Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-17T15:04:13.498Z Has data issue: false hasContentIssue false

Treatment exposures stratify need for echocardiographic screening in asymptomatic long-term survivors of hematopoietic stem cell transplantation

Published online by Cambridge University Press:  12 February 2019

Seth J. Rotz*
Affiliation:
Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Cleveland Clinic Children’s Hospital, Cleveland, OH, USA
Adam Powell
Affiliation:
Division of Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Kasiani C. Myers
Affiliation:
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Michael D. Taylor
Affiliation:
Division of Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
John L. Jefferies
Affiliation:
Division of Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Adam Lane
Affiliation:
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Javier A. El-Bietar
Affiliation:
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Stella M. Davies
Affiliation:
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Christopher E. Dandoy
Affiliation:
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Thomas D. Ryan
Affiliation:
Division of Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
*
Author for correspondence: Seth J. Rotz, MD, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel: +1 216 444 5517; Fax: +1 216 444 3577; E-mail: [email protected]

Abstract

We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.

Type
Original Article
Copyright
© Cambridge University Press 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Cite this article: Rotz SJ, Powell A, Myers KC, Taylor MD, Jefferies JL, Lane A, El-Bietar JA, Davies SM, Dandoy CE, Ryan TD. (2019) Treatment exposures stratify need for echocardiographic screening in asymptomatic long-term survivors of hematopoietic stem cell transplantation. Cardiology in the Young29: 338–343. doi: 10.1017/S104795111800238X

References

1. Rotz, SJ, Ryan, TD, Jodele, S, et al. The injured heart: early cardiac effects of hematopoietic stem cell transplantation in children and young adults. Bone Marrow Transplant 2017; 52: 11711179.10.1038/bmt.2017.62Google Scholar
2. Pfeiffer, TM, Rotz, SJ, Ryan, TD, et al. Pericardial effusion requiring surgical intervention after stem cell transplantation: a case series. Bone Marrow Transplant 2017; 52: 630633.Google Scholar
3. Dandoy, CE, Jodele, S, Paff, Z, et al. Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients. Pediatr Blood Cancer 2017; 64: e26513.10.1002/pbc.26513Google Scholar
4. Dandoy, CE, Davies, SM, Hirsch, R, et al. Abnormal echocardiography 7 days after stem cell transplantation may be an early indicator of thrombotic microangiopathy. Biol Blood Marrow Transplant 2015; 21: 113118.Google Scholar
5. Murdych, T, Weisdorf, DJ. Serious cardiac complications during bone marrow transplantation at the University of Minnesota, 1977-1997. Bone Marrow Transplant 2001; 28: 283287.Google Scholar
6. 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 2017; 64: e26600.Google Scholar
7. Rotz, SJ, Dandoy, CE, Taylor, MD, et al. Long-term systolic function in children and young adults after hematopoietic stem cell transplant. Bone Marrow Transplant 2017; 52: 14431447.Google Scholar
8. Genberg, M, Oberg, A, Andren, B, Hedenstrom, 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: 143147.10.1002/pbc.25135Google Scholar
9. Kunkele, A, Engelhard, M, Hauffa, BP, 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: 17921797.2+years.+Pediatr+Blood+Cancer+2013;+60:+1792–1797.>Google Scholar
10. Uderzo, C, Pillon, M, Corti, P, 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: 667675.Google Scholar
11. Thavendiranathan, P, Poulin, F, Lim, KD, 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: 27512768.Google Scholar
12. 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: 294301.Google Scholar
13. Sawaya, H, Sebag, IA, Plana, JC, 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: 596603.Google Scholar
14. Covi, S, Ravindranath, Y, Farooqi, A, Savasan, S, Chu, R, Aggarwal, S. Changes in bi-ventricular function after hematopoietic stem cell transplant as assessed by speckle tracking echocardiography. Pediatr Cardiol. 2017.Google Scholar
15. Chow, EJ, Anderson, L, Baker, KS, 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: 782795.Google Scholar
16. DeFilipp, Z, Duarte, RF, Snowden, JA, 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: 14931503.Google Scholar
17. Braunlin, EA, Stauffer, NR, Peters, CH, et al. Usefulness of bone marrow transplantation in the Hurler syndrome. Am J Cardiol 2003; 92: 882886.Google Scholar
18. Mariotti, E, Agostini, A, Angelucci, E, Lucarelli, G, Sgarbi, E, Picano, E. Reduced left ventricular contractile reserve identified by low dose dobutamine echocardiography as an early marker of cardiac involvement in asymptomatic patients with thalassemia major. Echocardiography 1996; 13: 463472.Google Scholar
19. Niss, O, Fleck, R, Makue, F, et al. Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia. Blood 2017; 130: 205213.Google Scholar
20. Rai, P, Niss, O, Malik, P. A reappraisal of the mechanisms underlying the cardiac complications of sickle cell anemia. Pediatr Blood Cancer 2017; 64: e26607.Google Scholar
21. Ryan, TD, Jefferies, JL, Chin, C, et al. Abnormal circumferential strain measured by echocardiography is present in patients with Shwachman–Diamond syndrome despite normal shortening fraction. Pediatr Blood Cancer 2015; 62: 12281231.Google Scholar
22. Toiviainen-Salo, S, Pitkanen, O, Holmstrom, M, et al. Myocardial function in patients with Shwachman–Diamond syndrome: aspects to consider before stem cell transplantation. Pediatr Blood Cancer 2008; 51: 461467.Google Scholar
23. Lai, WW, Mertens, L, Cohen, M, Geva, T. Echocardiography in pediatric and congenital heart disease from fetus to adult. Chichester, West Sussex; Hoboken, NJ: Wiley Blackwell/John Wiley & Sons; 2016.Google Scholar
24. Levy, PT, Machefsky, A, Sanchez, AA, 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: 209225 e206.Google Scholar
25. Lang, RM, Badano, LP, Mor-Avi, V, 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. Eur Heart J Cardiovasc Imaging 2015; 16: 233270.Google Scholar
26. Bennett, CE, Freudenberger, R. The current approach to diagnosis and management of left ventricular noncompaction cardiomyopathy: review of the literature. Cardiol Res Pract. 2016;2016:5172308.Google Scholar
27. Ramjaun, A, AlDuhaiby, E, Ahmed, S, et al. Echocardiographic detection of cardiac dysfunction in childhood cancer survivors: how long is screening required? Pediatr Blood Cancer 2015; 62: 21972203.Google Scholar
28. Spewak, MB, Williamson, RS, Mertens, AC, Border, WL, Meacham, LR, Wasilewski-Masker, KJ. Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation. Pediatr Blood Cancer 2017; 64: e26367.10.1002/pbc.26367Google Scholar
29. Mulrooney, DA, Yeazel, MW, Kawashima, T, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 2009; 339: b4606.Google Scholar
30. Ewer, MS, Ewer, SM. Cardiotoxicity of anticancer treatments. Nat Rev Cardiol 2015; 12: 620.Google Scholar
31. Wong, FL, Bhatia, S, Landier, W, et al. Cost-effectiveness of the children’s oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure. Ann Intern Med 2014; 160: 672683.10.7326/M13-2498Google Scholar
32. Armstrong, GT, Plana, JC, Zhang, N, et al. Screening adult survivors of childhood cancer for cardiomyopathy: comparison of echocardiography and cardiac magnetic resonance imaging. J Clin Oncol 2012; 30: 28762884.Google Scholar
33. Silber, JH, Cnaan, A, Clark, BJ, et al. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol 2004; 22: 820828.10.1200/JCO.2004.06.022Google Scholar
34. Gulati, G, Heck, SL, Ree, AH, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2×2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J 2016; 37: 16711680.Google Scholar
35. Cardinale, D, Colombo, A, Sandri, MT, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006; 114: 24742481.10.1161/CIRCULATIONAHA.106.635144Google Scholar
36. Cardinale, D, Colombo, A, Lamantia, G, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 2010; 55: 213220.Google Scholar