Cardiac effects within 3 months of BEAC high-dose therapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation.
OBJECTIVE
Limited data are available on the cardiac effects of high-dose cyclophosphamide (CY) in patients with non-Hodgkin's lymphoma (NHL). We prospectively assessed the cardiac effects of high-dose CY in 30 adult NHL patients receiving CY 6 g/m(2) as part of BEAC high-dose therapy (HDT).


METHODS
Radionuclide ventriculography (RVG) and plasma natriuretic peptide (NT-proANP, NT-proBNP) measurements were performed simultaneously prior to BEAC at baseline (d - 7), 12 days (d + 12) and 3 months (m + 3) after stem cell infusion (D0). In addition to these time points, natriuretic peptides were measured 2 days before (d - 2) and 1 week (d + 7) after stem cell infusion.


RESULTS
Left ventricular ejection fraction (LVEF) decreased from d - 7 (53% +/- 2%) to d + 12 (49% +/- 2%, P = 0.009). However, no significant change in cardiac diastolic function was observed. The LVEF returned towards baseline by m + 3. Plasma NT-proANP and NT-proBNP increased significantly from baseline (445 +/- 65 pmol/L and 129 +/- 33 pmol/L) to d - 2 (1,127 +/- 142 pmol/L, P < 0.001 and 624 +/- 148 pmol/L, P < 0.001, respectively). Thereafter, they started to decrease, but on d + 7 NT-proANP (404 +/- 157 pmol/L, P = 0.048) and NT-proBNP (648 +/- 125 pmol/L, P = 0.015) were still significantly higher than at baseline. On d + 12 and m + 3 they no longer differed from baseline.


CONCLUSIONS
Our findings suggest that high-dose CY results in acute, subclinical systolic dysfunction in NHL patients previously treated with anthracyclines. Natriuretic peptides seem to be more sensitive than LVEF to reflect this transient cardiac effect. Serial measurements of natriuretic peptides might be a useful tool to assess cardiac effects of high-dose CY.
Kuittinen
T
T
Department of Medicine, Kuopio University Hospital, Kuopio, Finland. taru.kuittinen@kuh.fi
Jantunen
E
E
Vanninen
E
E
Mussalo
H
H
Vuolteenaho
O
O
Ala-Kopsala
M
M
Nousiainen
T
T
Hartikainen
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D015637:Gated Blood-Pool Imaging; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D036102:Peripheral Blood Stem Cell Transplantation; D011183:Postoperative Complications / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D011184:Postoperative Period; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012680:Sensitivity and Specificity; D013318:Stroke Volume; D013599:Systole; D014182:Transplantation, Autologous; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology
D015415:Biomarkers; C099254:N-terminal proatrial natriuretic peptide; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); D003561:Cytarabine; D020097:Natriuretic Peptide, Brain; D005047:Etoposide; D009320:Atrial Natriuretic Factor; D003520:Cyclophosphamide; D002330:Carmustine