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Thirty adult patients v non-Hodgkin"s lymphoma to be studied zu evaluate prospectively the significance des early decline bei left ventricular ejection fraction after low cumulative doxorubicin sheep (200 mg m−2) in predicting the danach impairment des left ventricular function. Cardiac function was monitored v radionuclide ventriculography weist baseline and after cumulative doxorubicin doses des 200, 400 and 500 mg m−2. Cardiotoxicity was defined together a decrease bei left ventricular ejection fraction of more 보다 10% units kommen sie a final left ventricular ejection portion ⩽50%. Twenty-eight patients received doxorubicin ⩾400 mg m−2 und were evaluable weil das cardiotoxicity. Clinical heart fail developed an two patients (7%) ~ a cumulative doxorubicin dose des 500 mg m−2. Left ventricular ejection fraction decreased much more than 10% absolute ejection portion units kommen sie a final left ventricular ejection portion ⩽50% in 10 patient (36%). Left ventricular ejection portion decreased indigenous 56±1.5% kommen sie 53.6±1.5% (P=0.016) an patients v no cardiotoxicity, and from 60.8±2.4% to 41.8±2.0% (P−2 was highly far-ranging (left ventricular ejection portion 49.7±1.8%, P=0.001 mit baseline). Bei receiver operator characteristic analysis, die area under the curve for the decrease in left ventricular ejection fraction weist a cumulative doxorubicin dose des 200 mg m−2 for predicting cardiotoxicity bei all patients was 0.858. Ns decrease in left ventricular ejection fraction von more 보다 4% systems after a cumulative doxorubicin dose of 200 mg m−2 had a 90% sensitivity und 72% specificity for predicting danach cardiotoxicity. Our results show that the significant impairment of left ventricular duty during doxorubicin therapy can be predicted early, already punkt low cumulative doxorubicin doses. This finding might be of value in identifying patients at high or short risk zum the development von anthracycline cardiotoxicity.

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Doxorubicin zu sein one von the most potent anti-neoplastic agents bei the treatment von lymphoid malignancies und many hard tumours. However, that is therapeutic value is limited über cumulative dose-related cardiotoxicity. Die incidence von congestive heart failure (CHF) throughout doxorubicin treatment has been reported to be 3% at a dose des 400 mg m−2 und 7% punkt a dose von 550 mg m−2 (von Hoff et al, 1979), but die occurrence von CHF zu sein unpredictable. Attempts zu prevent CHF encompass empiric dose limitation and serial assessment von left ventricular function. Only endomyocardial biopsy has actually been considered kommen sie be sensitive und specific enough bei predicting die development des CHF (Mason et al, 1978; Billingham and Bristow, 1984), but ns invasiveness and potential complications of the procedure limit its clinical use. Radionuclide ventriculography (RVG) has actually been concerned as ns best noninvasive method in identifying subclinical anthracycline cardiotoxicity in adult patients (Alexander et al, 1979; Schwartz et al, 1987; ziemlich et al, 1996). Guidelines based upon changes in systolic und diastolic left ventricular function oase been given for monitoring patient receiving anthracycline therapy (Alexander et al, 1979; Schwartz et al, 1987; durchaus et al, 1996).

Despite die introduction of neu imaging techniques like Indium-111-antimyosin (Carrio et al, 1995; Maini et al, 1997) und Iodine-123-metaiodobenzylguanidine (MIBG) scans (Valdés Olmos et al, 1995; Carrio et al, 1995) und serum markers des left ventricular dysfunction like natriuretic peptides (Bauch et al, 1992; Nousiainen et al, 1999; Meinardi et al, 2001) zum the monitoring des cardiac function during anthracycline therapy, none of these methods has been able kommen sie solve the problem of early detection des severe anthracycline-induced cardiotoxicity.

In die present examine we investigated ns significance von early impairment of cardiac systolic role after short cumulative doxorubicin sheep (200 mg m−2) und its ability kommen sie predict the later decrease in left ventricular ejection fraction (LVEF) during doxorubicin therapy.

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Thirty continually adult patient ⩽75 years of age with previously untreated non-Hodgkin"s lymphoma, who were scheduled zu receive CHOP chemotherapy, to be studied. Ns patients were regarded as eligible weil das study entry if lock had notfall received front anthracycline treatment or radiation therapy kommen sie mediastinum. A history von heart fail was deshalb considered as an exclusion criterion. Two patients passed away early during die treatment due to progressive lymphoma and were not evaluable. Thus, ns final study population consisted of 28 patients (17 men und 11 women) through a median age of 53 years (range 22–75 years). Six patients (21%) to be ⩾65 years. Six patients (21%) had a pre-existing cardiovascular condition (four patients had actually WHO klasse II hypertension, one geduldig had endured from a prior myocardial infarction and one patient from recurrent episodes des atrial fibrillation). Of the patients v a prior cardiovascular disease, 2 patients were end 65 years von age.

Approval for the study was obtained from the local moral committee and the patients noted written informed consent.


The CHOP chemotherapy was administered in standard sheep (cyclophosphamide, 750, doxorubicin, 50 and vincristine 1.4 mg m−2 were provided intravenously on work 1 und prednisolone 100 mg orally on work 1–5). Doxorubicin was given together a 30 min infusion. Ns cycle was repeated every 3 weeks to a total of 10 cycles. Doxorubicin was discontinued if left ventricular ejection fraction (LVEF) decreased below 45% (Druck et al, 1984; ziemlich et al, 1996). No radiotherapy was given during die study period.

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Radionuclide ventriculography

Radionuclide ventriculography (RVG) was performed at baseline and after a accumulation doxorubicin dose des 200, 400 and 500 mg m−2. Left ventricular ejection fraction (LVEF) was assessed utilizing standard techniques (Wackers et al, 1979). The equilibrium RVG was performed v semi bei vitro technetium-99m-labelled blood cell (injected activity 670 MBq). A big field-of-view gamma camera equipped with a high-sensitivity parallel feet collimator was used zum imaging. Ns cardiac cycle was divided right into 24 bilderrahmen with a 10% tolerance. Ten million counts to be acquired. Charme were analysed v a advertisement cardiac software (MGQ, atom Diagnostics Ab, Hägersten, Sweden). If ns LVEF decreased more than 10% units or was 10% units to in final LVEF ⩽50% was used together a cut-off point in the analyses together indicative von doxorubicin-induced cardiotoxicity (CT) (Schwartz et al, 1987).

Statistical methods

All calculations were performed with SPSS/PC statistical routine (version 9.0, SPSS Inc., chicago IL, USA). Ns differences zum continuous variables in time were analysed using basic linear model zum repeated measures. Paired, two tailed t-tests were applied zum post-hoc analyses. Added subgroup analyses for patients with und without left ventricular dysfunction as characterized on the basis of a decrease in LVEF to be performed using Mann–Whitney U-test for continuous variables und with Chi-Square test zum nominal data. Receiver operator characteristic evaluation (ROC) was used zu evaluate die diagnostic ability des the decrease in LVEF ~ a cumulative doxorubicin dose des 200 mg m−2 to predict die development von doxorubicin-induced cardiotoxicity (CT). A P-value