Search PubMed⌕ Search

Biomedical subjects

F Lauria

Publications and source records attributed to F Lauria.

At least 73 records · Page 4Linked to original sources
PubMed1993

Fludarabine: an active agent in the treatment of previously-treated and untreated low-grade non-Hodgkin's lymphoma.

BACKGROUND: Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with a promising therapeutic activity in the lymphoproliferative disorders. PATIENTS AND METHODS: We performed a phase II study with this drug in previously untreated and treated patients with resistant and/or relapsed low-grade non-Hodgkin's lymphoma (LG-NHL) to determine its response rate. Twenty-one patients were treated at a dosage of 25 mg/m2 per day for 5 consecutive days. RESULTS: Of the 21 patients, 3 achieved complete responses (CR) and 11 partial responses (PR). In addition, three patients obtained minor responses, and the remaining 4 showed no benefit from the treatment. An increased response rate was achieved in 8 untreated patients in which 3 CR and 3 PR were documented. Furthermore, 4 of the 5 patients showing a leukemic blood picture experienced significant reductions of lymphocyte count and 2 patients with macroglobulinemic lymphomas experienced significant reductions of the IgM monoclonal component from 7.8 and 5.9 g/100 mL to 1.0 and 1.1 g/100 mL, respectively. The toxicity on platelets was negligible. The major toxic effects observed were neutropenia (62%) and infections and/or febrile episodes (19%) that were fatal to only one patient. CONCLUSIONS: In consideration of its significant activity, the role of FLU needs to be further evaluated in the management of pretreated and untreated patients with LG-NHL.

Adult↗
PubMed1993

Fludarabine in patients with advanced and/or resistant B-chronic lymphocytic leukemia.

In this study, we evaluated the efficacy of fludarabine (FLU), an adenine nucleoside analogue, in 35 previously treated patients with advanced and progressed B-cell chronic lymphocytic leukemia (B-CLL) and in 6 at diagnosis. All patients were treated at a dose of 25 mg/m2 per day for 5 consecutive days (mean number of courses was 5, with a range from 4 to 6). The majority of patients experienced a beneficial effect on hematological parameters. In particular, a remarkable reduction of lymphocyte count together with an increase of neutrophils and platelets was observed. The overall response rate was 42% with 1 complete response and 16 partial responses. Ten patients achieved minor responses and the remaining 14 showed no benefit from treatment. An increased response rate was achieved in 6 untreated patients who showed an overall response rate of 67% (4/6). The major complications observed were neutropenia (66%) and febrile episodes (44%) that were generally infection-related and were fatal in 3 cases. Because we were dealing with patients whose disease was advanced and/or resistant to treatment, the overall results may be considered encouraging with acceptable toxic reactions not superior to those frequently observed with polychemotherapy.

Adult↗
PubMed1993

High complete remission rate in hairy cell leukemia treated with 2-chlorodeoxyadenosine.

2-Chlorodeoxyadenosine (2-CdA), a purine nucleoside, has been shown to be remarkably effective in the treatment of patients with hairy cell leukemia (HCL). We hereby report on the results achieved in 26 HCL patients treated with one single course of 2-CdA at a dose of 0.1 mg/kg daily for 7 days continuous infusion. Twenty-four were males and 2 females, with a median age of 56 years; all but 5 had been previously treated with Interferon-alpha (IFN-alpha). All cases are fully evaluable for their clinical and hematological response. Twenty of them (77%) achieved a complete remission and 6 a partial remission; two of the latter progressed after 6 and 12 months, respectively. The median duration of response was 13.8 months, ranging from 7 to 22 months from the end of therapy. Circulating hairy cells and spleen enlargement, when present, disappeared within 2 weeks after completing treatment; furthermore, a rapid normalization of soluble Interleukin-2 receptor serum levels was observed in all complete responders but one, and in 2 of the 6 partial responders. A significant lymphocytopenia was observed in almost all patients, whilst a severe neutropenia (< 500/microliters) was registered mainly in the 10 patients who had less than 1,000/microliters neutrophils when treatment was started; the hemoglobin and platelets were marginally affected in only a few cases. Eight of the 10 patients who developed severe neutropenia experienced fever; in 4 of them it was short-lived (24 hours) and apparently not infection-related, while the remaining 4 probably had an infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A comparative analysis of the sensitivity of multidrug resistant (MDR) and non-MDR cells to different anthracycline derivatives.

Because of the fact that tumor cell sensitivity to cytotoxic agents may play a major role in cancer treatment, and several anthracyclines are widely used for first-line treatment of leukemia, lymphoma and other tumors, and since the overexpression of the mdr-1 gene-coded 170 Kd glycoprotein (P170) decreases cell sensitivity to anthracyclines, we investigated the relationship between P170 overexpression and the cytotoxicity of two classic anthracyclines (Daunorubicin or DNR and Doxorubicin or DX) and two lipophilic anthracycline derivatives (Idarubicin or IDA and Iododoxorubicin or IDX). For these purposes, we used multidrug resistant (MDR) and non-MDR tumor and leukemia cell lines and the MTT-microcultured tetrazolium colorimetric assay. We showed that mdr-1 gene overexpression was strongly associated with the development of a high level of resistance to DNR and DX, but not to the derivatives IDA and IDX. These data suggest that more lipophilic anthracycline derivatives may also be active in MDR cell systems.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Heterogeneous immunophenotype of granular lymphocyte expansions: differential expression of the CD8 alpha and CD8 beta chains.

In this study, we have evaluated 14 large granular lymphocyte (LGL) expansions, 11 of which were CD8+. Analysis of the membrane expression of the alpha and beta chains of the CD8 antigen, using specific monoclonal antibodies (MoAbs), has shown that LGL expansions with the CD3+, CD4+, CD8+, CD57+ T-cell receptor (TcR) alpha beta phenotype bear the CD8 alpha/alpha isoform, while the CD3+, CD4-, CD8+, CD57+ TcR alpha beta samples were positive for both the CD8 alpha and CD8 beta chains. These data were confirmed also by messenger RNA analysis. One additional case, with a peculiar phenotype (CD3-, CD2-, CD4-, CD8+, CD57-) and a germline configuration of the TcR beta and gamma chain genes, expressed only the CD8 alpha chain. After additional phenotypic analysis with a wider panel of MoAbs, it was found that the beta chain of the interleukin-2 receptor was constitutively expressed on the majority of the samples tested, and that most of the monoclonal samples coexpressed CD45RA/R0 antigens. Using MoAbs directed against the variable regions of the TcR beta chain, we could show a preferential V beta region restriction in the CD8+ monoclonal cases. This more extensive characterization of CD8+ LGL expansions has further documented the marked heterogeneity within this rare condition and allowed a better phenotypic dissection between the monoclonal and polyclonal cases.

Adult↗
PubMed1992

Results in hairy-cell leukemia patients treated with alpha-interferon: predictive prognostic factors.

Fourty-four evaluable patients with hairy cell leukemia (HCL) were treated with human lymphoblastoid alpha-interferon (alpha-IFN), at a dose of 3 x 10(6) Units a day for 12-18 months while 18 of them continued to receive a three times per week schedule at the same dose as maintenance treatment. Eighteen percent of patients achieved complete response, 64% partial response, and 18% minor response with a median duration of 37.5, 22.9 and 3.5 months respectively. Twenty patients (45%), all partial or minor responders, subsequently had progression of the disease. The progression occurred more frequently in patients who presented at diagnosis with a hairy-cell index value > 0.50 than in those who presented with a hairy-cell index < 0.50: 14/26 (54%) versus 2/11 (18%) respectively. In addition, the progression rate was more evident in "non-maintained" than in "maintained" patients: 16/26 (61.5%) versus 4/18 (22%). Restarting alpha-IFN treatment in 16 of the 20 progressed patients proved effective only in 9 of them. From these findings it appears that a low hairy-cell index at diagnosis correlates favorably with a good hematological response. Furthermore, continuous therapy with alpha-IFN seems very useful in reducing the progression of the disease, in particular in patients with a very high hairy-cell index at diagnosis.

Adult↗
PubMed1992

Serum soluble interleukin-2 receptor levels in hairy cell leukemia: correlation with clinical and hematological parameters and with alpha-interferon treatment.

The soluble Interleukin-2 Receptor (sIL-2R) serum levels were assessed in 42 patients with Hairy-Cell Leukemia (HCL) at diagnosis and after alpha-Interferon therapy and correlated with spleen size, peripheral hematological values, hairy cell index (HCI) and clinical response. Serum sIL-2R levels were significantly increased in all HCL patients, particularly in those with a higher HCI (> 0.50) and in non-splenectomized patients. Among the 26 HCL patients who were studied before and after 12 months of alpha-IFN treatment, 16 normalized the sIL-2R level and 10 did not. Our findings suggest that sIL-2R levels in HCL patients correlate with the splenic and bone marrow tumor burden as assessed by HCI. In addition patients with low levels of sIL-2R at diagnosis appear to have a better chance of achieving a good clinical response.

Biomarkers, Tumor↗
PubMed1992

Biological markers and minimal residual disease in hairy cell leukemia.

Soluble Interleukin-2 Receptor (sIl-2R) and Tumor Necrosis Factor-alpha (TNF-alpha) have been found significantly increased in serum samples of patients with HCL at diagnosis and a strict correlation with leukemic burden has been reported. Furthermore, following therapy, serological monitoring of these cytokines may be considered a useful tool for controlling therapeutic efficacy and for detection of minimal residual disease. Eighteen HCL patients, treated with 2-Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days, entered the study all of them showing increased levels of sIL-2R and TNF-alpha prior to therapy. After therapy, serum levels were reassessed and a remarkable decrease was recorded in all cases. In particular, after 1 month by the end of treatment sIL-2R and TNF-alpha decreased from 3,377 +/- 2,303 to 149 +/- 96 pM/ml (p = 0.00003) and from 38 +/- 41 to 18 +/- 18 pg/ml (p = 0.015) respectively. The only 3 patients who did not normalize sIL-2R and TNF-alpha levels showed also an evident persistence of the disease in the marrow. In conclusion, 2-CdA leads to a rapid normalization of the increased levels of sIL-2R and TNF-alpha in the majority of HCL patients. Furthermore, monitoring of these cytokines represents a useful tool for detecting minimal residual disease.

Adult↗
PubMed1991

Defective lymphokine-activated killer cell generation and activity in acute leukemia patients with active disease.

In 26 myeloid and lymphoid acute leukemia patients at presentation the capacity to generate interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells effective against the natural killer (NK)-resistant Raji cell line, as well as the susceptibility of the blasts to normal peripheral blood (PB) LAK cells and to autologous LAK effectors was analyzed. The overall PB LAK activity against Raji cells was significantly lower in acute leukemia patients compared with normal controls (mean, 1,473 +/- 971 SD LU/10(8) LAK effectors v 3,340 +/- 1,862; P less than .001). The sensitivity of the blasts to autologous LAK cells was also significantly lower than to normal LAK effectors (517 +/- 593 LU/10(8) LAK effectors v 1,304 +/- 1,066; P less than .01). When the data were analyzed independently, four patterns of behavior could be recognized. The relatively largest group (9 of 26) included patients in whom effective LAK cells could be generated against the Raji line, but in whom the blasts were resistant to autologous PB-LAK effectors while being susceptible to normal LAK cells (defective specific LAK activity). In 5 of 26 cases, an incapacity to generate LAK activity against both allogeneic and autologous target cells was observed (defective LAK generation). In six further cases, the blasts were resistant to both allogeneic and autologous LAK populations, though the latter were effective against the Raji line (resistant blasts). The same defects could also be shown with bone marrow-derived LAK cells. Only in six cases did the leukemic blasts appear susceptible to autologous and allogeneic LAK cells. In four patients the analysis could be repeated at remission, and in three a restoration of the LAK function against the primary blasts was recorded. In the 10 cases studied at relapse, the blasts were resistant to autologous LAK effectors in nine and to normal LAK in seven. These data demonstrate that in most acute leukemia patients with active disease, a defect of the LAK machinery, either a deficient generation of LAK cells or the resistance of the blasts to LAK effectors, may be documented, pointing therefore to a possible contributory role of the LAK system in the control of leukemic cell growth. In view of the frequent normalization of the autologous LAK activity at the time of remission, immunotherapy with IL-2/LAK cells should be primarily aimed to patients with minimal residual disease.

Cell Line↗
PubMed1991

Comparison of low-dose versus standard-dose alpha-interferon regimen in the hairy cell leukemia treatment.

In a randomized clinical trial, the effects of standard doses of alpha-interferon (alpha-IFN) compared with the effects of half of these doses were evaluated in patients with hairy cell leukemia. There were 14 patients treated with standard-dose (3 MU/day i.m. for 6 months, then 3 MU three times/week for a further 6 months) and 10 patients with low-dose alpha-IFN (1.5 MU/day with the same schedule and for the same period). The overall response rate, the quality, and the duration of response were rather similar in both groups. The rapidity of response in normalizing the peripheral blood counts was similar, even increased in low-dose-treated patients, consisting mainly in clearing the number of circulating hairy cells (p less than 0.03). Finally, the toxic effects of both regimens were minimal but less evident in patients treated with low-dose alpha-IFN. Despite the small number of patients, on the basis of this report, we can confirm that 1.5 MU/day of alpha-IFN is an adequate treatment for patients with hairy cell leukemia.

Adult↗
PubMed1990

Reduced hematologic response to alpha-interferon therapy in patients with hairy cell leukemia showing a peculiar immunologic phenotype.

Alpha-interferon (alpha-IFN) treatment is highly effective in normalizing the clinical, hematologic, and immunologic parameters of patients with hairy cell leukemia (HCL). Complete remissions (CR), however, are rare, and a few patients do not respond adequately to alpha-IFN. That the poor response to alpha-IFN treatment could be related to a particular immunologic surface marker profile of the HC was investigated in this study. The results showed that most patients who do not respond adequately to alpha-IFN HC have a peculiar immunologic phenotype with a positive response to the Leu1 (CD5) monoclonal antibody, usually absent on HC but characteristically expressed on B-chronic lymphocytic leukemia cells. Of nine HCL patients with this phenotype, only three had partial remissions (PR) and six minor responses (MR) compared with the three CR, 16 PR, and three MR observed in the 22 Leu1 (CD5)-negative patients. The authors postulate that a more extensive immunologic analysis of HCL patients at diagnosis may be predictive of the response to IFN treatment.

Adult↗
PubMed1990

Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo.

To evaluate the occurrence of hypercoagulability during treatment with L-asparaginase (L-ase), thrombin-antithrombin complex (TAT) and D-dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. L-ase alone (20,000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to L-ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second L-ase infusion. Increased levels of TAT (P less than 0.05) and D-dimer (P less than 0.01) were observed prior to L-ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with L-ase alone, further elevation of TAT (P less than 0.05) and persistence of increased D-dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of D-dimer levels occurred during L-ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by L-ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to L-ase treatment remains to be determined.

Antithrombin III↗
PubMed1990

Selection of a panel of monoclonal antibodies for monitoring residual disease in peripheral blood and bone marrow of interferon-treated hairy cell leukaemia patients.

A panel of monoclonal antibodies (mAbs) directed against B-cell and hairy cell leukaemia (HCL)-associated antigens was used to identify residual hairy cells in the peripheral blood and/or bone marrow samples from 20 patients with HCL, following treatment with interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta). In all cases, hairy cells retained their characteristic phenotype, e.g. positivity for CD22, CD11c, CD25, CD32, and the HCL-associated trimeric protein (t-GP) recognized by the mAbs HML-1, B-ly7, LF61 and Ber-Act8. The most specific marker for identifying a small percentage of hairy cells in peripheral blood cytospins, was t-GP. In alkaline phosphatase/anti alkaline phosphatase (APAAP) stained preparations, t-GP+ hairy cells (provided with large cytoplasm and hairy surface) could be usually distinguished from t-GP+ normal lymphocytes (small-sized cells with smooth surface). In doubtful cases the percentage of residual hairy cells could exactly be estimated by double immunofluorescence staining for CD22 (B-cell marker) and t-GP. The rationale of the test is based on the finding that the small percentage (about 1%) of t-GP+ lymphocytes circulating in the peripheral blood of normal individuals are T-cells of the CD8 subset and not B-cells. The best markers for identifying residual hairy cells in routine bone marrow biopsies were CD45RA (mAb 4KB5) and CD20 (mAb L26). Immunohistological labelling was superior to morphological examination in picking up scattered hairy cells in bone marrow biopsies showing either severe hypoplasia or exuberant hyperplasia of normal haemopoietic series.

Antibodies, Monoclonal↗
PubMed1990

Relationship between immunological phenotype and hematological response to alpha-IFN treatment in 35 patients with hairy cell leukemia.

During the past 6 years, clinical trials employing alpha-interferon (alpha-IFN) in hairy cell leukemia (HCL) have shown dramatic improvement in the management of this disease. Complete remissions (CR), however, are relatively rare (10-15%) and a minority of patients (10-25%) do not respond adequately to alpha-IFN. The possibility that the poor response to alpha-IFN treatment could be related to a peculiar immunological phenotype of the hairy cell (HC) was investigated in this study. The results demonstrated that, in the majority of patients who failed to respond to alpha-IFN, HC showed an immunological phenotype characterized by positivity with the CD5 monoclonal antibody which is usually absent on HC and characteristically expressed on B-chronic lymphocytic leukemia cells. In fact, among the 10 HCL patients who presented with this phenotype, only 5 partial remissions (PR) and 5 minor responses (MR) were achieved, as opposed to the 3 complete remissions (CR), 19 PR and 3 MR observed in the 25 CD5-negative patients. The possibility that a more extensive immunological analysis of HCL patients at diagnosis may be predictive of the response to IFN treatment is postulated.

Adult↗
PubMed1990

Splenectomy after initial therapy with alpha-IFN in patients with hairy-cell leukemia (HCL): a multi-center study by the Italian Cooperative Group for HCL. Preliminary results.

Since December 1987, 115 patients with HCL have been enrolled in a prospective multicenter study to evaluate the role of splenectomy after an induction therapy with alpha interferon. The group of patients was divided into two categories: those younger and those older than 65 years. The schedule of treatment with IFN was, respectively, 1.8 MU/sm/daily and 1.0 MU/daily, 33 patients were treated with r-alpha-2a, 34 with r-alpha-2b, and 25 with alpha-Ly. To date, 92 patients are fully evaluable. The response was assessed every 3 months by bone marrow trephine biopsy. Patients in CR continued IFN therapy for 3 months and, if they were still in CR, could undergo an optional splenectomy. Patients in PR continued therapy for 12 months and subsequently were randomized for splenectomy or observation only. In these preliminary results of an ongoing protocol, CR was obtained in 5 cases (6%), PR in 59 (64%), MR in 25 (27%), NR in 3 (3%). Only 2 of the 5 patients in CR underwent splenectomy and are still in CR. Of the 59 patients in PR, only 15 completed 12 months of therapy. 9 patients in Group A were randomized, 4 were splenectomized and 5 were in the observation arm. All patients were splenectomized safely and no complications occurred. These preliminary results suggest that splenectomy could be effective in consolidating the response obtained with IFN.

Adult↗