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Biomedical subjects

M Brugiatelli

Publications and source records attributed to M Brugiatelli.

At least 37 records · Page 2Linked to original sources
PubMed1995

Treatment of chronic lymphocytic leukemia in early and stable phase of the disease: long-term results of a randomized trial.

In 1982 the IGCI CLL cooperative group decided to investigate the usefulness of treating, at diagnosis B-cell chronic lymphocytic leukemia (CLL) in early and stable phase of the disease. From January 1982 to December 1986, 148 patients were randomized either to receive immediate treatment with chlorambucil (CLB) or to defer therapy to the time of progression. The early and stable phase of the disease was defined by a total tumor mass (TTM) score < 9, the absence of anemia or thrombocytopenia and a doubling time > 12 months. The main end-point of the study was survival. At the last evaluation in April 1993, after a median follow-up of 75 months, no significant difference was found in overall survival between early vs. deferred treatment patients from every cause of death as well as from death due to CLL-related causes only. The same results were obtained when the patients in more favorable stages, such as Binet stage A and TTM < 4.5, were considered. Interestingly, the incidence of epithelial cancer was similar in the two groups. Early treatment was associated with a significantly better response and a lower progression rate. From this long-term experience, it can be concluded that immediate chemotherapy with CLB is not beneficial for CLL patients in early and stable phase of the disease in terms of survival.

Aged↗
PubMed1995

Modulation of purine analogs- and chlorambucil-induced cytotoxicity by alpha-interferon and interleukin-2 in chronic lymphocytic leukemia.

The decrease in cell viability observed in vitro from the effect of chlorambucil (CLB), fludarabine (FAMP) and 2-chlorodeoxy-adenosine (CDA) on peripheral lymphocytes from 49 untreated CLL patients was investigated by the MTT colorimetric assay. The effects of recombinant-interleukin (r-IL)-2 and alpha-interferon (alpha-IFN) on drug-induced cell death were evaluated. r-IL-2 significantly increased in vitro resistance to CLB, while purine analog cytotoxicity was slightly reduced by the cytokine. The potential in vivo significance of r-IL-2, acting as a survival signal on CLB-induced cell death, is supported by the correlation between the lowest IL-2 serum levels, the highest in vitro sensitivity to CLB and a major clinical response after CLB treatment in six out of eight CLL patients. Using 25 samples, alpha-IFN enabled CLL cells to increase resistance to CLB, CDA and FAMP in 14, eight and seven samples, respectively; conversely, alpha-IFN showed a synergism with both CLB and FAMP in six samples and with CDA in four. These results correlate with immunoenzymatic assay data showing that alpha-IFN either up- or down-regulates tumor necrosis factor and IL-1 levels in supernatants of some CLL samples. Apparently, alpha-IFN plays a dual role in regulating drug-induced cell death, while IL-2 seems to solely favor cell survival in CLL.

Antineoplastic Agents↗
PubMed1994

Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL.

PURPOSE: In 1987 the Italian Cooperative Group for the Study of hairy cell leukemia (HCL) started a prospective trial with the following three major aims: 1) to confirm the effectiveness of alpha-IFN as first-line treatment; 2) to assess the usefulness of splenectomy as consolidation treatment in patients achieving a satisfactory partial remission (PR) with alpha-IFN, and 3) to explore whether splenectomy in patients achieving complete remission (CR) with alpha-IFN can reduce the risk of relapse after discontinuation of the drug. PATIENTS AND METHODS: One-hundred seventy-seven patients with histologically-confirmed HCL were registered in the HCL88-A trial between December 1987 and January 1992. Inclusion criteria included no previous treatment and age less than 66 years. All patients received total doses of 3 MU of alpha-IFN daily for 12 months except for those who achieved early CR and would stop treatment after 6 or 9 months. Patients could be treated with different alpha-IFNs. At the time of the present analysis, 166 patients (93.8%) were fully evaluable. RESULTS: Treatment of HCL patients with alpha-IFN at the onset of the disease resulted in 28 CR (16.9%), 103 PR (62.0%), and 27 Minor Remissions (MR) (16.3%). Patients treated with different alpha-IFNs achieved similar results: the overall response rate (CR + PR + MR) was 92.7%, 97.2%, and 95.3% for patients treated with r-alpha-2a, r-alpha 2b, and alpha-N1, respectively. The presence of a leukemic phase and a poor performance status were associated with a statistically significant lower response rate. Patients who were randomly assigned and underwent splenectomy after achieving a PR had a better but not significant 4-year progression-free survival than cases randomized for observation (53% vs. 22%, p = 0.116). Overall, 5 patients died after study entry, with an actuarial 5-year survival rate of 96% for the entire group of 166 patients. After a mean follow-up time of 38 months, only one second malignancy has been recorded. CONCLUSIONS: Initial therapy with alpha-IFN, regardless of the type of alpha-IFN used, induces satisfactory responses in the majority of patients with HCL, but in most instances discontinuation of treatment results in recurrence of disease. In most cases alpha-IFN improves the performance status of patients and favors a satisfactory bone marrow recovery and thus could still play a role in the initial management of the disease. Although splenectomy following alpha-IFN could prolong the progression free survival, its use should be restricted to selected cases.

Adult↗
PubMed1994

Comparison of younger versus older B-cell chronic lymphocytic leukemia patients for clinical presentation and prognosis. A retrospective study of 53 cases.

Fifty-three patients affected with B-cell chronic lymphocytic leukemia (CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico-hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B-CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population. Sex distribution, mean peripheral lymphocyte count, platelet count, distribution among Rai's and Binet's stages, total tumor mass (TTM) score, histological pattern of bone marrow infiltration and lymphocyte doubling time (LDT) were similar to a series of 201 CLL cases older than 50 years. Only hemoglobin mean level was significantly higher in younger patients (13.1 +/- 2.1 vs 12.2 +/- 2.6 g/dl; p < 0.01). The overall median survival was 7.1 years. Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of "smoldering" CLL, had a very long survival (75% survival probability at 16 years). Life-expectancy of younger patients was significantly longer than that of older ones (median survival, 7.1 versus 4.1 years; p < 0.05). However, when the background mortality due to non-CLL related deaths (i.e., cardiovascular complications, epithelial cancers) was removed, survival advantage of young cases disappeared. In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well-defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive therapy should be made.

Adult↗
PubMed1993

Alpha 2-interferon in B-cell chronic lymphocytic leukemia: clinical response, serum cytokine levels, and immunophenotype modulation.

Fifteen patients with B-cell chronic lymphocytic leukemia (B-CLL) have been treated with alpha 2b-interferon (alpha IFN) for one year (3 mega units subcutaneously three times a week). The hematological response and the modulation of immunophenotype, serum levels of soluble interleukin-2 receptor (sIL-2R) and tumour necrosis factor (TNF) have been monitored. Hematologically 67% of cases were classified as responders, although no complete responses were observed; three cases progressed during treatment, and two patients showed stable disease. Both peripheral lymphocytes and CD24+ cell absolute number significantly decreased after twelve months of IFN treatment (40.7 +/- 17 x 10(9)/l versus 15.8 +/- 6 x 10(9)/l, mean values +/- sd, p < 0.01, and 30.4 +/- 5.5 x 10(9)/l versus 8.1 +/- 2.8 x 10(9)/l, p < 0.05, respectively), while CD24+ cell percentage did not change (72.1% +/- 4.6 versus 67.5% +/- 8.8, p not significant). In the majority of cases myelomonocytic markers (CD11c, CD14, CD11b) transitorily decreased during the treatment. Serum sIL-2R levels, elevated in all cases before IFN treatment, increased in responders. Serum TNF levels decreased in patients showing high values before the treatment. The explanation of these findings and their possible implication are discussed.

Aged↗
PubMed1992

A short multilingual quality of life questionnaire--practicability, reliability and interlingual homogeneity.

International cooperative clinical trials require a multilingual quality of life questionnaire. The 'International Society for Chemo- and Immunotherapy' therefore designed a study to develop and test a 'health accentuated' quality of life questionnaire in the eight languages spoken in this society. The objective was to examine practicability, reliability and interlingual homogeneity. Versions of the questionnaire in Czech, German, Hungarian, Italian, Kroatian, Polish, Romanian and Slovakian have been prepared. The results are based on data of 1,104 adult patients. They demonstrate that the developed questionnaire is practicable. Patients need 10-15 min to answer it, usually without assistance. The proportion of missing values is for all but two questions less than 3%. The questionnaire also found high acceptance reflected by only 2.7% refusals. It is reasonably reliable in each language. Interlingual homogeneity could be shown by demonstration of strong structural similarities between the different versions using multidimensional scaling, factor analysis and comparison of mean profiles.

Adolescent↗
PubMed1992

Alpha thalassaemia hydrops fetalis in the UK: the importance of screening pregnant women of Chinese, other South East Asian and Mediterranean extraction for alpha thalassaemia trait.

OBJECTIVE: Alpha zero (alpha 0 or alpha-1) thalassaemia is an important genetic risk for women originating from Hong Kong, Singapore, Vietnam, Thailand, the Philippines or South China. Cypriots are also at risk. Carriers of alpha zero thalassaemia trait can be detected by routine haemoglobinopathy screening. When a couple are both carriers, in each pregnancy there is a 25% risk that the fetus will have alpha thalassaemia hydrops fetalis; this is fatal for the fetus and carries serious obstetric and psychological risks for the mother. Most informed couples at risk request prenatal diagnosis and selective abortion. This study investigates the effectiveness of screening, counselling and prenatal diagnosis for alpha thalassaemia hydrops fetalis in the UK. DESIGN: Retrospective analysis of the notes. SUBJECTS: 18 couples attending University College Hospital London for prenatal diagnosis of alpha thalassaemia hydrops fetalis since 1982. RESULTS: The study shows underdiagnosis of both alpha zero thalassaemia trait and alpha thalassaemia hydrops fetalis leading to avoidable stillbirths and complications in pregnancy. CONCLUSION: We recommend early screening for alpha zero thalassaemia trait for all women of Southeast Asian or eastern Mediterranean origin and the offer of prenatal diagnosis when indicated. The diagnosis of alpha thalassaemia hydrops fetalis should be considered in women of the relevant ethnic origin who have a stillbirth, neonatal death, abnormal ultrasound findings at fetal anomaly scanning (especially a large placenta), or who develop pre-eclampsia.

Abortion, Spontaneous↗
PubMed1992

Factors affecting the uptake of prenatal diagnosis for sickle cell disease.

Between 1979 and 1990, 170 couples at risk of having children with sickle cell disease, resident in the UK and with a continuing pregnancy, were referred for counselling at the University College Hospital Perinatal Centre. Approximately 50% of the couples, including those where one partner actually had sickle cell disease, requested prenatal diagnosis. This was requested in 82% of pregnancies when the mother was seen in the first trimester of pregnancy and in 49% when she was seen in the second trimester. More than 90% of referred couples who already had an affected child requested prenatal diagnosis. The type of sickle cell disease involved and ethnic group also influenced choice. These results show the importance of detecting and counselling couples at risk before pregnancy whenever possible.

Anemia, Sickle Cell↗
PubMed1992

Childhood acute lymphoblastic leukemia immunophenotypes and their prognostic significance: experience of the IGCI-study in 389 children. International Society for Chemo-immunotherapy (IGCI-Vienna) Cooperative Group.

The prognostic significance of immunophenotype and other features including sex, age, anaemia, WBC, FAB type, and PAS staining were analysed in a group of 389 children newly diagnosed as acute lymphoblastic leukemia (ALL) and treated according to the BFM 1981/1983 protocol. The CR rate was higher (82-94%) in immunophenotypic subgroups defined as 'non-B' compared with B-ALL (54%). The probability of being in CCR at the end of follow up was 0.68 (median. observation, 3 years). Using the stepwise Cox regression analysis the following independent factors predictive of duration of CCR were selected (relative risk in brackets): 1. WBC (> 25G/1:< 25G/1 = 2.0, P = 0.0008), 2. age (> 10y:2-10y = 1.3, P = 0.04), 3. CALLA positivity (neg.:posit. = 2.4, P = 0.04), 4. CALLA within B-cell progenitor ALL (pre;preB,Calla-:Calla+ = 1.7, P = 0.007). T-ALL appeared to have a worse prognosis than U-ALL and B-progenitor derived ALL but it did not retain independent prognostic significance in multivariate analysis.

Adolescent↗
PubMed1989

Immunologic and molecular evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical remission phase.

This study evaluates residual disease in 28 B-cell chronic lymphocytic leukemia (B-CLL) patients who obtained a clinicohematologic remission after intensive chemotherapy. Sixteen of 28 patients (57%) showed a normal number of circulating B-lymphocytes, as demonstrated by the low percentage of mouse rosette-forming cells (M-RFC), surface immunoglobulins (SIg), and CD24-positive cells. Clinically, a lower number of relapses occurred in this group of patients compared to those with a persistent expansion of peripheral B-cells (P less than 0.05). In order to assess monoclonality of the residual peripheral B-cell population, the distribution of SIg light chains was investigated on the B-cell-enriched fraction of 15 of these 16 cases. Only six of them had a kappa/lambda ratio which ranged between 1.7:1 and 3:1, whereas the remaining patients still displayed a clearly imbalanced kappa/lambda Ig light chain distribution. On the other hand, the analysis of the configuration of the Ig heavy chain gene region, performed in nine cases (including five of the above six cases), showed the persistence of a rearranged pattern in all cases tested but one. Therefore, residual monoclonal B-cells were found also in the majority of cases which displayed the lowest kappa/lambda ratio, a normal bone marrow lymphocytosis and a long-lasting clinical remission. Studies at the DNA level confirm that a remission is rarely achieved in this disease in spite of intensive and prolonged chemotherapy. Nonetheless, the follow-up of B-CLL patients by conventional immunologic markers may be helpful to better define response to therapy and to predict the occurrence of clinical relapse.

B-Lymphocytes↗
PubMed1989

The expression of CD 15 antigen on myeloid leukaemia cells--a new prognostic index for complete remission and for survival.

377 untreated acute leukaemia patients were categorized according to FAB and cytochemical criterials and simultaneously phenotyped with the use of 6-21 monoclonal antibodies (MoAb) of VI series (W. Knapp, Vienna). The leukaemia phenotype was compared with the patients outcome after treatment. In adult ANLL patients a positive relationships was proved statistically between the expression of the CD 15 cell differentiation antigen on leukaemic blasts and the CR rate (p less than 0.01, chi 2 test). Also a comparison of the Kaplan-Meier survival curves revealed that the CD 15 positive group of ANLL patients has a better outcome than the CD 15 negative one (p less than 0.01, by Wilcoxon and Log-rank tests). Thus, examination of cell differentiation antigens could be a useful addition to existing risk assignment in acute leukaemia.

Antibodies, Monoclonal↗
PubMed1988

High dose continuous chlorambucil vs intermittent chlorambucil plus prednisone for treatment of B-CLL--IGCI CLL-01 trial.

279 B-CLL patients entered randomized IGCI clinical trial to compare the remission rate and survival of high dose continuous chlorambucil (regimen A) vs intermittent chlorambucil plus prednisone (regimen B), and to assess the effect of early treatment on survival. Regimen A was significantly better for remission induction (p less than 0.001), and prolonged survival (p less than 0.01) in comparison to regimen B. More aggressive chemotherapy is associated with better response but requires close monitoring of both antineoplastic effect and haematological toxicity. Total tumor mass score (TTM) proved to be suitable for definition of both early, stable disease and the response to therapy because of its quantitative continuous character and its independence of bone marrow failure. This system is helpful for the detection of treatment toxicity and consequently enables safe monitoring of therapy. Although statistically significant difference has not yet been reached between the patients treated early and non treated patients the latter group seems to fare better.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Non-Hodgkin's lymphoma associated with sickle cell disease: a case report.

A case of non-Hodgkin's lymphoma with leukemic spread in a patient affected with homozygous sickle cell disease is reported. This association has not been previously described. A correlation between the malignancy and the hemoglobinopathy could not be etiologically ascertained; therefore, an alternative explanation to a chance event cannot be offered.

Anemia, Sickle Cell↗