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Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 325 records · Page 18Linked to original sources
PubMed1989

CD7 positive acute myeloid leukaemia: a subtype associated with cell immaturity.

Seventeen patients with acute myeloid leukaemia (AML) whose blasts co-expressed the T-cell associated CD7 antibody were identified among 160 consecutive AML cases. Fourteen had FAB defined AML according to morphocytochemical criteria, whereas three patients were classified as 'MO' on the basis of immunophenotype. The incidence of CD7 positively was particularly significant in the less differentiated subtypes M0 and M1 compared with other FAB groups (P less than 0.001). In all cases the myeloid determinants CD13 and/or CD33 were associated with CD7 expression. Other B-lymphoid (CD10, CD19) or T-lymphoid (CD2, surface and cytoplasmic CD3) markers were analysed and found to be negative. Five out of 15 cases examined were TdT+. Clonal rearrangements of the immunoglobulin heavy chain (IgH) and/or T-cell receptor (TcR) beta chain genes were identified in only three out of 13 cases. Among these, one out of five co-expressing TdT showed IgH rearrangement when analysed at the DNA level. Clinical features at presentation and response to induction therapy did not allow us to consider CD7+ AML patients as a distinct subgroup with prognostic significance. Our data indicate that CD7 expression is a common finding in immature AML, being generally found in the absence of other T-cell features. Rather than suggesting the occurrence of 'mixed leukaemia', such cases confirm a broader spectrum of CD7 reactivity and its possible identification of a particular subset of myeloid progenitors.

Antigens, CD7↗
PubMed1989

Waldenström's macroglobulinaemia: results of a combined oral treatment in 34 newly diagnosed patients.

From February 1978 to September 1987, 34 patients with Waldenström's macroglobulinaemia (WM) were treated using an oral combination consisting of melphalan (6 mg m, days-2 1-7) cyclophosphamide (125 mg m-2, days 1-7) and prednisone (40 mg m-2, days 1-7). Courses were repeated every 4-6 weeks for a total of 12 courses. After the completion of 12 courses, responding patients received continuous treatment with chlorambucil (3 mg m-2 d-1) and prednisone (6 mg m-2 d-1) until relapse. Following the induction, 23 of 31 evaluated patients (74%) have responded to induction therapy of whom eight (26% of the 31 evaluated patients) achieved complete remission defined as disappearance of all clinical and laboratory features characteristic of WM. The overall median response duration, as of December 1988, has not yet been reached, while the overall median event-free survival duration for the entire population and for responding patients is 66 months in both groups. However, in responding patients the event-free survival duration after 66 months reaches a plateau. Toxicity was limited to transient nausea and vomiting (grade 2 according to WHO). In conclusion, this study demonstrates the efficacy and safety of an oral polychemotherapeutic treatment in the management of Waldenström's disease.

Cyclophosphamide↗
PubMed1989

Intermediate-dose (25 mg/m2) intravenous melphalan for patients with multiple myeloma in relapse or refractory to standard treatment.

Intermediate-dose (25 mg/m2) intravenous melphalan has been evaluated in 34 multiple myeloma patients refractory to standard chemotherapies. The median time from diagnosis to entering of patients into the study was 27 months (range 7-71 months). A response was obtained in 12/34 patients (35%). 4 of 12 responding patients have relapsed and 2 of these have died; 8 responders have not relapsed and are still alive. The median duration of survival after 28 months of follow-up has not yet been reached in the group of patients responding to treatment. However, the overall median duration of survival for the 34 patients entered into the study was 8 months. The median duration of response was 16 months. Toxicity was limited to leukopenia, thrombocytopenia, nausea and vomiting. This lack of severe toxicity allowed us to administer the drug on an outpatient basis. The response rate and the low toxicity observed in this group of patients are encouraging and suggest that intermediate-dose intravenous melphalan is an effective and safe second line treatment for patients with multiple myeloma not responding to conventional treatment.

Female↗
PubMed1989

High-dose Ara-C (HiDAC) plus asparaginase in elderly patients with acute non-lymphocytic leukemia: a pilot multicentric study by the Italian Cooperative Group GIMEMA.

A multicentric prospective pilot study using three different schedules of high-dose Ara-C at dosage of 3 g/m2 every 12 hours during 3 h of infusion was undertaken by the Italian Cooperative Group GIMEMA in order: 1. to evaluate the safety and efficacy of such treatment in previously untreated ANLL patients more than 50 years old; 2. to investigate whether the addition of a standard maintenance treatment after consolidation with 4 courses of DAT (Daunorubicin + Ara-C + 6-Thioguanine) could improve the duration of complete remission (CR) and the proportion of long-term survival. Overall 43/125 evaluable patients (34.4%) achieved CR. 32/125 died during the induction phase, the remaining 50 patients (40%) failed to achieve CR. As for the toxicity, the most significant toxicity of all schedules was hematologic. No substantial neurological or cardiac toxicity was observed. The multivariated analysis of several pretreatment characteristics revealed that age more than 60 yr, male sex and presence of infections at diagnosis were the most significant adverse factors for achievement of CR. The median duration of DFS for all responders was 9 months, with relapse-free survival at 4 yr estimated at 29%. The addition of maintenance treatment to consolidated patients had no advantages in respect to the control group, even though the statistical analysis revealed a p = 0.058. However, because of the small number of randomized patients, no conclusions can be drawn concerning the importance of maintenance treatment.

Aged↗
PubMed1989

Prolonged effect of alpha-interferon after discontinuance of treatment in chronic myelogenous leukemia patients.

14 patients out of a group of 73 affected by CML and treated with alpha-2-IFN, who had obtained hematological and cytogenetic response, were selected to be submitted to autologous BMT. In all patients the IFN treatment was interrupted to obtain an increase of the peripheral WBC necessary for its collection by means of leukapheresis. After a median time of 20.5 weeks from discontinuance of therapy, most patients are still under hematological disease control. Serially performed cell cultures have shown deeply and persistently reduced growth patterns; cytogenetic analyses have displayed Ph' mosaicism, but with a progressive increase in time of Ph' + cells. Such findings reveal that the effect of alpha-2-IFN in CML patients can be unexpectedly prolonged after discontinuance of treatment. A possible explanation might be found in the complexity of the biological mechanisms of action of IFN, thus giving this drug promising therapeutic prospects in the treatment of CML.

Adult↗
PubMed1989

Acute myelogenous leukemia in first relapse treated with two consecutive autologous bone marrow transplantations: a pilot study.

The feasibility and the antileukemic activity of a double sequential autograft has been evaluated in 3 patients affected by AML in first hematological relapse. Bone marrow collection and cryopreservation was performed twice: during first complete remission (CR) and during second CR. At the time of relapse patients underwent first ABMT with BAVC preparative regimen achieving a second CR without any remarkable complications. After 4, 5 and 4 months respectively a second ABMT was performed with a different preparative regimen, consisting of cyclophosphamide and fractionated total body irradiation (Cy + F-TBI). A delay in platelet recovery was observed after the second procedure as compared to the first, while neutrophils recovery was comparable. 1 patient died in CR (on day +91 after second ABMT) of interstitial pneumonitis. 2 patients are alive and well without evidence of disease after 46 and 53 months of unmaintained second CR. This experience shows the high antileukemic potential of treatment with a double sequential autograft; 2 relapsed patients in fact are long-term survivors with a second CR longer than the first.

Adult↗
PubMed1989

Deficiency of lymphocyte lectin-dependent cytotoxicity in myelodysplastic syndromes.

We studied a group of patients with myelodysplastic syndromes (MDS) for surface markers and cytotoxic activities of peripheral blood mononuclear cells (PBMNC). The results indicate a significant increase in the total count of CD11b+, Leu7+ and CD16+ with a percent reduction in CD4+. A reduction in PHA-induced cellular cytotoxicity (PHA-ICC) and NK activity were found. A similar phenotype was found both in refractory anemia (RA) and (RA) with excess of blasts (RAEB/RAEB-t). However, the functional activities reached the normal level only in RA patients; while in RAEB/RAEB-t patients a significant reduction was detected in PHA-ICC and NK activity.

Aged↗
PubMed1989

Response to pentostatin in hairy-cell leukemia refractory to interferon-alpha. The European Organization for Research and Treatment of Cancer Leukemia Cooperative Group.

Interferon-alpha (IFN-a) or 2'-deoxycoformycin (pentostatin; DCF) have each been shown to be highly active in hairy-cell leukemia (HCL). In this phase II study of the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC), the efficacy and toxicity of DCF were investigated in patients who were resistant to IFN-a treatment. Resistance was defined as: (1) progressive disease (PD) under IFN-a therapy for more than 2 months; (2) stable disease (SD) after more than 6 months of IFN-a treatment; (3) relapse within 3 months of discontinuing IFN-a; and (4) intolerance to IFN-a because of World Health Organization (WHO) grade 3 or 4 toxicity. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Responders were given a maintenance therapy once per month for a maximum of 6 months. At the time of report, 33 patients with resistant disease were evaluable for response and toxicity. Median duration of IFN-a therapy before DCF administration was 14.7 months (range, 1 to 41 months). Complete remissions (CRs) were achieved in 11 patients and partial remissions (PRs) in 15, resulting in a total response rate of 78.8%. Median interval between beginning of DCF therapy to best response was 3.9 months with a range from 2.0 to 7.0 months. Two patients who achieved PR have relapsed 7 and 14 months after cessation of DCF therapy. The median duration of response was over 11.5 months (range, over 3.0 to over 24.0 months). Three patients died within the first 6 weeks of DCF treatment: one of drug-unrelated cardiomyopathy and two of fungal pneumonia. The patients with early death (n = 3) and nonresponsive disease (n = 4) received IFN-a treatment for a longer period (median, 18.0 months) than did the 26 responsive patients (median, 10.0 months). Major side effects included nausea, skin rash, and infections and were otherwise mild. Thus, DCF is highly active in patients with HCL resistant to IFN-a.

Adult↗
PubMed1989

Autologous bone marrow or peripheral blood stem cell transplantation for patients with chronic myelogenous leukaemia in chronic phase.

The progressive and fatal course of chronic myelogenous leukemia has not been affected significantly by chemotherapeutic agents that control the benign phase of the disease. Combination chemotherapy and aggressive treatments may offer some advantages: however, these approaches do not appear to produce stable suppression of Ph1 chromosome or to prolong chronic phase and survival of these patients. Only allogeneic bone marrow transplantation has been demonstrated to be capable of inducing a stable, complete suppression of Ph1+ cells. Recently alpha Interferons (IFN) have been shown to control myeloid proliferation in patients with CML and to determine a progressive and persistent decline of Ph1+ bone marrow cells in some cases. The hypothesis that in most newly diagnosed patients with CML various amount of Ph1 negative cells must still be present, albeit in suppressed state in the bone marrow (BM) or in the peripheral blood (PB), have led some Authors to treat patients with high-dose chemotherapy followed by reinfusion of stem cells collected at diagnosis or after a response to cytoreductive treatments. We report 34 patients with CML treated in chronic phase with Busulohan and Melphalan conditioning regimen followed by reinfusion of BM or PB stem cells.

Adult↗