Annals of Hematology

, Volume 91, Issue 12, pp 1929–1935

NT-pro-BNP: not the prognostic all-rounder in elderly patients undergoing allogeneic stem cell transplantation

  • Peter S. Haas
  • Gabriele Ihorst
  • Susanne Schnitzler
  • Ralph Wäsch
  • Reinhard Marks
  • Hartmut Bertz
  • Roland Mertelsmann
  • Jürgen Finke
  • Barbara Deschler
Original Article
  • 156 Downloads

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a curative approach for several diseases predominantly affecting elderly patients. Overall survival is compromised by treatment-related mortality (TRM), GvHD, and relapse. Pretransplant clinical risk indicators in elderly patients qualifying for HCT are highly desirable. Pro-BNP is known as a predictor of death in patients with an increasing variety of clinical conditions and frequently used as a routine parameter for organ complications in the allogeneic transplant setting without well-established scientific evidence. Our hypothesis was that pre-HCT NT-pro-BNP could aid in identifying elderly patients at risk for early mortality. We retrospectively evaluated NT-pro-BNP values in 177 consecutive patients of ≥60 years HCT (2005–2010). In 29.4 % of cases, NT-pro-BNP values were within our institute's normal range (<125 pg/ml). Analysis of different NT-pro-BNP cutoff points by receiver operating characteristics curve for mortality at day +100 revealed no single cutoff value with satisfying specificity and sensitivity. The individual outcome of patients with extremely high NT-pro-BNP values was not associated with an increase in mortality or cardiovascular morbidity. NT-pro-BNP values of patients succumbing to TRM did not differ significantly from those alive or having died of relapse—median 276 vs. 217 pg/ml. In conclusion, pre-HCT NT-pro-BNP was of no convincing prognostic relevance for day 100 mortality.

Keywords

Elderly Pro-BNP Risk assessment Allogeneic HCT 

References

  1. 1.
    Deschler B, Binek K, Ihorst G, Marks R, Wasch R, Bertz H, Finke J (2010) Prognostic factor and quality of life analysis in 160 patients aged > or =60 years with hematologic neoplasias treated with allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 16(7):967–975. doi:10.1016/j.bbmt.2010.02.004 PubMedCrossRefGoogle Scholar
  2. 2.
    Hertenstein B, Stefanic M, Schmeiser T, Scholz M, Goller V, Clausen M, Bunjes D, Wiesneth M, Novotny J, Kochs M (1994) Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant. J Clin Oncol 12(5):998–1004PubMedGoogle Scholar
  3. 3.
    Kupari M, Volin L, Suokas A, Hekali P, Ruutu T (1990) Cardiac involvement in bone marrow transplantation: serial changes in left ventricular size, mass and performance. J Intern Med 227(4):259–266PubMedCrossRefGoogle Scholar
  4. 4.
    Chow EJ, Mueller BA, Baker KS, Cushing-Haugen KL, Flowers ME, Martin PJ, Friedman DL, Lee SJ (2011) Cardiovascular hospitalizations and mortality among recipients of hematopoietic stem cell transplantation. Ann Intern Med 155(1):21–32. doi:10.1059/0003-4819-155-1-201107050-00004 PubMedGoogle Scholar
  5. 5.
    Nousiainen T, Vanninen E, Jantunen E, Puustinen J, Remes J, Rantala A, Vuolteenaho O, Hartikainen J (2002) Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction. J Intern Med 251(3):228–234PubMedCrossRefGoogle Scholar
  6. 6.
    Goldberg MA, Antin JH, Guinan EC, Rappeport JM (1986) Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Blood 68(5):1114–1118PubMedGoogle Scholar
  7. 7.
    Vanderheyden M, Bartunek J, Goethals M (2004) Brain and other natriuretic peptides: molecular aspects. Eur J Hear Fail 6(3):261–268. doi:10.1016/j.ejheart.2004.01.004 CrossRefGoogle Scholar
  8. 8.
    Payne CJ, Gibson SC, Bryce G, Jardine AG, Berry C, Kingsmore DB (2011) B-type natriuretic peptide predicts long-term survival after major non-cardiac surgery. Br J Anaesth 107(2):144–149. doi:10.1093/bja/aer119 PubMedCrossRefGoogle Scholar
  9. 9.
    Ryding AD, Kumar S, Worthington AM, Burgess D (2009) Prognostic value of brain natriuretic peptide in noncardiac surgery: a meta-analysis. Anesthesiology 111(2):311–319. doi:10.1097/ALN.0b013e3181aaeb11 PubMedCrossRefGoogle Scholar
  10. 10.
    de Lemos JA, McGuire DK, Drazner MH (2003) B-type natriuretic peptide in cardiovascular disease. Lancet 362(9380):316–322. doi:10.1016/S0140-6736(03)13976-1 PubMedCrossRefGoogle Scholar
  11. 11.
    Karthikeyan G, Moncur RA, Levine O, Heels-Ansdell D, Chan MT, Alonso-Coello P, Yusuf S, Sessler D, Villar JC, Berwanger O, McQueen M, Mathew A, Hill S, Gibson S, Berry C, Yeh HM, Devereaux PJ (2009) Is a pre-operative brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide measurement an independent predictor of adverse cardiovascular outcomes within 30 days of noncardiac surgery? A systematic review and meta-analysis of observational studies. J Am Coll Cardiol 54(17):1599–1606. doi:10.1016/j.jacc.2009.06.028 PubMedCrossRefGoogle Scholar
  12. 12.
    Gardner RS, Ozalp F, Murday AJ, Robb SD, McDonagh TA (2003) N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Hear J 24(19):1735–1743CrossRefGoogle Scholar
  13. 13.
    Tsutamoto T, Wada A, Maeda K, Hisanaga T, Maeda Y, Fukai D, Ohnishi M, Sugimoto Y, Kinoshita M (1997) Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation 96(2):509–516PubMedCrossRefGoogle Scholar
  14. 14.
    Levin ER, Gardner DG, Samson WK (1998) Natriuretic peptides. N Engl J Med 339(5):321–328. doi:10.1056/NEJM199807303390507 PubMedCrossRefGoogle Scholar
  15. 15.
    Wang F, Wu Y, Tang L, Zhu W, Chen F, Xu T, Bo L, Li J, Deng X (2012) Brain natriuretic peptide for prediction of mortality in patients with sepsis: a systematic review and meta-analysis. Crit Care 16(3):R74. doi:10.1186/cc11331 PubMedCrossRefGoogle Scholar
  16. 16.
    Lubien E, DeMaria A, Krishnaswamy P, Clopton P, Koon J, Kazanegra R, Gardetto N, Wanner E, Maisel AS (2002) Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings. Circulation 105(5):595–601PubMedCrossRefGoogle Scholar
  17. 17.
    Tang WH, Girod JP, Lee MJ, Starling RC, Young JB, Van Lente F, Francis GS (2003) Plasma B-type natriuretic peptide levels in ambulatory patients with established chronic symptomatic systolic heart failure. Circulation 108(24):2964–2966. doi:10.1161/01.CIR.0000106903.98196.B6 PubMedCrossRefGoogle Scholar
  18. 18.
    Blonde-Cynober F, Morineau G, Estrugo B, Fillie E, Aussel C, Vincent JP (2011) Diagnostic and prognostic value of brain natriuretic peptide (BNP) concentrations in very elderly heart disease patients: specific geriatric cut-off and impacts of age, gender, renal dysfunction, and nutritional status. Arch Gerontol Geriatr 52(1):106–110. doi:10.1016/j.archger.2010.02.010 PubMedCrossRefGoogle Scholar
  19. 19.
    McLean AS, Huang SJ, Nalos M, Tang B, Stewart DE (2003) The confounding effects of age, gender, serum creatinine, and electrolyte concentrations on plasma B-type natriuretic peptide concentrations in critically ill patients. Crit Care Med 31(11):2611–2618. doi:10.1097/01.CCM.0000094225.18237.20 PubMedCrossRefGoogle Scholar
  20. 20.
    Howie JN, Caldwell MA, Dracup K (2003) The measurement of brain natriuretic peptide in heart failure: precision, accuracy, and implications for practice. AACN Clin Issues 14(4):520–531PubMedCrossRefGoogle Scholar
  21. 21.
    Campbell KH, O'Hare AM (2008) Kidney disease in the elderly: update on recent literature. Curr Opin Nephrol Hypertens 17(3):298–303. doi:10.1097/MNH.0b013e3282f5dd90 PubMedCrossRefGoogle Scholar
  22. 22.
    Masuko M, Ito M, Kurasaki T, Yano T, Takizawa J, Toba K, Aoki S, Fuse I, Kodama M, Furukawa T, Aizawa Y (2007) Plasma brain natriuretic peptide during myeloablative stem cell transplantation. Intern Med 46(9):551–555PubMedCrossRefGoogle Scholar
  23. 23.
    Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, Holler E, Finke JM (2008) Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood 112(2):415–425PubMedCrossRefGoogle Scholar
  24. 24.
    Altman DG, Lausen B, Sauerbrei W, Schumacher M (1994) Dangers of using “optimal” cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst 86(11):829–835PubMedCrossRefGoogle Scholar
  25. 25.
    Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106(8):2912–2919PubMedCrossRefGoogle Scholar
  26. 26.
    Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, Storb R, McDonald GB (2010) Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 363(22):2091–2101. doi:10.1056/NEJMoa1004383 PubMedCrossRefGoogle Scholar
  27. 27.
    Martin PJ, Counts GW Jr, Appelbaum FR, Lee SJ, Sanders JE, Deeg HJ, Flowers ME, Syrjala KL, Hansen JA, Storb RF, Storer BE (2010) Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation. J Clin Oncol 28(6):1011–1016. doi:10.1200/JCO.2009.25.6693 PubMedCrossRefGoogle Scholar
  28. 28.
    DeFilippi C, van Kimmenade RR, Pinto YM (2008) Amino-terminal pro-B-type natriuretic peptide testing in renal disease. Am J Cardiol 101(3A):82–88. doi:10.1016/j.amjcard.2007.11.029 PubMedCrossRefGoogle Scholar
  29. 29.
    Morrow DA, Cannon CP, Jesse RL, Newby LK, Ravkilde J, Storrow AB, Wu AH, Christenson RH, Apple FS, Francis G, Tang W (2007) National Academy of Clinical Biochemistry laboratory medicine practice guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem 53(4):552–574. doi:10.1373/clinchem.2006.084194 PubMedCrossRefGoogle Scholar
  30. 30.
    Rodseth RN, Lurati Buse GA, Bolliger D, Burkhart CS, Cuthbertson BH, Gibson SC, Mahla E, Leibowitz DW, Biccard BM (2011) The predictive ability of pre-operative B-type natriuretic peptide in vascular patients for major adverse cardiac events: an individual patient data meta-analysis. J Am Coll Cardiol 58(5):522–529. doi:10.1016/j.jacc.2011.04.018 PubMedCrossRefGoogle Scholar
  31. 31.
    Takatsuka H, Nakajima T, Nomura K, Okikawa Y, Wakae T, Toda A, Itoi H, Okada M, Misawa M, Hara H, Ogawa H (2006) Prognosis value of atrial natriuretic peptide and brain natriuretic peptide for heart failure in patients undergoing allogeneic bone marrow transplantation. Hematology 11(5):351–354. doi:10.1080/10245330600774991 PubMedCrossRefGoogle Scholar
  32. 32.
    Qazilbash MH, Amjad AI, Qureshi S, Qureshi SR, Saliba RM, Khan ZU, Hosing C, Giralt SA, De Lima MJ, Popat UR, Yusuf SW, Champlin RE (2009) Outcome of allogeneic hematopoietic stem cell transplantation in patients with low left ventricular ejection fraction. Biol Blood Marrow Transplant 15(10):1265–1270. doi:10.1016/j.bbmt.2009.06.001 PubMedCrossRefGoogle Scholar
  33. 33.
    Lehmann S, Isberg B, Ljungman P, Paul C (2000) Cardiac systolic function before and after hematopoietic stem cell transplantation. Bone Marrow Transplant 26(2):187–192. doi:10.1038/sj.bmt.1702466 PubMedCrossRefGoogle Scholar
  34. 34.
    Wozakowska-Kaplon B, Opolski G, Janion M (2003) Atrial natriuretic peptide before and after cardioversion of persistent atrial fibrillation. Kardiol Pol 58(4):255–263PubMedGoogle Scholar
  35. 35.
    Ohta Y, Shimada T, Yoshitomi H, Inoue S, Murakami Y, Shimizu H, Nakamura K, Ohta T, Katoh H, Ishibashi Y (2001) Drop in plasma brain natriuretic peptide levels after successful direct current cardioversion in chronic atrial fibrillation. Can J Cardiol 17(4):415–420PubMedGoogle Scholar
  36. 36.
    Roziakova L, Bojtarova E, Mistrik M, Krajcovicova I, Mladosievicova B (2012) Abnormal cardiomarkers in leukemia patients treated with allogeneic hematopoietic stem cell transplantation. Bratisl Lek List 113(3):159–162Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Peter S. Haas
    • 1
  • Gabriele Ihorst
    • 2
  • Susanne Schnitzler
    • 1
  • Ralph Wäsch
    • 1
  • Reinhard Marks
    • 1
  • Hartmut Bertz
    • 1
  • Roland Mertelsmann
    • 1
  • Jürgen Finke
    • 1
  • Barbara Deschler
    • 1
  1. 1.Department of Hematology and OncologyFreiburg University Medical CenterFreiburgGermany
  2. 2.Clinical Trials UnitFreiburg University Medical CenterFreiburgGermany

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