Study of prognosis in acute myeloid leukemias (AML) by cluster analysis

BACKGROUND. Cluster analysis is particularly effective in detecting homogeneous subgroups among large series of observations. We applied this relatively uncommon approach to the study of prognosis in 137 patients affected by acute myeloid leukemia (AML). METHODS AND RESULTS. Employing simple presentation parameters (age, WBC, splenomegaly, hepatomegaly) we used cluster analysis to define 3 groups with different overall survival (p = 0.0019). This classification was obtained following a rescaling of the variables and principal component analysis. Validation was performed through random definition of a control group. With the same variables, univariate analysis demonstrated age was the only prognostic factor, while Cox's model was not significant. CONCLUSIONS. In our series cluster analysis allowed a better definition of prognosis than Cox's analysis. Since the 3 groups are well identifiable, each patient can be rapidly classified and his allocation confirmed by discriminant functions. For cluster 2 we were able to project a possible myelodysplastic evolution, while cluster 3 was more frequently associated with a monocytic blastic component. We think that cluster analysis deserves consideration as an alternative statistical approach in the analysis of large series of data; its usefulness lies in its power to define homogeneous prognostic or biologic subgroups and to elaborate further hypotheses for new studies

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57–2.42;P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months;P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients. © 2000 Cancer Research Campaig

Toll-Like Receptor Agonists Synergize with CD40L to Induce Either Proliferation or Plasma Cell Differentiation of Mouse B Cells

In a classical dogma, pathogens are sensed (via recognition of Pathogen Associated Molecular Patterns (PAMPs)) by innate immune cells that in turn activate adaptive immune cells. However, recent data showed that TLRs (Toll Like Receptors), the most characterized class of Pattern Recognition Receptors, are also expressed by adaptive immune B cells. B cells play an important role in protective immunity essentially by differentiating into antibody-secreting cells (ASC). This differentiation requires at least two signals: the recognition of an antigen by the B cell specific receptor (BCR) and a T cell co-stimulatory signal provided mainly by CD154/CD40L acting on CD40. In order to better understand interactions of innate and adaptive B cell stimulatory signals, we evaluated the outcome of combinations of TLRs, BCR and/or CD40 stimulation. For this purpose, mouse spleen B cells were activated with synthetic TLR agonists, recombinant mouse CD40L and agonist anti-BCR antibodies. As expected, TLR agonists induced mouse B cell proliferation and activation or differentiation into ASC. Interestingly, addition of CD40 signal to TLR agonists stimulated either B cell proliferation and activation (TLR3, TLR4, and TLR9) or differentiation into ASC (TLR1/2, TLR2/6, TLR4 and TLR7). Addition of a BCR signal to CD40L and either TLR3 or TLR9 agonists did not induce differentiation into ASC, which could be interpreted as an entrance into the memory pathway. In conclusion, our results suggest that PAMPs synergize with signals from adaptive immunity to regulate B lymphocyte fate during humoral immune response

Potenzialità energetiche delle biomasse residuali in Sardegna

In questo lavoro vengono riportati i risultati di un’analisi condotta in Sardegna per la valutazione delle potenzialità energetiche delle biomasse residuali maggiormente significative e del loro potenziale contributo al soddisfacimento del fabbisogno di energia elettrica e termica della regione, prendendo in considerazione anche i connessi aspetti ambientali. Tali risultati mostrano la disponibilità di importanti quantità di biomasse residuali, di differenti tipologie, in grado di fornire un rilevante contributo al fabbisogno energetico dell’Isola. A dispetto dei problemi che l’impiego delle biomasse a fini energetici pone, gli aspetti positivi connessi con il loro sfruttamento sono notevoli, soprattutto in termini di riduzione dell’uso di combustibili fossili e delle conseguenti emissioni

Potenzialità energetiche delle biomasse residuali in Sardegna

In questo lavoro vengono riportati i risultati di un’analisi condotta in Sardegna per la valutazione delle potenzialità energetiche delle biomasse residuali maggiormente significative e del loro potenziale contributo al soddisfacimento del fabbisogno di energia elettrica e termica della regione, prendendo in considerazione anche i connessi aspetti ambientali. Tali risultati mostrano la disponibilità di importanti quantità di biomasse residuali, di differenti tipologie, in grado di fornire un rilevante contributo al fabbisogno energetico dell’Isola. A dispetto dei problemi che l’impiego delle biomasse a fini energetici pone, gli aspetti positivi connessi con il loro sfruttamento sono notevoli, soprattutto in termini di riduzione dell’uso di combustibili fossili e delle conseguenti emissioni