Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation

Abstract

Primary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NTproBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively.Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT. (Blood.

Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis

“…Their use has been validated in patients treated with conventional 23,36-38 and high-dose chemotherapy. 36,39 In the 2010 consensus analyses, biomarker criteria for clinical cardiac response and progression after initial therapy have been validated in newly diagnosed patients as shown in Figure 2. This approach is a major achievement in the scoring of cardiac responses, considering that these biomarkers are easily available in all clinical chemistry laboratories and that they are well standardized worldwide.…”

Current status of hematopoietic cell transplantation in the treatment of systemic amyloid light-chain amyloidosis

“…35 Currently, the cardiac biomarkers have an important role in deciding whether HDM will be recommended to the patient. 3 In most of the patients HDM will be performed as first-line therapy.…”

“…The most important determinant of clinical outcome (among various prognostic factors, Table 1) is the extent of cardiac involvement, 2 which can be sensitively and reliably measured using the cardiac biomarkers cardiac troponin T and N-terminal prohormone of brain natriuretic peptide. 3,4 Evaluation of the amount of the involved (amyloidogenic)-free light chain (iFLC) in the serum is a very useful tool for the assessment of the underlying monoclonal gammopathy. The iFLC concentration reflects the expansion of the aberrant clone and to some extent the severity of organ involvement.…”

Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement

“…With high-dose melphalan and auto-SCT (HDM/SCT), the median survival in stage III was only 8.4 months, but was not reached for stage I or II at 20 month follow-up. 3 Recently, serum free light chain (FLC) levels were incorporated and patients were assigned to four stages, with a 4-year estimated survival ranging from 87 to 46% months in stage I and stage IV, respectively, in HDM/SCT. 4 Finally, high-sensitivity TnT is another important baseline prognostic marker, predicting a short median survival for patients with levels above 77 ng/L.…”