1 Hematology Dept., Istituto Nazionale per lo Studio e la Cura dei Tumori, University of Milan, Italy
2 Hematology Dept., University of Udine
3 Hematology Dept., University of Modena
4 Hematology ...Dept., University of Verona, Italy
5 Hematology Dept., Azienda Ospedaliera San Carlo, Potenza
6 Chair of Hematology, University of Milan, Italy
Correspondence: Lucia Farina, MD, Division of Hematology-Bone Marrow Transplantation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy. E-mail: lucia.farina{at}istitutotumori.mi.it
Background: The graft-versus-leukemia effect is able to induce clinical responses in patients with chronic lymphocytic leukemia treated with a reduced intensity conditioning regimen, followed by allogeneic stem cell transplantation. We investigated whether molecular remissions could be attained after reduced intensity conditioning and allogeneic stem cell transplantation in patients with relapsed chronic lymphocytic leukemia and whether the assessment of minimal residual disease might be used to predict the clinical outcome.
Design and Methods: Minimal residual disease was monitored by polymerase chain reaction using the immunoglobulin heavy-chain gene rearrangement as a molecular marker in 29 relapsed patients who achieved complete remission following reduced intensity conditioning and allogeneic stem cell transplantation. A nested-polymerase chain reaction with patient-specific primers derived from complementarity determining regions (CDR2 and CDR3) was carried out in all the patients. Real-time polymerase chain reaction was performed in patients whose nested reaction gave positive or mixed results.
Results: Three patterns of minimal residual disease were observed: negative (31%), mixed (24%), and always positive (45%). The cumulative incidence of relapse according to the minimal residual disease status at 6 and 12 months after transplantation was significantly different between polymerase chain reaction-negative and -positive patients ( p =0.031 and p =0.04, respectively). Two-year disease-free survival was 93% and 46% for polymerase chain reaction-negative and -positive patients at 6 months after transplantation, respectively ( p =0.012). Similarly, 2-year disease-free survival was 100% and 57% for polymerase chain reaction-negative and -positive patients at 12 months, respectively ( p =0.037). No clinical or biological factors were predictive of the achievement of polymerase chain reaction negativity after allogeneic stem cell transplantation. Graft-versus-host disease was more frequent in patients who did not relapse ( p =0.04). Quantitative monitoring of minimal residual disease was able to identify polymerase chain reaction-positive patients with a higher risk of relapse.
Conclusions: These findings demonstrate that relapsed patients can achieve molecular remission after reduced intensity conditioning and allogeneic stem cell transplantation and suggest a minimal residual disease-driven intervention that might be useful to prevent overt hematologic relapse.
Key words: chronic lymphocytic leukemia, minimal residual disease, allogeneic stem cell transplantation.
Aims. To ascertain the causes of deaths among a very large cohort of heroin injecting drug users (IDUs) who, from 1985 to 1998, attended 36 Public Health Authority Centres for Drug Users (PCDUs) in ...north‐eastern Italy.
Design. Retrospective analysis of data, obtained from the Annual Register of each Centre and the Municipal Registry Office of each local health district.
Setting. Thirty‐six PCDUs in north‐eastern Italy and Medical Service for Addictive Disorders of the University of Verona.
Participants. All IDUs who had sought medical care at least once in the PCDUs during the study period.
Findings. Of 2708 deaths, overdose was found to be the major cause (37%), followed by AIDS (32.5%) and road accidents (9.4%). The percentage of deaths due to AIDS increased steadily from 2.7% in 1985 to 42.2% in 1996, and then decreased to 16.9% in 1998. Deaths due to overdose remained almost constant. The average age of death per year rose from 26 in the mid eighties to 34 in 1998. The mortality rate among IDUs proved much higher compared to the general population of the same age (13‐fold, 95% CI, 11.3‐14.6). The proportion of all deaths attributable to regular use of illegal opiates in the 15‐34 age group in the general population in 1991 was 16%. HIV prevalence was not a significant factor in suicides and deaths by overdose.
Conclusions. The mortality rate was 13 times greater than in the general population. To be female and to have dropped out of any kind of treatment proved an important risk factor for overdose. The fall in deaths from AIDS enhances the problem to prevent and treat HCV infection. Decisions in drug projects, in research and in training should be influenced by the strikingly high percentage of deaths due to drug use.
Cluster analysis is used in several research areas to classify data sets in groups by their similar characteristics. Metaheuristic-based techniques, such as Genetic Algorithms (GAs) and Ant Colony ...Optimization (ACO), have been applied in order to increase the clustering algorithm performance. GA and ACO-based clustering algorithms are capable of efficiently and automatically forming natural groups from a pre-defined number of clusters. This paper presents a GA and an ACO algorithm to the clustering problem. Both algorithms were refined using local search in order to improve the clustering accuracy. The results are compared on numeric UCI databases.
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