Search PubMed⌕ Search

Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 271 records · Page 15Linked to original sources
PubMed1991

Peripheral blood and bone marrow immunophenotypic and functional modifications induced in acute leukemia patients treated with interleukin 2: evidence of in vivo lymphokine activated killer cell generation.

The effect of treatment with interleukin 2 (IL2) on the phenotypic and functional immune system of acute leukemia patients was investigated. Fifteen acute myeloid leukemia and acute lymphoid leukemia patients with evidence of persistent disease were further subdivided into two groups according to the percentage of bone marrow (BM) blasts: group a had 6-15% blasts and group b had 30-65%. Following two cycles of IL2 (Glaxo Imb, Geneva, Switzerland) given i.v. by continuous infusion at escalating doses, no major changes in the proportion of CD3-, CD4-, and CD8-positive cells were encountered in the blood or in the marrow of either group of patients. When these could be retested after four cycles of IL2, a significant increase of CD3+ and CD4+ cells was documented in the peripheral blood (PB), as well as a significant increase of CD3+ cells in the BM. Irrespective of the number of cycles administered, the proportion of CD16+ cells increased significantly in the blood in both groups of patients and in the marrow of group a patients only. The expression of CD25 was significantly enhanced in all samples tested. Following IL2 administration, an enhancement of the natural killer compartment was documented. This was consistently more evident in patients with more limited disease. A significant amplification of the in vitro-induced lymphokine-activated killer function was noted in the BM of the treated patients. Furthermore, we documented the presence both in the PB and in the BM of "spontaneous" lymphokine-activated killer cells generated in vivo following IL2 administration. These results demonstrate that in acute leukemia of both myeloid and lymphoid origin, treatment with IL2 is capable of inducing profound immunophenotypic and functional modifications in PB and in BM lymphocytes, particularly in patients with more limited disease. The evidence of the in vivo activation of cytotoxic cells, particularly in the BM, may help to explain the clinical responses preliminarily observed in individual acute leukemia patients.

Acute Disease↗
PubMed1991

CD9 antigen on acute non-lymphoid leukemia cells: preferential expression by promyelocytic (M3) subtype.

A monoclonal antibody (S17-12), previously described to recognize subsets of myelomonocytic cells, is demonstrated to bind CD9 antigen, a surface marker of B-cell precursors, platelets and several non-hematopoietic tissues. The proportion of S17-12, CD9-positive leukemic cells was determined in 102 patients with acute non-lymphocytic leukemia. It was found to be above 75% in 14/22 M3 cases (including 3/3 of microgranular variant) and only in 1/80 cases of different FAB subtype. Complete reactivity (greater than 95%) of leukemic clonogenic cells with CD9 MoAB was restricted to 4/18 M3 cases. Therefore, a high proportion of CD9-positive cells seems to be peculiar to M3 cases. This may help in the diagnosis of cases that lack typical morphological features.

Antibodies, Monoclonal↗
PubMed1991

A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA.

255 patients with acute non-lymphoid leukaemia (ANLL), observed between October 1984 and June 1987, entered a chemotherapy regimen consisting of induction therapy with cytarabine in combination with idarubicin (IDA/ARA) or daunorubicin (DNR/ARA), followed by consolidation with four courses of IDA + ARA plus 6-thioguanine (6-TG) or DNR + ARA + 6-TG and a 6 month maintenance therapy with 6-TG and ARA. The median age was 62 years (range 55-78 years) and 33 were aged more than 70 years. The treatment groups were comparable for median age, FAB type, performance status and initial blood counts. 249 patients were randomised, 124 to the IDA/ARA arm and 125 to the DNR/ARA arm. Complete remission was achieved in 50 patients (40%) on the IDA/ARA treatment program and 49 patients (39%) on DNR/ARA. No definite differences were found between patients receiving IDA/ARA and those treated with DNR/ARA as far as complete response (CR), overall survival, failure free and relapse free survival are concerned. 74% of the complete responders in the IDA/ARA arm and 51% in the DNR/ARA arm achieved CR after a single course of treatment. Resistant leukaemia was observed in 13.7% of the patients in the IDA/ARA arm and in 31.2% in the DNR/ARA one, whereas hypoplastic death occurred in 29% and 14.4%, respectively. In conclusion, our data failed to show any advantage of idarubicin over daunorubicin even though there is some evidence that IDA, despite the higher toxicity, is more rapid in eradicating leukaemia as proved by the higher CR rate obtained after one course of induction.

Aged↗
PubMed1991

The F-MACHOP sequential combination chemotherapy regimen in advanced diffuse aggressive lymphomas: long-term results.

The present study reports the long-term results of the F-MACHOP sequential combination chemotherapy regimen in 113 adult patients with advanced stages of diffuse large-cell or undifferentiated lymphoma who were consecutively treated with this regimen from January 1980 to December 1986 at a single institution. The CR rate was 78% and 17 relapses were observed, so that 80% of CR patients are expected to be free of relapse at 5 and 10 years after a median follow-up off-therapy of 5.7 years (range 3.2-10.1). Projected survival and event-free survival at 8 years are 68% and 62%, respectively. Prognostic factor analysis indicates that the CR rate was influenced by systemic symptoms and number of extranodal sites, disease-free survival by tumor burden and number of courses to achievement of CR, event-free survival and survival by tumor mass diameter, systemic symptoms and number of extranodal sites. Toxicity was mainly hematological, and 3 patients (3%) died while severely neutropenic. The rapidity of response appears to have prognostic value, particularly in patients presenting with high tumor burden, in whom achievement of a CR within 3 courses indicates a group of patients with a very high chance of cure with this regimen.

Adolescent↗
PubMed1991

Epidemiology of acute promyelocytic leukemia in Italy. APL Collaborating Group.

This retrospective epidemiologic study on 256 cases of Acute Promyelocytic Leukemia (APL) observed in 20 Italian hematology centers between 1980 and 1988 demonstrated that APL is different from the other acute non-lymphocytic leukemias (ANLL). The male/female ratio was 0.9; median age at diagnosis was 40 years (with 80% of patients between 15 and 54 years of age). The minimal annual incidence of APL in Italy per 1,000,000 inhabitants was estimated to be 0.6; an increased incidence was observed in spring and in autumn. The overall median survival duration of APL patients was 12.6 months. From an epidemiological point of view APL is a distinctive subtype of ANLL.

Adolescent↗
PubMed1991

Is interferon alpha in cutaneous T-cell lymphoma a treatment of choice?

This study was designed to evaluate the therapeutic efficacy and toxicity of recombinant interferon alpha-2a (rIFN alfa-2a) given as initial systemic therapy in untreated mycosis fungoides and/or Sezary's syndrome patients, at a slowly escalating schedule up to the maximal tolerated dose. At the same time this schedule was administered in patients who had relapsed or were refractory to previous treatment; 28 newly diagnosed and 15 previously treated patients entered the study. IFN was given daily with dose escalation from 3 to 18 MU. The last follow-up in June 1990 indicates that 90% of previously untreated patients who obtained a complete remission remain in continuous complete remission after 18 to 40 months and that 75% of previously untreated patients who obtained partial remission remain in partial remission after 20-44 months. The event-free survival projected, calculated using the Kaplan and Meier product limit technique, was 21% of all patients at 54.7 months (40% in the previously untreated groups and 14% in the previously treated group: P = 0.12). In conclusion, interferon is very effective as a single agent in cutaneous T-cell lymphomas.

Adult↗
PubMed1991

Treatment of acute myeloid leukaemia patients with recombinant interleukin 2: a pilot study.

Twelve patients with acute myeloid leukaemia (AML) with evidence of resistant disease were treated with recombinant interleukin 2 (rIL2) given intravenously by continuous infusion. No objective response to rIL2 alone was documented in the seven patients with advanced disease (20-90% resistant blasts in the marrow), except for a partial response to rIL2 plus chemotherapy in one. Of the five patients with limited disease (8-15% marrow blasts), three obtained a complete disappearance of the blasts following two to four 5d courses of rIL2 alone. One patient persists in fourth complete remission (CR) 30 months later, another obtained a third CR for 4 months, and the last remained in third CR for 9 months before relapsing. This latter patient achieved a fourth CR with low-dose cytarabine. The remissions have been maintained with low-dose monthly courses of rIL2 given on an out-patient basis. Two AML did not respond to rIL2 alone; one, however, obtained a fourth CR with chemotherapy and rIL2. Administration of rIL2 was accompanied by organomegaly and leucocytosis, with a frequent lymphocytosis and increase in eosinophils and large granular lymphocytes, both in the blood and in the marrow. Side effects, though often severe, were controllable using a daily dose escalating protocol and never required intensive care treatment. The results of this pilot study indicate that treatment of AML patients with rIL2 is feasible and may result in the disappearance of chemotherapy-resistant blasts in patients with limited but detectable disease. Further controlled trials in AML in CR appear warranted.

Acute Disease↗
PubMed1991

Chronic myeloid leukaemia lymphoid blast crisis. Relevance of molecular analysis at the bcr and immunoglobulin heavy chain gene level in monitoring response to therapy and residual disease.

Southern blot analyses were performed in sequential DNA samples from 4 patients with Ph' + chronic myeloid leukaemia (CML) who underwent lymphoid or mixed blast crisis (BC). Genomic rearrangements at the breakpoint cluster region (bcr) and immunoglobulin heavy chain (IgH) gene level provided, in these cases, a sensitive and specific evaluation of response to therapy both in terms of blasts and Ph' + cell suppression. Recurrent BC was molecularly characterized in the 4 patients, showing each time identical individual specific DNA rearrangement patterns. Residual blasts were detected in 2 cases during intervening chronic phases by IgH rearrangements. Such findings highlight the specificity of these molecular markers, clearly indicating the failure of ablative therapy in eradicating the neoplastic clone. Finally, molecular and phenotypic identity in individual recurrent BC also suggested, in our cases, a lack of clonal evolution during disease progression.

Antineoplastic Agents↗
PubMed1991

Studies of von Willebrand factor in essential thrombocythemia patients treated with alpha-2b recombinant interferon.

The crucial role of the von Willebrand Factor (vWF) and its interaction with platelets in myeloproliferative disorders (MPD) have emerged in recent years. Recently, many authors have reported the therapeutical efficacy of interferon (IFN) in MPD with thrombocytosis in decreasing platelet number. The purpose of our report is to study the modifications of vWF in a series of 20 patients affected by essential thrombocythemia (ET) or MPD with thrombocytosis, treated with alpha 2b recombinant IFN (alpha 2b-rIFN). Patients were studied before treatment and after complete or partial response: vWF-related properties, bleeding time (BT) and ristocetin-induced platelet aggregation (RIPA) were evaluated. Before treatment, we found prolonged BT in 5 patients (25%), abnormal RIPA in 8 (40%), reduced factor VIII coagulant activity (VIII:C) in 2 (10%), reduced vWF-related antigen (vWF:Ag) in 5 (25%) and low vWF:ristocetin cofactor (vWF:Ricof) in 5 (25%). Twelve subjects were evaluated after hematologic remission: in all patients, BT, VIII:C, vWF:Ag and vWF:Ricof were within normal range or upper normal limits. RIPA was abnormal in 7 subjects. Multimer patterns of vWF were performed in 3 patients before and after treatment: 2 of them showed loss of high-molecular-weight multimers that seemed to recover at remission. IFN seems to induce improvement of platelet number and their functions in MPD with thrombocytosis.

Adult↗
PubMed1991

Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia.

Thirty-two patients with refractory acute myeloid leukemia (AML) received salvage therapy with a single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 IV for a period of 1 hour, and cytarabine (Ara-C) 1 g/m2 IV for a period of 6 hours daily for 6 days (MEC). Eighteen patients were primarily resistant to conventional daunorubicin and Ara-C induction treatment; eight patients had relapsed within 6 months from initial remission; six patients had relapsed after a bone marrow transplantation (BMT) procedure. Overall, 21 patients (66%) achieved a complete remission (CR), two (6%) died of infection during induction, and nine (28%) had resistant disease. Age greater than 50 years was the only factor predictive for a significantly lower response rate (P = .03). The median remission duration was 16 weeks; the overall median survival was 36 weeks. Severe myelosuppression was observed in all patients resulting in fever or documented infections in 91% of patients. Nonhematologic toxicity was minimal. We conclude that the MEC regimen has significant antileukemic activity and acceptable toxicity in salvage AML. Its benefit in front-line AML therapy is being investigated.

Adolescent↗
PubMed1991

MACOP-B vs F-MACHOP in the treatment of high-grade non-Hodgkin's lymphomas.

From September 1988 two hundred-sixty-seven (267) untreated patients (pts) with stage II to IV high grade non Hodgkin's lymphoma (NHL) have been enrolled in a multicenter, randomized, still ongoing study, comparing two third-generation combination chemotherapy regimens, MACOP-B versus F-MACHOP. At the present time, 177 pts have completed the treatment program and are evaluable, with a median follow-up of 13 months. Clinical, histologic and laboratory characteristics are equally distributed in both groups. Among the 92 pts treated with MACOP-B, 58 (63%) achieved a complete remission (CR), 17 complete responders have relapsed (29%), and 21 have died (23%), including 3 treatment-related deaths. Among the 85 pts who received F-MACHOP, 65 (76%) achieved a CR, 9 complete responders have relapsed (14%), and 11 pts have died (13%), including 3 treatment related deaths. 30 months-projected survival is 64% for MACOP-B treated pts compared to 84% for F-MACHOP treated pts; 30 months-projected relapse- free survival is 80% and 84%, respectively. F-MACHOP seems to be superior in immunoblastic lymphoma (overall survival, OS, 82% vs. 54%) and in Burkitt-type lymphoblastic lymphoma (OS 100% vs, 42%). The degree of hematological and non-hematological toxicity was similar in both regimens. More reliable conclusions will be drawn after a longer follow-up.

Adult↗