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T Nousiainen

Publications and source records attributed to T Nousiainen.

At least 19 recordsLinked to original sources
PubMed2004

Autologous stem cell transplantation in adult patients with peripheral T-cell lymphoma: a nation-wide survey.

Limited experience is available on the feasibility and efficacy of high-dose therapy (HDT) supported by autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL). Therefore, a nation-wide survey was conducted in adult patients transplanted for PTCL in Finland during 1990-2001. After histopathology review, 37 patients were identified. The median age was 46 years (16-68) at the time of ASCT. Histology included PTCL not otherwise specified in 14 patients, anaplastic large cell lymphoma (ALCL) in 14 patients, and other in nine patients. Disease status at the time of ASCT was CR/PR1 in 18 patients; CR/PR2 in 14 patients, and other in five patients. HDT consisted of either BEAC (N=22) or BEAM (N=15), supported by blood stem cells in 34 patients (92%). Early transplant-related mortality was 11%. With a median follow-up of 24 months from HDT, 16 patients (43%) have relapsed or progressed. The estimated 5-year overall survival (OS) was 54%. Patients with ALCL had superior OS when compared with other subtypes (85 vs 35%, P=0.007). OS at 5 years was 63% in patients transplanted in CR/PR1 vs 45% in those transplanted in other disease status (P=NS). Prospective studies are needed to define the role of ASCT in this lymphoma type.

Adolescent↗
PubMed2004

Prediction of mobilisation failure in patients with non-Hodgkin's lymphoma.

Factors affecting progenitor cell mobilisation in patients with non-Hodgkin's lymphoma (NHL) are incompletely understood. We have analysed factors predicting mobilisation failure in 97 consecutive patients with NHL (59 males, 38 females; median age 49 years) who received mobilisation with intermediate-dose CY (4 g/m(2)) followed by G-CSF. The histology included large cell B (N=50), mantle cell (N=16), follicular (N=16) and other NHL (N=15). The disease status was 1CR/PR/primary refractory in 66 patients and >1 CR/PR in 31 patients. The minimum criterion for successful mobilisation was the collection of >or=1.5 x 10(6)/kg CD34(+) cells. In all, 18 patients (19%) failed to reach this threshold. In univariate analysis, premobilisation factors associated with mobilisation failure included BM involvement at the time of diagnosis (P=0.001) or prior to mobilisation (P=0.001) and low platelet count just prior to mobilisation (P=0.001). In multivariate analysis, only BM involvement at diagnosis (P=0.004) and platelet count just prior to mobilisation (P=0.01) were associated with mobilisation failure. A mathematical model based on these two factors and presented in the form of a receiver operating characteristics curve showed a sensitivity of 0.71 and a specificity of 0.77 in the prediction of mobilisation failure. Patients at a high risk of mobilisation failure may benefit from novel approaches.

Adolescent↗
PubMed2004

Oral treatment of acute myeloid leukaemia with etoposide, thioguanine, and idarubicin (ETI) in elderly patients: a prospective randomised comparison with intravenous cytarabine, idarubicin, and thioguanine in the second and third treatment cycle.

A randomised multicentre study was conducted among patients over 65 yr of age with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with etoposide 80 mg/m(2) and thioguanine 100 mg/m(2) twice daily on 5 d and idarubicin 15 mg/m(2) on 3 d (ETI) to a mainly i.v. combination of cytarabine 100 mg/m(2) twice daily on 5 d, idarubicin 12 mg/m(2) x 1, and thioguanine (TAI). Ninety-two patients were enrolled. Their median age was 72 yr, range 65-84 yr. Sixty-five patients had de novo AML, 21 AML subsequent to myelodysplastic syndrome, and six treatment-related AML. They received at first a 6-d i.v. treatment with cytarabine and idarubicin. After the first treatment, 68 patients were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients, 52 (57%) achieved remission at some stage. The median survival was 10 months. There were no significant differences between the patients randomised to ETI or TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation in both arms), event-free survival or relapse rate. The patients randomised to receive ETI spent significantly fewer days at hospital during the two randomised cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter neutropenias and thrombocytopenias and fewer and less severe infections. In conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as obtained with mainly i.v. TAI, with less toxicity and reduced need for hospitalisation.

Administration, Oral↗
PubMed2004

Invasive fungal infections in autologous stem cell transplant recipients: a nation-wide study of 1188 transplanted patients.

UNLABELLED: Based on small single-centre series, the risk of invasive fungal infections (IFI) has been considered small in autologous stem cell transplant (ASCT) recipients. PURPOSE: To analyse epidemiological and clinical features of (IFI) among ASCT recipients in Finland 1990-2001. PATIENTS: During the study period, 1188 adult patients received high-dose therapy supported by ASCT in six centres. Altogether, 1112 patients (94%) received blood progenitor cells. The graft was CD34+ selected in 261 patients (22%). The major diagnostic groups were non-Hodgkin's lymphoma (n = 417), multiple myeloma (n = 395), breast cancer (n = 132) and Hodgkin's lymphoma (n = 53). RESULTS: Eighteen patients (1.5%) with IFI were identified. The incidence of proven or probable invasive aspergillosis was 0.8%, followed by candidaemia with an incidence of 0.3%. The median time to the diagnosis of IFI was 35 d (6-162) from the progenitor cell infusion. In fourteen patients (78%) IFI was diagnosed during lifetime and they were treated with antifungal therapy for a median of 50 d. Nine patients (64%) were cured. CONCLUSIONS: IFI appears to be a rare event after ASCT and Aspergillus infections seem to be predominant. These epidemiological features have an impact in planning prophylactic and empirical antifungal strategies in ASCT recipients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma.

Cyclophosphamide (CY) combined with granulocyte colony-stimulating factor (G-CSF) is commonly used to mobilise blood progenitor cells to support high-dose therapy in patients with multiple myeloma (MM). The optimal dose of CY in this setting is unknown. We have retrospectively analysed mobilisation efficiency and need for supportive care in 57 patients with newly diagnosed myeloma previously treated with VAD+/-local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m(2)) (n=25) or intermediate-dose CY (ID-CY, 4 g/m(2)) (n=32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 x 10(6)/kg CD34+ cells were collected from 88% and 84% of the patients with a single apheresis, respectively. Only one patient in the LD-CY group (4%) failed to mobilise vs none in the ID-CY group. Patients mobilised with LD-CY plus G-CSF had less toxicity: fewer hospital days during the mobilisation and apheresis procedures (5 vs 9 days, P<0.001), lower frequency of fever (20 vs 73%, P<0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P=0.004) and days on parenteral antibiotics (0 vs 4 days, P<0.001). While these regimens seem to be equally effective in terms of progenitor cell mobilisation in newly diagnosed patients with MM, LD-CY+G-CSF is preferential because of more optimal resource utilisation and more favourable toxicity profile.

Adult↗
PubMed2003

Is chemotherapy scoring useful to predict progenitor cell mobilisation in patients with non-Hodgkin's lymphoma?

About 10-30% of patients with non-Hodgkin's lymphoma (NHL) intended to receive high-dose therapy are difficult to mobilise. Damage to the stem cell pool caused by previous chemotherapy may be an important factor in predicting progenitor cell mobilisation. We have analysed associations between chemotherapy score and efficiency of progenitor cell mobilisation in 120 consecutive NHL patients mobilised with intermediate-dose cyclophosphamide (4 g/m(2)) plus G-CSF. The original chemotherapy scoring system proposed by Drake et al was applicable in only 27% of our patients and was not predictive for mobilisation outcome. Therefore we made an improved scoring system for previous chemotherapy by adding new drugs. Altogether, 111 patients (93%) could be scored. Our chemotherapy score showed an inverse correlation with the peak blood CD34(+) count measured after the mobilisation (r=-0.214, P=0.024) and with the number of CD34(+) cells collected (r=-0.234, P=0.02). However, in the receiver operating characteristics curve, no threshold value could be detected for chemotherapy score predicting mobilisation failure. Thus, both the original scoring system as well as our more widely applicable scoring system seem to be of limited value in predicting progenitor cell mobilisation in patients with NHL.

Adolescent↗
PubMed2003

Multiple complete remissions in a patient with acute myeloid leukemia (M4eo) with low-dose cytosine arabinoside and all-trans retinoic acid.

A 54-year-old female with acute myeloid leukemia (AML) (FAB M4eo) was treated at second relapse with a combination of low-dose cytosine arabinoside (LDAraC) (20 mg b.i.d. subcutaneously) and all-trans retinoic acid (ATRA) (45 mg/m2/d orally) on days 1-10. The patient achieved a complete hematological remission after the first cycle and was consolidated with three similar cycles at four-week intervals. Subsequently, the patient relapsed several times. Altogether seven complete hematological remissions including some cytogenetic remissions were induced with the same regimen. The patient survived 81 months after the start with LDAraC-ATRA regimen. This low-toxicity regimen may be useful in some patients with poor-risk AML.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

BEAC or BEAM for high-dose therapy in patients with non-Hodgkin's lymphoma? A single centre analysis on toxicity and efficacy.

High-dose chemotherapy supported by autologous stem cell transplantation is widely used in patients with non-Hodgkin's lymphoma (NHL). Limited data is available on the comparative toxicity and efficacy of various high-dose regimens applied in NHL. We therefore analysed regimen-related toxicity and outcome in 71 consecutive NHL patients who received either BEAC (N = 36) or BEAM (N = 35) supported by peripheral blood progenitor cell infusion plus granulocyte colony-stimulating factor. The patients who received BEAM had significantly more often WHO grade > 2 mucositis (63 vs. 28%, P = 0.009) and diarrhoea grade >2 (29 vs. 8%, P = 0.062). Septicaemia also tended to be more frequent and the peak CRP value was higher in the BEAM group (140 vs. 113 mg/l, P = 0.034). Transplant-related mortality (< 100 d) was 3 and 9% in the BEAC and BEAM groups, respectively. No significant differences were observed in overall survival or progression free survival between these two groups. While BEAC and BEAM appears to have equal antitumour efficacy in patients with NHL, BEAM seems to be more toxic to the gastrointestinal tract. However, randomised studies are needed for more definitive conclusions on the relative merits of various high-dose regimens in patients with NHL.

Adolescent↗
PubMed2002

Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients.

Thirty adult patients with non-Hodgkin's lymphoma were studied to evaluate prospectively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose (200 mg x m(-2)) in predicting the later impairment of left ventricular function. Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg x m(-2). Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10% units to a final left ventricular ejection fraction < or =50%. Twenty-eight patients received doxorubicin > or =400 mg x m(-2) and were evaluable for cardiotoxicity. Clinical heart failure developed in two patients (7%) after a cumulative doxorubicin dose of 500 mg m(-2). Left ventricular ejection fraction decreased more than 10% absolute ejection fraction units to a final left ventricular ejection fraction < or =50% in 10 patients (36%). Left ventricular ejection fraction decreased from 56+/-1.5% to 53.6+/-1.5% (P=0.016) in patients with no cardiotoxicity, and from 60.8+/-2.4% to 41.8+/-2.0% (P<0.001) in patients with cardiotoxicity. For patients who developed cardiotoxicity, the fall in left ventricular ejection fraction after a cumulative doxorubicin dose of only 200 mg x m(-2) was highly significant (left ventricular ejection fraction 49.7+/-1.8%, P=0.001 vs baseline). In receiver operator characteristic analysis, the area under the curve for the decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 200 mg x m(-2) for predicting cardiotoxicity in all patients was 0.858. The decrease in left ventricular ejection fraction of more than 4% units after a cumulative doxorubicin dose of 200 mg x m(-2) had a 90% sensitivity and 72% specificity for predicting later cardiotoxicity. Our results show that the significant impairment of left ventricular function during doxorubicin therapy can be predicted early, already at low cumulative doxorubicin doses. This finding may be of value in identifying patients at high or low risk for the development of anthracycline cardiotoxicity.

Adult↗
PubMed2002

Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction.

OBJECTIVES: To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO). DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels. CONCLUSIONS: The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.

Adult↗
PubMed2002

Recurrent Sphingomonas paucimobilis -bacteraemia associated with a multi-bacterial water-borne epidemic among neutropenic patients.

A cluster of septicaemias due to several water-related species occurred in a haematological unit of a university hospital. In recurrent septicaemias of a leukaemic patient caused by Sphingomonas paucimobilis, genotyping of the blood isolates by use of random amplified polymorphic DNA-analysis verified the presence of two distinct S. paucimobilis strains during two of the separate episodes. A strain of S. paucimobilis identical to one of the patient's was isolated from tap water collected in the haematological unit. Thus S. paucimobilis present in blood cultures was directly linked to bacterial colonization of the hospital water system. Heterogeneous finger-printing patterns among the clinical and environmental isolates indicated the distribution of a variety of S. paucimobilis clones in the hospital environment. This link also explained the multi-microbial nature of the outbreak.

Bacteremia↗
PubMed2002

A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients.

To evaluate feasibility and potential efficacy of amifostine (AMI) in the prevention of toxicities associated with high-dose melphalan (MEL), ten myeloma patients received AMI 910 mg/m2 in 15 min infusion preceding MEL 200 mg/m2 followed by stem cell infusion (AMI group). Hematologic and extra-hematologic toxicities as well as the need for supportive care observed in the AMI group were compared with ten myeloma patients treated in an identical protocol but without AMI. Hypotension was the most important adverse event of AMI infusion. No differences were observed in the time of engraftment between the AMI group and the control group neither was there any difference in the need for supportive care. Oral mucositis grade >2 was observed in 30% of the patients in both groups. Diarrhea grade >2 occurred only in two AMI patients but in five control patients. AMI preceding high-dose MEL is feasible, although adverse events are observed in some patients. Whether AMI could reduce the gastrointestinal toxicity associated with high-dose MEL can be reliably assessed only in prospective randomized trials.

Adult↗
PubMed2001

Anthracycline-induced cardiomyopathy: long-term effects on myocardial cell integrity, cardiac adrenergic innervation and fatty acid uptake.

Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemotherapy. Limited data is available on the physiological mechanisms responsible for anthracycline-induced heart failure or its recovery. We studied four patients with a history of severe anthracycline-induced heart failure manifested 2-116 months earlier by using radionuclide ventriculography for the measurement of left ventricular function, indium-111-antimyosin scintigraphy for the detection of myocardial cell injury and iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innervation. Myocardial perfusion and fatty acid utilization were assessed with iodine-123-paraphenyl pentadecanoid acid (pPPA) and single photon emission computed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had normal or near normal left ventricular ejection fraction (LVEF) (47 and 52%), whereas the patients with symptoms of heart failure had low ejection fractions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction tended to have higher antimyosin uptake suggesting more severe, persistent myocyte injury. All but one patient showed normal fatty acid utilization. These data suggest that patients with a history of severe anthracycline-induced cardiomyopathy have persistent myocardial cell injury and adrenergic dysfunction up to 10 years after the development of heart failure. These findings seem to be present regardless of recovery of left ventricular function.

3-Iodobenzylguanidine↗
PubMed2001

Comparison of echocardiography and radionuclide ventriculography in the follow-up of left ventricular systolic function in adult lymphoma patients during doxorubicin therapy.

OBJECTIVES: To compare echocardiography (ECHO) and radionuclide ventriculography (RVG) in the monitoring of left ventricular systolic function during doxorubicin therapy in adult lymphoma patients. DESIGN: Prospective study. SETTINGS: University hospital. SUBJECTS: A total of 28 adult patients who received doxorubicin to a cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: ECHO and RVG were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: At baseline, the mean (+/-SE) left ventricular ejection fractions (LVEF) were 58 +/- 1.3, 71 +/- 1.8 and 58 +/- 1.7% as determined by RVG, M-mode ECHO and two-dimensional (2D) ECHO, respectively. After the cumulative doxorubicin dose of 500 mg m(-2) LVEF decreased to 49.6 +/- 1.7% (RVG) (P < 0.001), 62 +/- 1.6% (M-mode) (P=0.006) and 52.5 +/- 1.3% (2D ECHO) (P=0.036). Although a significant correlation between LVEF determined by RVG and M-mode ECHO (r=0.615, P=0.002) and a trend between RVG and 2D ECHO (r=0.364, P=0.096) were observed, there were substantial differences in the results of individual patients. In the agreement analysis using the method of Bland and Altman there was a mean difference of 12% units with the upper limit of agreement +26% units and the lower limit of agreement -2.1% units for LVEF determinations with M-mode ECHO and RVG, and a mean difference of 3.3% units with upper and lower limits of agreement +19.6 and -13.1% units for LVEF determinations with 2D ECHO and RVG, respectively. CONCLUSION: We found only a moderate agreement between left ventricular systolic function determined by ECHO and RVG methods. Thus, in the follow-up of left ventricular function in adult patients during doxorubicin therapy, the guidelines based on LVEF measurement by RVG cannot be applied to ECHO. Consequently, RVG remains the method of choice in this context.

Adult↗
PubMed2001

Neuroendocrine changes during the evolution of doxorubicin-induced left ventricular dysfunction in adult lymphoma patients.

Doxorubicin-induced cardiotoxicity was used as a model to prospectively investigate neuroendocrine changes during the development of left ventricular dysfunction. Radionuclide ventriculography, frequency domain analysis of heart rate variability (HRV), and plasma noradrenaline and natriuretic peptide measurements were performed in 27 adult lymphoma patients at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m(2). The left ventricular ejection fraction (LVEF) decreased from 58.1+/-1.4% to 50.3+/-1.1% (P<0.001) and 49.3+/-1.7% (P<0.001) after cumulative doxorubicin doses of 400 and 500 mg/m(2) respectively. With a doxorubicin dose of up to 400 mg/m(2) there was an increase in sympathetic tone, characterized by a decrease in the normalized high-frequency (HF(nu)) power (P=0.011), and increases in the normalized low-frequency (LF(nu)) power (P=0.011), the LF/HF ratio (P=0.021) and the plasma noradrenaline concentration (P=0.034). The decrease in LVEF was correlated with the changes in LF(nu) and HF(nu) power (r=0.540, P=0.012) and LF/HF ratio (r=-0.452, P=0.04). However, after the cumulative doxorubicin dose of 500 mg/m(2) the changes in HRV components and plasma noradrenaline levels returned towards baseline. This was accompanied by increased concentrations of plasma atrial natriuretic peptide (P=0.004) and brain natriuretic peptide (P=0.021). Our findings suggest that doxorubicin-induced left ventricular dysfunction is associated with an early change in sympathovagal balance towards sympathetic predominance. Along with further progression of left ventricular dysfunction, there is an attenuation of sympathetic tone, which may be attributable to sympatho-adrenal inhibition by increased secretion of natriuretic peptides.

Adult↗