In long-term survivors of metastatic testicular cancer, we observed a significantly increased risk for occurrence of cardiac events accompanied by a persisting unfavorable cardiovascular risk profile. Accurate follow-up, focused on cardiovascular complications and aimed at intervention in these young cancer survivors, seems to be important.

High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) ( n = 17), or 4 × FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT ( n = 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to ( t 0 ), 5 months after ( t 1 ) and 9 months after chemotherapy ( t 2 ); these parameters were decreased at t 1 and t 2 compared to t 0 (high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t 1 . Paired individual leukocyte samples of t 0 and t 1 showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to –2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t 0 and t 1 . Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. © 2001 Cancer Research Campaign www.bjcancer.com

Objective-To investigate left ventricular dysfunction in patients who had been treated with anthracycline based chemotherapy. Methods-Autonomic function was compared with left ventricular diastolic function in 20 asymptomatic women with normal systolic function (left ventricular ejection fraction (LVEF) > 0.50) treated for breast cancer with high dose anthracycline based chemotherapy, and 20 age matched healthy controls. Left ventricular diastolic function was assessed echocardiographically by measuring the early peak flow velocity to atrial peak flow velocity ratio, isovolumic relaxation time, and deceleration time. Heart rate variability analysis was assessed for time domain and frequency domain parameters. Results-The mean (SD) age of the patients was 45 (7) years and the mean LVEF was 0.59 (0.06). The time interval after the end of chemotherapy was 29 (27) months. One or more diastolic variables were abnormal in 50% of the patients. Heart rate variability was abnormal in 85% of patients. Mean values of both time domain and frequency domain parameters were decreased (p < 0.05), in particular the parasympathetic indices. Conclusions-Autonomic impairment occurs in a large proportion of asymptomatic patients with normal systolic left ventricular function after high dose anthracycline based chemotherapy. In particular, heart rate variability analysis may be a sensitive tool to identify the first signs of cardiotoxicity in these patients.

Purpose: To determine whether granulocyte-macro phage colony-stimulating factor (GM-CSF) used in addi tion to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever.Patients and Methods: One hundred thirty-four pa tients with aliem atologic (n = 47) or solid tumor (n = 87) who had severe neutropenia {< 0.5 x 10 9/L) and fever (> 38.5°C once or > 38°C twice over a 12-hour observation period) w ere randomly assigned to receive GM-CSF 5 /u g /k g /d (n = 65) or placebo (n -69) in con junction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days* GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 109/L and temperature less than 37.5°C during 2 consecutive days, or for a leukocyte count > 1 0 x 1 09/lv both followed by a 24-hour observa tion period (hospitalization period).Results: Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 w ere 2.5 x 109/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 109/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with re gard to median number of days w ith less than 1.0 x 10 9/ L neutrophils (4 v 4 ) or days of fever {3 v3). The median number of days patients w ere hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range/ 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Q uality-of-life scores in 90 patients demon strated significant differences in favo r of the placebo group. Hospital costs w ere significantly higher for GM -CSF -treated patients if GM-CSF w as included in the price (median costs, $ 4 ,1 4 0 [US] for GM-CSF v $ 5 9 0 for p la cebo; P < .05).Conclusion: These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, a l though a significant effect of GM-CSF w as observed on neutrophil recovery.J Clin Oncol 1 4 :6 1 9 *6 2 7 , © 1 9 9 6 b y American So ciety o f Clinical Oncology. C HEMOTHERAPY-RELATED neutropenia and fever is a complication that occurs frequently during treatment of cancer patients. In particular, the severity and duration of neutropenia determines the risk of infec tion and the outcome of the patient.1, 2 Recently, different hematopoietic growth factors (HGFs) have been pro duced, which allows the opportunity to modulate the pe riod of granulocytopenia.Two options are available for applying HGFs after standard chemotherapy.3 First, HGF can be given as an adjunct to chemotherapy until recovery of peripheralblood counts is noted, in a number of studies, this policy has resulted in a 50% reduction of infectious complications,4,5 while in other studies, no significant effect has been shown with regard to the incidence of bacteremia, days of fever, or hospitalization duration.ü,; A second possibility would be to apply HGF only in the case of infection.8"n This approach woul...

Summary Sublines of the human small-cell lung carcinoma (SCLC) cell line GLC4 with acquired resistance to teniposide, amsacrine and mitoxantrone (GLC4/VM20 ,, GLC4/AM3, and GLC4/MIT60 ,, respectively) were derived to study the contribution of DNA topoisomerase Ila and -,B (Topolla and -,B) to resistance for Topolltargeting drugs. The cell lines did not overexpress P-glycoprotein or the multidrug resistance-associated protein but were cross-resistant to other TopoIl drugs. GLC4/VM20x showed a major decrease in Topolla protein (54%; for all assays presented in this paper the GLC4 level was defined to be 100%) without reduction in TopoII,B protein; GLC4/AM3X showed only a major decrease in TopoII,B protein (to 18%) and not in Topolla.In GLC4/MIT60 ,, the Topolla and -,B protein levels were both decreased (Topolla to 31%; TopoII,B protein was undetectable). The decrease in Topolla protein in GLC4/VM20 and GLC4/MIT60,,, was mediated by decreased Topollcx mRNA levels. Loss of Topolla gene copies contributed to the mRNA decrease in these cell lines. Only in the GLC4/MIT60x cell line was an accumulation defect observed for the drug against which the cell line was made resistant. In conclusion, Topollcx and -/3 levels were decreased differentially in the resistant cell lines, suggesting that resistance to these drugs may be mediated by a decrease in a specific isozyme.