Autologous Peripheral Blood Stem Cell Transplantation (PBSCT) in Malignant Lymphoma: Prospective Single Center Analysis on Cardiac Assessment with B-Type Natriuretic Peptide (BNP).
Authors: Müller Antonia M.S. , Dierks Christine , Finke Jurgen , Engelhardt Monika 
Published: October 2019

Abstract
The efficacy of first-line intensive chemotherapy (CX) with PBSCT and its use as subsequent treatment in relapsed lymphoma patients (pts) was analysed in the past. According to the International Prognostic Index (IPI), first-line auto-PBSCT was shown to be superior to standard-CHOP with intermediate- or high-risk lymphoma pts as well as pts with relapse. This suggests that CHOP alone can no longer be regarded as standard treatment for these pts. However, with increasing curative prospects also for older pts, CX-induced cardiotoxicity (CT), eventually leading to acute or chronic heart failure (HF), becomes a relevant factor on morbidity and mortality. The incidence of clinically manifest CT in pts undergoing PBSCT has been estimated between 5–10%. However, in the presence of multiple complex medical problems with several co-existing pathologies, it is often difficult to diagnose HF. BNP is a hormone mostly secreted from the heart ventricles which has recently gained popularity for the following reasons: It is 1. related to HF severity and clinical status, 2. increased as left ventricular function deteriorates due to wall stretch and tension, 3. strongly associated with prognosis across the whole spectrum of HF and 4. a powerful independent predictor of mortality and morbidity in the long-term follow-up of HF cohorts. Here, we determined cardiac markers in malignant lymphoma pts to determine PBSCT-induced CT. For cardiac assessment, BNP and Troponin T (TrT) concentrations were measured before (day [d]0) and after PBSCT (d30, 3months [m], 1year [y]). Concomitant recordings of ECG, echocardiography and clinical history were carried out. So far, 39 consecutive pts (m:f=23:16) with a median age of 55 (19–70) y have been enrolled. 23 pts had high-grade NHL, 10 pts had indolent-NHL and 6 pts had Hodgkin’s disease. Most pts had stage III or IV disease (90%). Their median IPI was 4. First-line PBSCT vs. PBSCT following relapse was performed in 22 vs. 17 pts, respectively. All pts had received standard-dose CX prior to PBSCT. The used mobilization CX were VCP-E with first-line PBSCT or DHAP following relapse achieving CR, PR or SD prior to PBSCT in 10, 13 and 9 pts, respectively. All pts received high-dose CX with BEAM, retransfusing median CD34+ cells of 4.5x10e6/kg. Treatment related mortality was 0%. Currently, 35 pts are alive. Cardiac events (CE) occurring before PBSCT were coronary heart disease in 4 pts and prior myocardial infarction in 3 pts. After PBSCT, 10 pts without prior cardiac history developed mainly arrhythmias. BNP proofed to be a significantly more sensitive marker than TrT, showing elevated levels in 69% of pts at any time post PBSCT. In comparison, TrT was never elevated. Median BNP levels on d0, d30, 3m, and 1y after PBSCT were 142, 224, 228 and 207pg/ml (normal <125pg/ml), respectively, with highest increases on d30 and 3m after PBSCT. Significantly higher BNP levels were observed in pts with CE (224pg/ml) compared to those without (125pg/ml; p=0.027), and in pts >55y (228pg/ml) compared to pts <55y (144pg/ml; p=0.023). Taken together, this ongoing analysis demonstrates that PBSCT is well tolerated and shows promising responses in high-risk and relapsed lymphoma pts, who would have a poor prognosis with standard CHOP. Although not suitable as sole diagnostic evidence, elevated BNP levels seem to be of value before and after PBSCT as a simple, sensitive and specific predictor of impaired cardiac function and may be useful in monitoring pts undergoing high-dose CX.