardiographic cross-sectional study in young adults treated in childhood. Pediatr Blood Cancer 2015; 62: 143–147.

    Article  CAS  Google Scholar 

  12. Künkele A, Engelhard M, Hauffa BP, Mellies U, Müntjes C, Hüer C et al. Long-term follow-up of pediatric patients receiving total body irradiation before hematopoietic stem cell transplantation and post-transplant survival of >2 years. Pediatr Blood Cancer 2013; 60: 1792–1797.

    Article  Google Scholar 

  13. Thavendiranathan P, Poulin F, Lim K-D, Plana JC, Woo A, Marwick TH . Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol 2014; 63: 2751–2768.

    Article  Google Scholar 

  14. Hare JL, Brown JK, Leano R, Jenkins C, Woodward N, Marwick TH . Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab. Am Heart J 2009; 158: 294–301.

    Article  CAS  Google Scholar 

  15. Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging 2012; 5: 596–603.

    Article  Google Scholar 

  16. Mavinkurve-Groothuis AM, Marcus KA, Pourier M, Loonen J, Feuth T, Hoogerbrugge PM et al. Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study. Eur Heart J Cardiovasc Imaging 2013; 14: 562–569.

    Article  Google Scholar 

  17. Rotz SJ, Ryan TD, Hlavaty J, George SA, El-Bietar J, Dandoy CE . Cardiotoxicity and cardiomyopathy in children and young adult survivors of hematopoietic stem cell transplant. Pediatr Blood Cancer (e-pub ahead of print 28 April 2017).

  18. Lipshultz SE, Miller TL, Scully RE, Lipsitz SR, Rifai N, Silverman LB et al. Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes. J Clin Oncol 2012; 30: 1042–1049.

    Article  CAS  Google Scholar 

  19. Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M, Salvatici M et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol 2010; 28: 3910–3916.

    Article  CAS  Google Scholar 

  20. Kohli P, Bonaca MP, Kakkar R, Kudinova AY, Scirica BM, Sabatine MS et al. Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial. Clin Chem 2012; 58: 257–266.

    Article  CAS  Google Scholar 

  21. Weinberg EO, Shimpo M, Keulenaer GW, De, MacGillivray C, Tominaga S, Solomon SD et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 2002; 106: 2961–2966.

    Article  CAS  Google Scholar 

  22. Rehman SU, Mueller T, Januzzi JL . Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol 2008; 52: 1458–1465.

    Article  CAS  Google Scholar 

  23. Horacek J, Pudil R, Tichy M, Jebavy L, Zak P, Slovacek L et al. Biochemical markers and assessment of cardiotoxicity during preparative regimen and hematopoietic cell transplantation in acute leukemia. Exp Oncol 2007; 29: 243–247.

    CAS  PubMed  Google Scholar 

  24. Jodele S, Laskin BL, Dandoy CE, Myers KC, El-Bietar J, Davies SM et al. A new paradigm: diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev 2015; 29: 191–204.

    Article  Google Scholar 

  25. Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE et al. Bone-marrow transplantation. N Engl J Med 1975; 292: 895–902.

    Article  CAS  Google Scholar 

  26. Przepiorka D, Weisdorf D, Martin P, Klingemann H, Beatty P, Hows J et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  27. Colan SD. Normal Echocardiographic Values for Cardiovascular Structures. Echocardiography in Pediatric and Congenital Heart Disease: From Fetus to Adult, 2 edn. Wiley Online Library Oxford, UK, 2009, pp, 883–901.

  28. Levy PT, Machefsky A, Sanchez AA, Patel MD, Rogal S, Fowler S et al. Reference ranges of left ventricular strain measures by two-dimensional speckle-tracking echocardiography in children: a systematic review and meta-analysis. J Am Soc Echocardiogr 2016; 29: 209–225.

    Article  Google Scholar 

  29. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28: 1–39.

    Article  Google Scholar 

  30. Leger KJ, Cushing-Haugen K, Hansen JA, Fan W, Leisenring WM, Martin PJ et al. Clinical and genetic determinants of cardiomyopathy risk among hematopoietic cell transplantation survivors. Biol Blood Marrow Transplant 2016; 22: 1094–1101.

    Article  Google Scholar 

  31. Armenian SH, Sun C-L, Shannon T, Mills G, Francisco L, Venkataraman K et al. Incidence and predictors of congestive heart failure after autologous hematopoietic cell transplantation. Blood 2011; 118: 6023–6029.

    Article  CAS  Google Scholar 

  32. Armenian SH, Sun C-L, Francisco L, Steinberger J, Kurian S, Wong FL et al. Late congestive heart failure after hematopoietic cell transplantation. J Clin Oncol 2008; 26: 5537–5543.

    Article  Google Scholar 

  33. Tichelli A, Bhatia S, Socié G . Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation. Br J Haematol 2008; 142: 11–26.

    Article  Google Scholar 

  34. DeFilipp Z, Duarte RF, Snowden JA, Majhail NS, Greenfield DM, Miranda JL et al. Metabolic syndrome and cardiovascular disease after hematopoietic cell transplantation: screening and preventive practice recommendations from the CIBMTR and EBMT. Biol Blood Marrow Transplant 2016; 22: 1493–1503.

    Article  Google Scholar 

  35. Tichelli A, Bucher C, Rovó A, Stussi G, Stern M, Paulussen M et al. Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation. Blood 2007; 110: 3463–3471.

    Article  CAS  Google Scholar 

  36. Bovelli D, Plataniotis G, Roila F, EGW Group and others. Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Ann Oncol 2010; 21: v277–v282.

    Article  Google Scholar 

  37. Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, Giacomi GDe et al. Anthracycline-induced cardiomyopathyclinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 2010; 55: 213–220.

    Article  CAS  Google Scholar 

  38. Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 2015; 131: 1981–1988.

    Article  CAS  Google Scholar 

  39. Bosch X, Rovira M, Sitges M, Domènech A, Ortiz-Pérez JT, Caralt T M de et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: The OVERCOME Trial. J Am Coll Cardiol 2013; 61: 2355–2362.

    Article  CAS  Google Scholar 

  40. Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 2006; 114: 2474–2481.

    Article  CAS  Google Scholar 

  41. Ewer MS, Ewer SM . Cardiotoxicity of anticancer treatments. Nat Rev Cardiol 2015; 12: 547–558.

    Article  CAS  Google Scholar 

  42. ElMarsafawy H, Matter M, Sarhan M, El-Ashry R, Al-Tonbary Y . Assessment of myocardial function in children before and after autologous peripheral blood stem cell transplantation. Echocardiography 2015; 33: 82–89.

    Article  Google Scholar 

  43. Vander Lugt MT, Braun TM, Hanash S, Ritz J, Ho VT, Antin JH et al. ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. N Engl J Med 2013; 369: 529–539.

    Article  CAS  Google Scholar 

  44. Rotz SJ, Dandoy CE, Davies SM . ST2 and endothelial injury as a link between GVHD and microangiopathy. N Engl J Med 2017; 376: 1189–1190.

    Article  Google Scholar 

  45. Armenian SH, Chemaitilly W, Chen M, Chow EJ, Duncan CN, Jones LW et al. National Institutes of Health hematopoietic cell transplantation late effects initiative: the Cardiovascular Disease and Associated Risk Factors Working Group report. Biol Blood Marrow Transplant 2017; 23: 201–210.

    Article  Google Scholar 

  46. Chow EJ, Anderson L, Baker KS, Bhatia S, Guilcher GM, Huang JT et al. Late effects surveillance recommendations among survivors of childhood hematopoietic cell transplantation: a Children’s Oncology Group Report. Biol Blood Marrow Transplant 2016; 22: 782–795.

    Article  Google Scholar 

  47. Majhail NS, Rizzo JD, Lee SJ, Aljurf M, Atsuta Y, Bonfim C et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Hematol Oncol Stem Cell Ther 2012; 5: 1–30.

    Article  CAS  Google Scholar 

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Acknowledgements

Funding for this study was provided by a grant from the University of Cincinnati Cancer Institute Cancer Survivorship Program.

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Authors and Affiliations

  1. Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    S J Rotz, C E Dandoy, S Jodele, A Lane, J A El-Bietar & S M Davies

  2. Division of Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    M D Taylor, J L Jefferies, A W Powell & T D Ryan

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  1. S J Rotz
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Correspondence to S J Rotz.

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Rotz, S., Dandoy, C., Taylor, M. et al. Long-term systolic function in children and young adults after hematopoietic stem cell transplant. Bone Marrow Transplant 52, 1443–1447 (2017). https://doi.org/10.1038/bmt.2017.162

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