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E Jantunen

Publications and source records attributed to E Jantunen.

At least 37 records · Page 2Linked to original sources
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

Radiologically guided fine needle lung biopsies in the evaluation of focal pulmonary lesions in allogeneic stem cell transplant recipients.

Lung problems are common in allogeneic stem cell transplant (SCT) recipients. To evaluate the feasibility and diagnostic yield of radiologically guided fine needle lung biopsy (FNLB) in allogeneic SCT recipients with focal pulmonary lesions, a retrospective analysis was carried out. Between 1989 and 1998, radiologists performed a total of 30 FNLBs in 21 allogeneic SCT recipients, guided either by ultrasound (n = 17) or computed tomography (n = 13). The median time from SCT to the first FNLB was 131 days (20-343 days). Prophylactic platelet transfusions were given in 19 procedures (66%). The complications of FNLB included clinically insignificant pneumothorax in four procedures (13%) and self-limiting haemoptysis in one case (3%). The first FNLB was suggestive of invasive pulmonary aspergillosis (IPA) in five patients (24%). Additional clinically useful findings of FNLB included Pseudomonas (two patients) and Nocardia (one patient). The final diagnosis of pulmonary lesions was IPA in 14 patients, immunological lung problems in four patients and other in three patients. Radiologically guided FNLB is feasible in allogeneic SCT recipients and has a low complication rate. The diagnostic yield is high especially for IPA.

Adolescent↗
PubMed2002

Aspergillus infections in allogeneic stem cell transplant recipients: have we made any progress?

Invasive aspergillosis (IA) is common in allogeneic SCT recipients, with an incidence of 4-10%. The majority of these infections are diagnosed several months after SCT and they are frequently associated with GVHD. The diagnosis is difficult and often delayed. Established IA is notoriously difficult to treat with a death rate of 80-90%. This review summarises recent data on this problem to assess whether there has been any progress. Effective prophylactic measures are still lacking. Severe immunosuppression is the main obstacle to the success of therapy. Recent and ongoing developments in diagnostic measures and new antifungal agents may improve treatment results to some extent, but Aspergillus infections still remain a formidable problem in allogeneic transplantation. Further studies in this field will focus on the role of various cytokines and combinations of antifungal agents.

Antifungal Agents↗
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

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↗
PubMed2000

Stem cell transplantation for treatment of severe autoimmune diseases: current status and future perspectives.

Autoimmune diseases include a heterogeneous group of disorders with variable presentation and severity. Immunosuppressive and immunomodulatory therapies are often used for treatment with considerable success in some cases. These diseases may also be severe and refractory to conventional treatment. Thus more aggressive intervention might be indicated in a subset of patients. Animal studies suggest that high-dose therapy supported by stem cell transplantation may lead to remissions in experimental autoimmune disease models. Anecdotal case reports suggest that the same may be the case in some human autoimmune diseases as well. This review attempts to summarise some current concepts and future perspectives on stem cell transplantation in the treatment of severe autoimmune diseases.

Acute Disease↗
PubMed2000

Diagnostic aspects of invasive Aspergillus infections in allogeneic BMT recipients.

To investigate diagnostic aspects of invasive aspergillosis (IA) in allogeneic BMT recipients, the charts of 22 consecutive patients with IA transplanted in 1989-1995 were reviewed. IA was diagnosed 69-466 days (median 131 days) post BMT. In 16 patients (73%), a definite or probable diagnosis of IA was made during life. Respiratory symptoms were the presenting feature in half of the patients followed by neurological symptoms (27%). Chest X-ray revealed single or multiple nodular lesions in 10 patients; cavitation was observed in five patients. Tissue biopsy was the most common method of diagnosis (nine patients: lungs 6, liver 1, subcutaneous tissue 1, brain 1). Five IA cases were detected by nine guided fine needle lung biopsies in eight patients and without complications. Bronchoalveolar lavage was performed in 14 patients with findings suggestive of invasive pulmonary aspergillosis in eight cases. Lungs were the most common organ affected (90%) followed by central nervous system (41%). The diagnosis of IA is still difficult, and a large number of patients have advanced infection at diagnosis. Methods for early diagnosis are needed. Patients with a clinical suspicion of IA should be treated vigorously with antifungal agents during the diagnostic work-up.

Adolescent↗
PubMed2000

Feasibility and toxicity of high-dose chemotherapy supported by peripheral blood stem cell transplantation in elderly patients (>/=60 years) with non-Hodgkin's lymphoma: comparison with patients <60 years treated within the same protocol.

Limited data are available concerning feasibility and toxicity of progenitor cell mobilization and high-dose therapy (HDT) supported by peripheral blood stem cell transplantation (PBSCT) in elderly patients (>/=60 years) with non-Hodgkin's lymphoma (NHL). From 1995 to 1999, 17 elderly NHL patients (median age 63 years, range 60-70) entered our HDT program and were mobilized with CY (4 g/m2) followed by G-CSF. Mobilization was successful in 13 patients, who then received BEAM or BEAC followed by PBSCT. The feasibility and toxicity of progenitor cell mobilization and HDT in the elderly patients were compared with experiences in 62 NHL patients <60 years (median 46 years, range 16-59), who received the same mobilization protocol and of whom 48 patients received HDT supported by PBSCT. No significant differences were observed between these groups in the success rate of progenitor cell mobilization, in the number of CD34-positive cells collected or in the number of aphereses needed. HDT appeared to be somewhat more toxic in the elderly patients: a higher peak CRP value (P = 0.08) and longer in-hospital stay (P = 0. 05) were observed. No differences were found in transplant-related mortality or severe organ toxicity between these age groups except for oral mucositis grade >2, which tended to be more common in the elderly patients (P = 0.07). We conclude that progenitor cell mobilization and HDT supported by PBSCT is also feasible in selected elderly patients with NHL. Bone Marrow Transplantation (2000) 26, 737-741.

Adolescent↗