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The experience sampling method is used to measure variance over time in events, moods, and behaviours in the work setting via palmtop computers in a sample of 41 employees. Theoretical propositions about event--mood--behaviour relations are derived from Affective Events Theory (Weiss & Cropanzano, 1996) and tested using within- and between-persons variance. The experiment found 56% of the variance in hedonic tone of mood was within- rather than between-persons. Hedonic tone was significantly related to both positive and negative work events in expected directions. The relationship between negative events and mood was approximately five times stronger than that between positive events and mood, even though positive events were reported three to five times more frequently than negative events. Hedonic tone was positively related to engaging in work withdrawal and negatively related to engaging in work tasks. Implications of these findings as well as the use of experience sampling for the study of dynamic workplace variables are discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: In multiple myeloma, combination chemotherapy with melphalan plus prednisone is still regarded as the standard of care in elderly patients. We assessed whether the addition of thalidomide to this combination, or reduced-intensity stem cell transplantation, would improve survival. METHODS: Between May 22, 2000, and Aug 8, 2005, 447 previously untreated patients with multiple myeloma, who were aged between 65 and 75 years, were randomly assigned to receive either melphalan and prednisone (MP; n=196), melphalan and prednisone plus thalidomide (MPT; n=125), or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 (MEL100; n=126). The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00367185. FINDINGS: After a median follow-up of 51.5 months (IQR 34.4-63.2), median overall survival times were 33.2 months (13.8-54.8) for MP, 51.6 months (26.6-not reached) for MPT, and 38.3 months (13.0-61.6) for MEL100. The MPT regimen was associated with a significantly better overall survival than was the MP regimen (hazard ratio 0.59, 95% CI 0.46-0.81, p=0.0006) or MEL100 regimen (0.69, 0.49-0.96, p=0.027). No difference was seen for MEL100 versus MP (0.86, 0.65-1.15, p=0.32). INTERPRETATION: The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should, at present, be the reference treatment for previously untreated elderly patients with multiple myeloma. [ABSTRACT FROM AUTHOR]

Background: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression- free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. Design: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (=1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. Results: The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the =1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. Conclusion: Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study. [ABSTRACT FROM AUTHOR]

Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myélome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months (P<0.001) and 1p32: 14.4 months vs 33.6 months (P<0.001); and overall survival (OS): 1p22: 44.2 months vs 96.8 months (P=0.002) and 1p32: 26.7 months vs 96.8 months (P<0.001). In multivariate analyses, 1p22 and 1p32 deletions still appear as independent negative prognostic factors for PFS and OS. In conclusion, our data show that 1p22 and 1p32 deletions are major negative prognostic factors for PFS and OS for patients with MM. We thus suggest that 1p32 deletion should be tested for all patients at diagnosis. [ABSTRACT FROM AUTHOR]

Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset of secondary genetic events that seem to reflect progression, 1q21 gain, NF-κB-activating mutations, RB1 and TP53 deletions, was examined. By using high-resolution single-nucleotide polymorphism arrays, subclones were identified with nonlinear complex evolutionary histories. Such reordering of the spectrum of genetic lesions, identified in a third of MM patients during therapy, is likely to reflect the selection of genetically distinct subclones, not initially competitive against the dominant population but which survived chemotherapy, thrived and acquired new anomalies. In addition, the emergence of minor subclones at relapse appeared to be significantly associated with bortezomib treatment. These data support the idea that new strategies for future clinical trials in MM should combine targeted therapy and subpopulations' control to eradicate all myeloma subclones in order to obtain long-term remission. [ABSTRACT FROM AUTHOR]

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years, and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including partial response in 69 (32%). The median overall survival and event-free survival from T0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. [ABSTRACT FROM AUTHOR]

For relapsed or refractory multiple myeloma (RRMM), a series of novel agents (thalidomide, bortezomib and lenalidomide) has emerged during the latest decade, but their use in routine clinical practice is not well documented as well as the cost of RRMM. Our aim is to review the therapeutic management of such patients in France and to estimate the associated costs. A retrospective cohort study, based on chart reviews, was conducted in French Haematology Departments over the period 2004-2007 and the associated direct costs estimated. One hundred and two patients with a relapse after first-line therapy were selected from five centres. The average follow-up from diagnosis or the date of first relapse to death or to the latest news was respectively 56·25 and 23·53 months. Novel agents were used in 73% of all cases, and in all cases of first relapse. Thalidomide and bortezomib were respectively the most frequently used second-line (57%) and third-line treatments (44%). The average number of lines of treatment received per patient as from first relapse was 2·75 (min 1; max 8) and the mean direct cost per month was estimated at 3130 € after the first relapse. This cost was represented in greater part by the cost of chemotherapy drugs (66%). The use of novel agents such as thalidomide, bortezomib and lenalidomide for RRMM is highly prevalent in France from the first relapse. The associated medical cost is substantial mainly due to the cost of the new agents. [ABSTRACT FROM AUTHOR]

This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone. [ABSTRACT FROM AUTHOR]

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10−7). We identified a subgroup of patients presenting at diagnosis with both low β2-microglobulin <4 mg/l and high hemoglobin (Hb) 10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high β2-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.Leukemia (2007) 21, 2020–2024; doi:10.1038/sj.leu.2404832; published online 12 July 2007 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the therapeutic attributes and pathological conditions of the insulin-like growth factor-1 (IGF-1) receptor as an inhibitor of tumor cells growth and apoptosis in patients with multiple myeloma.

Introduction Le myélome multiple (MM) peut envahir le péritoine et générer une ascite réfractaire. Il n’existe pas de recommandation concernant le traitement de cette localisation rare. Observation Nous décrivons le cas d’un patient de 84 ans présentant un MM IgA kappa découvert sur le bilan d’une tubulopathie. Le pic d’IgA sérique initial était de 45 g/L et la plasomcytose médullaire était de 22 %. La cytogénétique n’a pas pu être réalisée. De façon plus inhabituelle il présentait une ascite exsudative majeure dont l’analyse anatomopathologique montrait de nombreux plasmocytes atypiques. Un traitement par bortezomib, dexaméthasone et cyclophosphamide était débuté. Après 8 cures, l’évolution générale était favorable avec une bonne réponse partielle et un pic IgA à 11 g/dL. Il persistait néanmoins une ascite myélomateuse réfractaire importante nécessitant des ponctions itératives environ tous les 15 jours. Le traitement a donc été complété par des injections de 40 mg de dexaméthasone en intrapéritonéal tous les mois associées à un traitement systémique à dose réduite par lenalidomide et dexaméthasone. L’évolution de l’ascite était alors favorable à 4 mois avec transformation de l’exsudat en transsudat (protéines diminuant de 50 g/L à 28 g/L), disparition des plasmocytes de l’épanchement (480/mm 3 avant traitement contre 5/mm 3 lors de la dernière ponction) et diminution de la fréquence des ponctions d’ascite. Discussion Une vingtaine de cas de localisation péritonéale de MM ont été décrits [1] , la plupart compliquant des MM à IgA [2] . Le pronostic est sévère avec une survie médiane de 2 mois à l’apparition de l’ascite, avant l’avènement des traitements les plus modernes [1] Ces atteintes constituent des « localisations sanctuaires » parfois résistantes au traitement systémique. Nous rapportons le premier cas de traitement par dexaméthasone par voie intrapéritonéale qui a permis une nette amélioration clinique et paraclinique du patient. Le risque de complication infectieuse iatrogène est néanmoins élevé chez ces malades fortement immunodéprimés, et reste à préciser. Conclusion La chimiothérapie systémique semble peu active sur les localisations péritonéales de MM. Une corticothérapie intrapéritonéale pourrait être une option prometteuse. Le rapport bénéfice-risque notamment concernant le risque infectieux reste à évaluer. [ABSTRACT FROM AUTHOR]

A letter to the editor on improvement in treatment of patients with multiple myeloma, is presented.

Not available.