Summary: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 þ 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 ¼ 0.001) or prior to mobilisation (P ¼ 0.001) and low platelet count just prior to mobilisation (P ¼ 0.001). In multivariate analysis, only BM involvement at diagnosis (P ¼ 0.004) and platelet count just prior to mobilisation (P ¼ 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.

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 m 72 ) 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 m 72 . Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10% units to a final left ventricular ejection fraction 450%. Twenty-eight patients received doxorubicin 5400 mg m 72 and were evaluable for cardiotoxicity. Clinical heart failure developed in two patients (7%) after a cumulative doxorubicin dose of 500 mg m 72 . Left ventricular ejection fraction decreased more than 10% absolute ejection fraction units to a final left ventricular ejection fraction 450% 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% (P50.001) 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 m 72 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 m 72 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 m 72 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.

Limited information is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients 465 years of age. In 1995-2005, 22 myeloma patients X65 years (median 68, eight X70) and 79 patients o65 years (median 57) were included in an identical treatment protocol. The first progenitor cell mobilization with cyclophosphamide plus granulocyte-colony stimulating factor (G-CSF) was successful in 95 and 96% of the patients, respectively. To date, 92 patients have received MEL (melphalan) 200 mg/m 2 supported by ASCT. No early treatmentrelated deaths were observed among 22 elderly patients, whereas one younger patient died early. Engraftment and the need for supportive care were comparable between groups. The elderly patients tended to have more WHO grade 3-4 oral or gastrointestinal toxicity when compared to the younger patients (45 vs 23%, P ¼ 0.06). After ASCT, a complete response was observed in 44% of the elderly patients and 36% of the younger patients, respectively. No difference was observed between these age groups in progression-free survival (23 vs 21 months) or overall survival (57 vs 66 months) after ASCT. We conclude that MEL200 is a safe and efficacious treatment in selected elderly myeloma patients.

Abstract. Nousiainen T, Vanninen E, Jantunen E, Puustinen J, Remes J, Rantala A, Vuolteenaho O, Hartikainen J (Kuopio University Hospital, Kuopio; Satakunta Central Hospital, Pori; University of Oulu, Oulu, Finland). Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction. J Intern Med 2002; 251: 228-234.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 nonHodgkin'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 ¼ 0.036) and fractional shortening (FS) from 34.6 ± 1.4 to 27.8 ± 0.9% (P ¼ 0.002). Peak E wave velocity decreased from 63.3 ± 3.2 to 51.3 ± 2.6 cm s )1 (P ¼ 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 ¼ 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 ¼ 0.002), NT-pro-ANP from 288 ± 22 to 380 ± 42 pmol L )1 (P ¼ 0.019) and BNP from 3.3 ± 0.4 to 8.5 ± 2.0 pmol L )1 (P ¼ 0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NTpro-ANP (r ¼ )0.524, P ¼ 0.018) and plasma BNP (r ¼ 0.462, P ¼ 0.04) and between the decrease in PFR and the increases in plasma ANP (r ¼ )0.457, P ¼ 0.043) and plasma NT-pro-ANP (r ¼ )0.478, P ¼ 0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r ¼ )0.535, P ¼ 0.008), between E/A ratio and plasma NT-pro-ANP (r ¼ )0.432, P ¼ 0.04) and between E/A ratio and plasma BNP (r ¼ )0.557, P ¼ 0.006) as well as between 1/3FF and plasma BNP (r ¼ )0.493, P ¼ 0.017). There was also a trend for correlation between LA diameter and plasma BNP (r ¼ 0.395, P ¼ 0.062) and peak E wave velocity and plasma BNP (r ¼ )0.414, P ¼ 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 doxorubicininduced LV dysfunction the secretion of nat...

Summary: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 VAD7local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m 2 ) (n ¼ 25) or intermediate-dose CY (ID-CY, 4 g/m 2 ) (n ¼ 32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 Â 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, Po0.001), lower frequency of fever (20 vs 73%, Po0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P ¼ 0.004) and days on parenteral antibiotics (0 vs 4 days, Po0.001). 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. Bone Marrow Transplantation (2003) 31, 347-351. doi:10.1038/sj.bmt.1703840 Keywords: cyclophosphamide; progenitor cell mobilisation; efficiency; toxicity; multiple myeloma Patients with multiple myeloma (MM) have a median survival of 3-4 years with conventional chemotherapy. In a randomised trial, high-dose therapy supported by stem cell rescue was superior over conventional chemotherapy in terms of complete remission rate, progression-free survival and overall survival. 1 The superiority of single or tandem autotransplants over conventional therapy has also been suggested in some controlled studies. 2,3 More than 95% of autotransplants for MM are now performed with the support of blood progenitor cells. 4 High-dose (7 g/m 2 ) cyclophosphamide (CY) alone or combined with a growth factor was initially used for mobilisation of progenitor cells in myeloma patients. [5][6][7] Goldschmidt et al 8 found that CY 7 g/m 2 plus G-CSF was superior to CY 4 g/m 2 plus G-CSF in this regard. However, high-dose CY is associated with significant toxicity. 7,9 Recently, Fitoussi et al 9 showed that intermediate-dose CY (ID-CY) (4 g/m 2 ) plus growth factor was equally effective as high-dose CY in mobilising progenitor cells in myeloma patients but was less toxic.Mobilisation with CY 4 g/m 2 plus G-CSF is, however, also associated with significant toxicity and need for supportive care. We hypothesised whether low-dose CY (LD-CY) (up to 2 g/m 2 ) could be as effective and, less toxic mobilisation regimen in patients with newly diagnosed MM. Therefore, a retrospective analysis in myeloma patients previously...

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The objective of this study was to evaluate etiology and consequences of neutropenic fever in AML patients. Two hundred and ninety neutropenic periods following chemotherapy in 84 AML patients were retrospectively evaluated. Neutropenic fever was found in 280 periods (97%). Severe sepsis developed in 35 occasions (13%) and 9 patients (11%) died due to severe sepsis. In 165 episodes with neutropenic fever (59%), the potential causative organism was found in blood cultures. Gram-negative bacteria were more commonly found in patients who developed severe sepsis (40% vs. 23%, p = 0.03). CRP after 2 - 3 days from start with fever was higher in patients with severe sepsis (190 mg/L vs. 96 mg/L, p < 0.001) but the rise in CRP rather coincided than preceded with the development of severe sepsis. Severe sepsis is associated with significant mortality in AML patients. Earlier methods than CRP are needed to predict development of severe sepsis.

Summary: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 1990Finland during -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 ¼ 22) or BEAM (N ¼ 15), supported by blood stem cells in 34 patients (92%). Early transplantrelated 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 ¼ 0.007). OS at 5 years was 63% in patients transplanted in CR/PR1 vs 45% in those transplanted in other disease status (P ¼ NS). Prospective studies are needed to define the role of ASCT in this lymphoma type.