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.

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...

The most common means of mobilizing autologous stem cells is G-CSF alone or combined with cyclophosphamide (CY) to obtain sufficient CD34+ cells for one to two transplants. There are few prospective, randomized studies investigating mobilization regimens in multiple myeloma (MM), especially after lenalidomide-based induction. We designed this prospective, randomized study to compare low-dose CY 2 g/m2+G-CSF (arm A) and G-CSF alone (arm B) after lenalidomide-based up-front induction in MM. Of the 80 initially randomized patients, 69 patients were evaluable, 34 and 35 patients in arms A and B, respectively. The primary end point was the proportion of patients achieving a yield of ⩾3 × 106/kg CD34+ cells with 1−2 aphereses, which was achieved in 94% and 77% in arms A and B, respectively (P=0.084). The median number of aphereses needed to reach the yield of ⩾3 × 106/kg was lower in arm A than in arm B (1 vs 2, P=0.035). Two patients needed plerixafor in arm A and five patients in arm B (P=0.428). Although CY-based mobilization was more effective, G-CSF alone was successful in a great majority of patients to reach the defined collection target after three cycles of lenalidomide-based induction.

Mobilized peripheral blood (PB) is the preferred source of stem cells (PBSCs) for autologous stem cell transplantation (ASCT). The use of cytokines, alone or in combination with chemotherapy (chemomobilization), is currently the most common strategy applied to collect PBSCs. However, a significant proportion of patients with lymphoid malignancies fail to mobilize enough PBSCs to proceed to ASCT. Plerixafor has been recently introduced for clinical use to enhance PBSC mobilization and has been shown to be more effective than granulocyte-colony-stimulating factor (G-CSF) alone in patients with multiple myeloma or non-Hodgkin's lymphoma. There is limited experience on combining plerixafor with chemotherapy plus G-CSF in patients who mobilize poorly. This review attempts to summarize the published experience on the preemptive use of plerixafor after chemomobilization or G-CSF mobilization to enhance stem cell collection and to prevent mobilization failure. Current evidence suggests that addition of plerixafor is safe and effective in the large majority of the patients with low blood CD34+ cell counts after mobilization and/or poor yield after the first collection(s). Circulating CD34+ cell counts can be increased by severalfold with plerixafor and the majority of the patients considered difficult to mobilize can be successfully collected. Although more studies are needed to evaluate proper patient selection and optimal timing for the addition of plerixafor after chemotherapy, its mechanism of action inducing the rapid release of CD34+ cells from the marrow to the PB makes this molecule suitable for its "preemptive" use in patients who are difficult to mobilize.