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M Vespignani

Publications and source records attributed to M Vespignani.

At least 19 recordsLinked to original sources
PubMed2001

Risk-oriented postremission strategies in adult acute lymphoblastic leukemia: prospective confirmation of anthracycline activity in standard-risk class and role of hematopoietic stem cell transplants in high-risk groups.

INTRODUCTION: Although definite risk classes are well known, risk-adapted modulation of first-line therapy is seldom attempted in adult ALL. So, a prospective validation of the therapeutic efficacy of a protocol (or a component thereof) in specific risk groups is uncommon. MATERIALS AND METHODS: From 1996-1999 a risk-oriented program (08/96) was evaluated in 102/121 unselected patients (median age 35 years, blast count 0-450 x 10(9)/l, 100 B(lin) (lineage), 21 T(lin)) responsive to induction therapy. The standard risk (SR) class was B(lin) CD10+ Ph- with blasts < 10 x 10(9)/l (prior studies: disease-free survival (DFS) rate 52% at five years with dose-intensive anthracycline-containing programs). The SR protocol was therefore anthracycline-rich (early consolidation cycles with total idarubicin 96 mg/m2), and comprised long-term maintenance. High-risk (HR) patients were eligible to the following three options: allogeneic hematopoietic stem cell transplantation (HSCT) from related family donor; short sequence with high-dose cyclophosphamide-cytarabine-methotrexate followed by melphalan/total body irradiation with autologous HSCT; or T(lin) ALL chemotherapy regimen inclusive of high-dose cytarabine and methotrexate. RESULTS: Treatment realization and three-year DFS rates according to risk class, HR subset and postremission treatment intensity were the following. SR group (n = 28): realization rate 93%, DFS 68.5%. HR group (n = 74): realization rate 80%, DFS 39% (P = 0.052 vs SR category). In HR group, three-year DFS rates by disease subtype were the following. B(lin) Ph- (n = 35) 43%; Ph+ (n = 19) 13% at 2.7 years (P = 0.006 vs other HR subtypes); T(lin) (n = 18) 59.5%. And DFS rates by treatment intensity were: allograft (n = 21) 40%; autograft (n = 28) 27%; shift to SR protocol (n = 13) 52% (P = ns vs allograft/autograft); T(lin) program (n = 10) 57%. Matched analyses of treatment protocols and disease subtypes suggested a possible therapeutic role of the autograft regimen in B(lin) Ph- ALL with a blast count < 25 x 10(9)/l, and of T(lin) protocol for T(lin) ALL. Comparisons with retrospective control cohorts were confirmatory of anthracycline activity in SR subclass. CONCLUSION: The intended strategy was applicable to the majority of study patients, confirming the value of anthracyclines in SR class and, preliminarily, the usefulness a T(lin)-specific treatment. Apart from the case of Ph+ ALL, the indications for high-dose procedures with HSCT remains largely undetermined in this study.

Adolescent↗
PubMed1999

Fractionated cyclophosphamide added to the IVAP regimen (idarubicin-vincristine-L-asparaginase-prednisone) could lower the risk of primary refractory disease in T-lineage but not B-lineage acute lymphoblastic leukemia: first results from a phase II clinical study.

BACKGROUND AND OBJECTIVE: In a prior study, primary resistant acute lymphoblastic leukemia (RES-ALL) was observed in 11 of 176 (6%) adult patients treated with a four drug regimen (IVAP), its incidence being higher in T-cell or Philadelphia (Ph) chromosome/BCR-ABL rearrangement positive ALL cases with a blast cell count >25x10(9)/L (RES-ALL rate 19%, p=0.04). Aiming to minimize this percentage of resistant disease, fractionated cyclophosphamide (f-CY) was then added to the IVAP regimen. DESIGN AND METHODS: Study 08-96 was a prospective, collaborative phase II trial carried out at eight general hospital centers specialized in the care of hematologic malignancies. Historical IVAP-treated patients served as a retrospective control group. All consecutive, untreated patients (>15 years) with a diagnosis of ALL or advanced-stage lymphoblastic lymphoma (LBL) were eligible. RES-ALL was defined as the persistence of >5% ALL cells in the bone marrow 28-40 days after the start of the IVAP regimen (idarubicin 10 mg/m(2)/d on days 1 and 2; vincristine 2 mg on days 1, 8 and 15; L-asparaginase 6,000 U/m(2) on alternate days 3 6 from day 8; prednisone 60 mg/m(2)/d on days 1-21). In the new study, two f-CY schedules were sequentially adopted: CY 150 or 75 mg/m(2)/bd, given for 4 consecutive days before IVAP (f-CY 1200 or 600, expressing total CY dose in mg/m(2)). RESULTS: Eighty-eight patients were evaluable (age range 15-74 years, blast count 0-240x10(9)/L, 14 T-lineage, 74 B-lineage, 13 Ph/BCR-ABL+). The first 39 patients received the f-CY 1200 schedule, 22 patients received f-CY 600, and the last 27 patients were not given any f-CY. These changes were dictated by the results of interim analyses of the f-CY groups (RES-ALL rate not reduced, myelotoxicity increased). Altogether, compared with the historical IVAP and no f-CY groups, the incidence of RES-ALL was not decreased by the addition of f-CY 1200/600 in B-lineage ALL, regardless of Ph/BCR-ABL expression and blast count. However, none of 14 T-ALL cases in the new study had RES-ALL (8 in f-CY groups, 5 of whom with >25x10(9)/L blast cells), compared to 5/39 (13%, overall) or 4/21 (19%, with >25x10(9)/L blast cells) among the control cases. Owing to small sample size, this difference was not statistically significant. INTERPRETATION AND CONCLUSIONS: This preliminary experience suggests that T-ALL may be more sensitive than B-lineage ALL to an early therapy including f-CY. The hypothesis could be tested in a larger clinical trial.

Adolescent↗
PubMed1998

VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.

PURPOSE: The aim of this multicenter randomized study was to compare conventional therapy with conventional plus high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) as front-line treatment for poor-prognosis non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between October 1991 and June 1995, 124 patients, aged 15 to 60 years, with diffuse intermediate- to high-grade NHL (Working Formulation criteria), stages II bulky (> or = 10 cm), III, or IV were enrolled. Sixty-one patients were randomized to receive etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) for 12 weeks and cisplatin, cytarabine, and dexamethasone (DHAP) as a salvage regimen (arm A), and 63 to receive VACOP-B for 12 weeks plus HDT and ABMT (Arm B). RESULTS: There was no significant difference in terms of complete remissions (CRS) in the two groups: 75% in arm A, and 73% in arm B. The median follow-up observation time was 42 months. The 6-year survival probability was 65% in both arms. There was no difference in disease-free survival (DFS) or progression-free survival (PFS) between the two groups. DFS was 60% and 80% (P = .1) and PFS was 48% and 60% (P = .4) for arms A and B, respectively. Procedure feasibility was the major problem. In arm B, 29% of enrolled patients did not undergo HDT and ABMT. A statistical improvement in terms of DFS (P = .008) and a favorable trend in terms of PFS (P = .08) for intermediate-/high- plus high-risk group patients assigned to HDT and ABMT was observed. CONCLUSION: In this study, conventional chemotherapy followed by HDT and ABMT as front-line therapy seems no more successful than conventional treatment in terms of overall results. However, our results suggest that controlled studies of HDT plus ABMT should be proposed for higher risk patients.

Adolescent↗
PubMed1994

MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.

PURPOSE: The aim of our study was to compare in a multicentric randomized trial two regimens widely used in the treatment of advanced-stage intermediate- to high-grade non-Hodgkin's lymphoma and to assess whether a third-generation regimen (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) was superior to a second-generation regimen (procarbazine, methotrexate with leucovorin, doxorubicin, cyclophosphamide, and etoposide [ProMACE-MOPP]). PATIENTS AND METHODS: Between January 1987 and August 1991, 221 patients with diffuse intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation groups F, G, H, and K), stage II bulky (> 10 cm), III, or IV, were randomized by the Non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG) to receive ProMACE-MOPP for six cycles or MACOP-B for 12 weeks. Survival, progression-free survival, and disease-free survival were determined, and multivariate analysis of prognostic factors was performed. RESULTS: In the two groups of patients, there was no significant difference in terms of complete remission (CR) rate (49.1% with ProMACE-MOPP and 52.3% with MACOP-B), 3-year overall survival rate (45.2% with PROMACE-MOPP and 52.3% with MACOP-B), and 3-year progression-free survival rate (36.4% with ProMACE-MOPP and 36.1% with MACOP-B). In terms of toxicity, no significantly greater toxicity occurred in either arm. Overall toxicity was acceptable. The most frequent side effects were grade II through IV leukopenia, infection, mucositis, and anemia. Treatment-related deaths were equally distributed. CONCLUSION: No significant differences in terms of efficacy and/or toxicity between ProMACE-MOPP and MACOP-B are evident. These results are consistent with recent randomized trials showing that the new-generation aggressive regimens are no better than previous ones.

Adolescent↗
PubMed1994

Impact of interferon at induction chemotherapy and maintenance treatment for multiple myeloma. Preliminary results of a multicenter study by the Italian non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG).

In 1990 the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLSG) started a multicenter study on the role of interferon (IFN) in multiple myeloma (MM). The schedule of treatment was based on the assumption that melphalan plus prednisone (MP) would be better for good-prognosis patients, whereas poor-prognosis patients would benefit from polychemotherapy. Accordingly, IFN was included randomly for the induction treatment of good-prognosis patients and randomly as maintenance of the response achieved in both groups. Up to now 78 patients of the 124 enrolled have completed the induction treatment and are evaluable for response and response duration. The overall response rate was 59%. Sixty-two percent of good-prognosis patients obtained objective response, 9/14 (64%) with MP and 9/15 (60%) with MP+IFN. Up to now, with a median follow-up of 9 months from the evaluation of response, no difference has been recorded between the maintenance and no maintenance groups on relapse rate, neither in good- nor in poor-prognosis patients.

Aged↗
PubMed1991

Tumor necrosis factor-alpha and B-cell growth factor induce leukemic hairy cells to proliferate in vitro.

To clarify the mechanisms accounting for the hairy cell proliferation, in five patients with hairy cell leukemia (HCL), we evaluated the ability of neoplastic cells to proliferate in vitro in response to tumor necrosis factor-alpha (TNF-alpha), B-cell growth factor (BCGF), and interleukin 4 (IL-4). In addition, supernatants recovered from cultures of unstimulated hairy cells were tested for the capability to induce the proliferation of allogeneic hairy cells. We demonstrated that TNF-alpha and BCGF were able to induce the in vitro growth of hairy cells (stimulation index (SI) ranging, at different concentrations, from 1.6 to 10.7 and from 1.6 to 25.1 for TNF-alpha and BCGF, respectively). IL-4 did not show any proliferative effect on hairy cells. When unstimulated hairy cell supernatants were tested for the proliferative activity on allogeneic hairy cells, we demonstrated a low proliferative effect that was not inhibited by an anti-TNF-alpha antibody. Our findings demonstrate that unstimulated hairy cells proliferate in vitro in response to TNF-alpha and BCGF, thus suggesting that these cytokines could be involved in an autocrine model of cell proliferation.

Cell Division↗
PubMed1991

Different mechanisms of activation of proliferating CD3+ cells in patients with lymphoproliferative disease of granular lymphocytes.

To investigate the role of p55 and p75 chains of interleukin-2 receptor (IL-2R) on the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), the cells obtained from 11 LDGL patients (belonging to the CD3+ group) were studied for (a) the surface expression and (b) mRNA transcripts of the p55 and p75 IL-2R after activation with anti-CD3 monoclonal antibody (mAb) or interleukin-2 (IL-2). The effects of mAbs specifically blocking the p55 and p75 IL-2R on the generation of proliferative and cytotoxic functions were studied following anti-CD3 mAb stimulation. A significant difference was observed in the expression of p55 and p75 antigens on LDGL cells under resting conditions: a low number of p55 IL-2R+ (mean 1.2 +/- 0.4%) and high values of p75 IL-2R+ cells (54.9 +/- 7.4%). Accordingly, a barely detectable message for the p55 IL-2R and a strong signal for the p75 IL-2R mRNA were demonstrated. Following activation with anti-CD3 or IL-2, different patterns of IL-2R expression were observed. Anti-CD3 mAb induced an increase in the expression of the p55 IL-2R both at the mRNA and antigen level, whereas the p75 values remained consistently raised. In contrast, IL-2 induced the expression of p55 IL-2R mRNA associated with only a slight expression of this antigen. This finding was associated with a decrease in the cell expression of the p75 IL-2R, whereas the amount of p75 mRNA was unchanged. Both anti-CD3 mAb and IL-2 induced cell proliferation and cytotoxicity against the K-562 target cells. Anti-p55 IL-2R mAb did not affect the cytotoxic activity mediated by anti-CD3, but it markedly inhibited cell proliferation. Anti-p75 mAb did not inhibit either lytic function or cell proliferation mediated by anti-CD3 mAb, suggesting that only the high affinity IL-2R (p55 plus p75) is involved in anti-CD3 mediated cell activation in LDGL patients. This mechanism is different from that responsible for the IL-2 activation of CD3+ GL in LDGL patients, which is achieved through the p75 IL-2R alone. These results provide new insights into the pathophysiology of proliferating GL in LDGL patients and may also contribute to further characterization of the normal CD3+ GL population.

Adult↗
PubMed1990

Recurrent chromosomal aberrations in peripheral T-cell lymphoma.

Histological, immunological, and cytogenetic analysis of the same neoplastic tissues have been performed on seven patients with peripheral T-cell lymphomas (PTCL). Clonal chromosomal abnormalities in five cases are reported. The most common chromosomal aberration, observed in four patients, is a rearrangement of chromosome 14 with a breakpoint in q11.2. Aberrations of chromosome 8 also occurred in four patients, three of whom had an extra 8q. The data indicate that breakpoints of malignant diseases affecting similar cell types might cluster to specific chromosomal regions, which can be helpful in recognition and classification of PTCL.

Adult↗
PubMed1989

Evaluation of serum levels of soluble interleukin-2 receptor in patients with chronic lymphoproliferative disorders of T-lymphocytes.

Serum levels of soluble interleukin-2 receptor (sIL-2R) have been evaluated in 33 patients with chronic lymphoproliferative disorders of T-lymphocytes, including 12 T-helper phenotype chronic lymphocytic leukemias (Th-CLL) and 21 lymphoproliferative diseases of granular lymphocytes (LDGL). All Th-CLL cases were negative for antibodies against type I human T-leukemia virus (HTLV-I). Serum levels of sIL-2R were significantly increased in patients with Th-CLL with respect to controls (P less than 0.02) and this increase was related to the clinical course of the disease. In fact, patients with rapidly progressive disease (mean survival, 11.6 +/- 3 months) showed significantly higher concentrations of sIL-2R than patients with less aggressive disease (mean survival, 39.5 +/- 5 months) (16,223 U/ml +/- 5612 versus 1447 U/ml +/- 817; P less than 0.05). A significant positive correlation was found between sIL-2R concentrations and the number of CD4-positive cells (r = 0.64; P less than 0.05). These data point to the possible use of sIL-2R levels as a marker of active malignancy in patients with Th-CLL. Patients with LDGL showed increased sIL-2R values (721 U/ml +/- 112) with respect to controls (334 U/ml +/- 28; P less than 0.005). However, the sIL-2R levels were lower than those detected in Th-CLL patients (P less than 0.05). Among the different correlations the authors tried to establish, the only observed difference was found between serum sIL-2R levels in the group of CD3+ LDGL patients with respect to CD3- LDGL cases (P less than 0.05).

Antigens, CD↗
PubMed1989

Release of natural killer cytotoxic factor in patients with lymphoproliferative disease of granular lymphocytes.

To further investigate the mechanisms accounting for defective natural killer (NK) activity observed in the majority of patients with lymphoproliferative disease of granular lymphocytes (LDGL), we have studied the generation of natural killer cytotoxic factor (NKCF) from peripheral blood lymphocytes recovered from twelve LDGL patients. On the basis of their cytotoxic activity against the K-562 target cells, cases under study were separated in two groups. Cells from five patients, referred to as NK+, were found to exhibit high levels of NK-cell mediated cytotoxicity; cells from seven patients, referred to as NK-, despite their ability to bind to the K-562 targets, displayed a defective NK function. The coculture of cells from NK+ patients with NK sensitive K-562 cells triggered a significantly higher production of NKCF with respect to NK- patients (p less than 0.001 at 1:2 dilution). Using phytohemagglutinin (PHA) as the NKCF stimulator, differences between the groups were not significant, due to a recovery of NKCF generation in NK- patients. Furthermore, a consistent lectin (PHA) dependent cellular cytotoxicity (LDCC) was exhibited by both groups of patients. The addition of gamma-interferon (IFN-gamma) or interleukin-2 (IL-2) during NKCF generation did not significantly modify the production of this factor. Our data point out that (a) NKCF is involved in the lytic activity of LDGL patients' cells, (b) a constitutional impairment in the generation of NKCF is not present in NK- patients, since recovery of lytic function occurs after PHA stimulation, and (c) IL-2 and IFN-gamma do not play a relevant role in triggering NKCF production when added during the generation of this factor. These studies help to clarify the factors involved in the cytotoxic machinery of LDGL patients' cells, suggesting that the defect of the cytotoxic function observed in some LDGL patients could lie at the level of target recognition.

Adult↗
PubMed1987

The lymphoproliferative disease of granular lymphocytes. A heterogeneous disorder ranging from indolent to aggressive conditions.

A multiparameter analysis, which included the evaluation of clinical features, cell morphology, karyotype, phenotypic and functional immunologic findings, and T-cell receptor beta-chain configuration was performed on 34 patients with lymphoproliferative disease of granular lymphocytes (LDGL). The two-fold aim of the study was to identify the most useful tools that would more accurately characterize these patients and to deal with the problem of classifying these lymphoproliferative disorders. The data presented in this article suggest that a single parameter may not be sufficient to define the nature of the proliferating cells or to predict the clinical course of the disease and prognosis for the patient. The use of a multiparameter approach, however, may reach this goal, thus providing important prognostic and therapeutic information. Our study supports the concept that lymphoproliferative disease of granular lymphocytes is a heterogeneous disorder that ranges from indolent and possibly reactive conditions to the manifestation of aggressive malignancies.

Adult↗
PubMed1987

Interferon alfa-2b and chlorambucil in the treatment of non-Hodgkin's lymphoma.

Twenty-two patients with non-Hodgkin's lymphoma (NHL) were treated with a combined regimen of interferon alfa-2b (Intron A; Schering-Plough) and chlorambucil to evaluate the response and efficacy in pre-treated or relapsed patients. Ten patients were classified as having follicular lymphoma and 12 diffuse lymphoma. The treatment schedule consisted of interferon alfa-2b 3 X 10(6) IU/m2 thrice-weekly and chlorambucil 10 mg daily for three weeks, with a week's rest between each cycle. Treatment continued for upto six cycles. We obtained two complete remissions (CR), 12 good partial remissions (GPR), seven no remissions (NR) and one stable disease. On histologic examination we observed a response in 8 of 10 patients with follicular lymphoma (2 CR and 6 GPR); three of five patients with diffuse mixed lymphoma, and three of seven patients with diffuse lymphoma showed GPR. The major toxicity consisted of fever and nausea and, in one case, lethargy. In one patient the treatment was stopped at the second cycle because of poor compliance. Hematologic toxicity was generally mild and occurred between the third and fourth cycle. We observed hepatic toxicity i.e. a transient increase of transaminase levels, in three patients. We consider this regimen to be effective in the treatment of relapsed or resistant NHL and no more toxic than single agent therapy. A randomized study to verify this therapeutic approach versus conventional therapy with chlorambucil alone in first-line treatment is recommended.

Aged↗
PubMed1987

Cytotoxic in vitro function in the lymphoproliferative disease of granular lymphocytes.

In 20 patients with lymphoproliferative disease of granular lymphocytes (LDGL) the cytotoxic in vitro function of peripheral blood mononuclear cells was studied against both NK sensitive (K-562) and NK resistant target cells (Daudi). Cytotoxicity was analysed at resting conditions and after in vitro pre-incubation with recombinant alpha 2-interferon, gamma-interferon and interleukin 2. At resting conditions, a heterogeneous cytotoxic picture was observed against the K-562 targets, with 11 of the 20 patients showing a normal or increased NK activity, and nine an impaired function. Against the Daudi targets, unstimulated cells from all patients displayed a normal cytotoxic activity. Following in vitro stimulation, an increased lytic function against K-562 cells was demonstrated in six of the nine patients with low basal values, in three after boosting with all lymphokines tested and in three with interleukin 2. In three of these six patients incubation with interleukin 2 also produced an increased cytotoxic function against Daudi target cells; this phenomenon may be associated to the lymphokine-activated killer (LAK) system. The importance of investigating the cytotoxic in vitro function in LDGL patients to further characterize the biological features of GL and its relevance to better define the nature of this disease are discussed.

Adult↗
PubMed1986

Preliminary observations on intravenous idarubicin (4-demethoxydaunorubicin) in the chronic and accelerated phase of chronic myelogenous leukemia.

The study included 13 patients with chronic myelogenous leukemia (8 in the chronic phase with high WBC counts at onset, and 5 in the accelerated phase, poorly responding to conventional drugs for the chronic phase). They were treated with 4-demethoxydaunorubicin (idarubicin), a new anthracycline analog more active than daunorubicin (DNR) and doxorubicin (DX) in experimental tumor models which offers a higher therapeutic index than existing anthracyclines. Idarubicin was administered i.v. at the dose of 8 mg/m2 on days 1, 3 and 5. All patients in the chronic phase (8/8) developed significant leukopenia. Five of these 8 patients showed complete reduction of splenomegaly, and 4 of hepatomegaly as well. In all the other cases, hepato-splenomegaly was reduced by more than 70%. Three of the 5 patients in the accelerated phase of chronic myelogenous leukemia also showed massive cytolysis. More important, all of them showed complete or major reduction of hepato-splenomegaly and renewed responsiveness to conventional drugs for the chronic phase of the disease. Idarubicin was fairly well tolerated by all patients with only minor gastrointestinal side effects and no liver damage or acute cardiotoxic effects. These findings indicate that idarubicin--although it cannot replace established drugs for the chronic phase of the disease--represents an added therapeutic resource for producing rapid cytolysis at onset and, above all, in the accelerated phase of chronic myelogenous leukemia.

Administration, Oral↗
PubMed1986

The analysis of expanded cells from patients with lymphoproliferative disorders of granular lymphocytes may help to clarify the NK cell differentiation.

Surface phenotype and functional in vitro activities were studied in 2 cases of lymphoproliferative disorders of granular lymphocytes. Cells from both patients presented the same, previously unreported, surface phenotype (i.e. T3+, T8+, T4-, HNK-1-, NK-15+, M1-), were unable to display either Natural Killer (NK) activity or suppressor function in a poke-weed-driven system, and showed a defective response to phytohemagglutinin (PHA). On the basis of available schemes for NK cells ontogenesis, we will discuss the phenotype and functional activities of patients' cells suggesting that the cell population expressing the T3+, T8+, HNK-1-, NK-15+, M1- phenotype might represent a discrete stage along the NK-cell differentiation pathway.

Antigens, Surface↗