Search PubMed⌕ Search

Biomedical subjects

E Pogliani

Publications and source records attributed to E Pogliani.

At least 37 records · Page 2Linked to original sources
PubMed1997

Interleukin-2 therapy in relapsed acute myelogenous leukemia.

PURPOSE: Several studies have been conducted in Italy to assess the activity of recombinant interleukin-2 (rIL-2) in patients with relapsed-refractory acute myelogenous leukemia (AML) and in AML patients in second complete remission (CR) who are not eligible for standard therapy. We report here the updated results of those studies. PATIENTS AND METHODS: Since 1988, a total of 24 patients with relapsed-refractory AML and < or = 30% bone marrow blasts (median blastosis, 15%), who were not suitable for further chemotherapy, were treated with a daily dose-escalating protocol of rIL-2 (8-18 x 10(6) IU/m2 x 5 days) by continuous intravenous infusion with a 72-hour rest period between each cycle. Patients achieving a response to induction therapy received subcutaneous maintenance rIL-2 therapy at lower doses for 5 days/month. Based on these encouraging results, a prospective randomized trial was initiated by the Italian cooperative groups GIMEMA (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto) and AIEOP (Associazione Italiana Ematologie e Oncologia Pedietrica) to assess the efficacy of this rIL-2 regimen in AML patients in second CR. Of 264 AML patients enrolled, 146 patients (55%) achieved a second CR in response to mitoxantrone, etoposide, and cytarabine; 32 patients who were not eligible for transplantation were randomized to rIL-2 (15 patients) or no treatment (17 control patients). Accural goals were never reached, however, due to low recruitment. RESULTS: In the pilot study, 13 patients (54%) obtained a CR, which persists in eight patients with a median follow-up of 64 months (range, 1-110 months) on maintenance rIL-2. In the randomized study, a trend in favor of improved disease-free survival was observed in the rIL-2 arm. CONCLUSIONS: Encouraging results have been obtained with rIL-2 therapy in AML patients with relapsed-refractory disease and limited blastosis and in patients in second CR. These results have prompted a large, multicenter, randomized study to evaluate the efficacy of high-dose rIL-2 therapy in AML patients with advanced disease but limited blastosis in relapse following cytoreductive chemotherapy or autologous transplantation.

Adolescent↗
PubMed1996

Age-adapted moderate-dose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia.

We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.

Aged↗
PubMed1996

Molecular diagnosis and clinical relevance of t(9;22), t(4;11) and t(1 ;19) chromosome abnormalities in a consecutive group of 141 adult patients with acute lymphoblastic leukemia.

Over a time period of five years leukemic blast samples from 141 consecutive patients with adult ALL were referred to our laboratory, for molecular evaluation of chromosome abnormalities. The t(9;22), t(4;11) and t(1;19) which are most commonly found in adult ALL with a B-precursor phenotype were molecularly analyzed by similar RT-PCR based protocols. BCR-ABL transcripts generated by the t(9;22) translocation were demonstrated in 36 patients (25%) and were restricted to the 109 patients with B precursor ALL (33% of this group). Of 83 patients showing a, common phenotype (CD10+), 34 were BCR-ABL positive (41%) whereas only 2 out of 26 with Null ALL (HLADr+, CD19+, CD10) were positive. Interestingly, the percent of BCR-ABL positive CD1O+ ALL increases significantly with age being 20% in patients less than 30 years old and more than 50% in older patients. None of the T-ALL (24 patients) and B-ALL (8 patients) were positive. The majority of cases (67%) showed the p190 gene subtype. The cytogenetic diagnosis of Philadelphia chromosome was always confirmed by the molecular analysis and this approach allowed for the detection of the presence of the BCR-ABL rearrangement in 26 patients when a negative result or no metaphases were obtained. The complete remission rate was similar among BCR-ABL positive and negative patients but a shorter remission duration was observed in those showing molecular evidence of t(9;22) and this finding was significantly evident in CD1O+ ALL patients. By means of comparison, in most of the same adult ALL patients, we analyzed the yet unrecognized prevalence of the t(4;11) and t(1;19) translocations by the molecular analysis of their chromosomal breakpoints. Rearrangements of the ALL-1 gene on 11q23 band and ALL- l1AF.4 fusion transcripts specific for the t(4;11) were demonstrated in 7 out of the 21 Null ALL investigated, with no additional positive cases found among the other ALL subgroups. Overall the clinical behavior of t(4; 11) positive patients was dismal with a very short CR duration. Chimeric E2A-PBX1 transcripts generated by the t(1;19) were found in only two of the 87 B-precursor ALL analyzed. The presented results provide further evidence for the utility of RT-PCR based methods for the molecular diagnosis of chromosome translocations in ALL. The identification of such abnormalities can significantly contribute to the identification of more appropriate therapeutic options for standard and high risk ALL patients

Adolescent↗
PubMed1996

The role of anthracyclines in adult acute lymphoblastic leukaemia.

The role of anthracyclines (ANT) in the treatment of adult acute lymphoblastic leukaemia (ALL) is poorly defined as regards drug dosage, schedule, preferable compound, and indications for use in specific treatment phases or disease subset. We therefore reviewed ANT treatment results in adult ALL. Altogether, an early and intensive use of ANT would improve both initial response rate and long-term disease-free survival; idarubicin (IDR) exhibits a considerable antileukaemic activity deserving further evaluation as possible reference drug; and the prognosis of CD10+ t(9;22)/BCR-ABL- ALL can be particularly good following an early dose-intensive ANT consolidation program.

Adolescent↗
PubMed1996

Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-alpha hybrid protein by lymphocytes of acute promyelocytic leukemia patients.

In previous studies, it was shown that the fusion region of the pml/RAR-alpha protein, expressed by acute promyelocytic leukemia (APL) cells, can be specifically recognized in vitro by donor (D. E. ) CD4 T cells in a HLA class II DR11-restricted fashion. We present here the results on the recognition of several pml/RAR-alpha peptides by APL patients expressing HLA DR11. The in vitro immunization of peripheral blood lymphocytes from four patients in remission (S. R., F. R., M. M., P. G.) with BCR1/25, a 25-mer pml/RAR-alpha, did not elicit either a polyclonal or a clonal immune response specific to the peptide. We then generated new donor anti-pml/RAR-alpha CD4(+) T-cell clones. These clones were tested for their recognition of BCR1/25. One clone (C3/5, CD3(+), CD4(+), CD8(-)) was selected for further analysis. Clone C3/5 showed specific proliferation, cytotoxicity, and cytokine (tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25. C3/5 cells developed specific proliferation and cytotoxicity when challenged with peptide-pulsed lymphoblastic cell lines and peripheral blood lymphocytes from the four DR11(+) APL patients. APL blasts, available only from patients F. R. and P. G., were not lysed by C3/5 and were unable to present peptide BCR1/25. Incubation of APL cells with IFN-gamma failed to induce HLA class II molecules and recognition by the C3/5 clone. Since APL cells do not express HLA class II molecules, we tested in two donors (D. E. and C. H. R.) and in patients S. R. and P. G. whether the use of 9-mer peptides (BCR1/9) would generate a CD8/HLA class I-restricted response. No peptide-specific T-cell line or clone could be generated from both donors and patients. These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL.

Binding Sites↗
PubMed1994

Association therapy as a prognostic factor in deep fungal infection complicating oncohaematological diseases.

A group of 31 oncohaemopathic patients (17 male, mean age 44 +/- 6 years), diagnosed as having primary deep fungal infection involving the lungs, were retrospectively evaluated. When infection was suspected on a clinical basis the major associated risks for death were the duration of bone marrow aplasia (12 +/- 7 versus 21 +/- 6 days, P < 0.001), increase in white blood cells and, in particular, prolonged granulocytopenia (11 +/- 5 versus 24 +/- 8 days, P < 0.001) when survivors were compared with patients, who died. Our therapeutic empirical approach was based on the association of i.v. amphotericin B, 1 mg kg-1 day-1, with oral 5-fluorocytosine (5-FC) 150 mg kg-1 day-1. Only 9 subjects received combination therapy for more than 7 days. For majority of them, oral 5-FC was interrupted because of altered compliance or sustained liver damage. A chi 2 test for independent parameters showed (P = 0.0021) a concentration of deaths among patients who received amphotericin B alone (15/22); none of the patients treated with amphotericin B + 5-FC (9 cases) died. Results generally suggest that a more favourable outcome was statistically associated with empirical antifungal combination therapy in deep fungal infection, although both treatment regimens showed effectiveness in terms of survival. Nevertheless the low 5-FC compliance and the small sample do not indicate the safe use of this drug in a large population.

Adolescent↗
PubMed1994

Effects of recombinant human stem cell factor (rh-SCF) on colony formation and long-term bone marrow cultures (LTBMC) in patients with myelodysplastic syndromes.

Stem cell factor (SCF), the ligand of the c-kit receptor, is a potent enhancing cytokine for haematopoietic cells in the presence of IL-3, GM-CSF and erythropoietin (Epo). In the clonogenic assays of 63 MDS patients, the addition of rh-SCF + GM-CSF and/or IL-3 induced a significant increase (p < 0.001) in the number and size of CFU-GM. Never reaching the levels of controls, this increase was seen in all FAB subtypes, but particularly in RA. There was no significant increase in cluster formation, even in RAEB or RAEBt. Rh-SCF (10 ng/ml) led to mean increases of up to 26 times in the number of Epo-dependent BFU-E colonies, particularly in RA (p < 0.001) and RAEB (p < 0.05). Individual responses varied widely (especially in RA) from no response to supranormal levels. Added to the weekly refeed of 37 MDS LTBMC, SCF (10 ng/ml) induced only a 7% mean increase in both cell output and the number of clonogenic cells recovered in the supernatant. Immunohistochemical examination of the supernatant showed significant increases in differentiating myeloid cells in all examined cases, and in erythroid cells in 3 cases; blast cells increased in only 3 cases. These data suggest that rh-SCF is capable of at least partially reversing defective MDS myeloid haematopoiesis, and leads no overt risk of leukaemic transformation. Its potent effect on erythroid cells is encouraging for future clinical applications in patients, particularly if they are selected by means of in vitro tests.

Bone Marrow Cells↗
PubMed1993

Preliminary study to identify cancer patients at high risk of venous thrombosis following major surgery.

This study investigated whether the pre-surgical plasma levels of TAT and F1 + 2 of patients undergoing major surgery for localized tumours could identify patients at higher risk of thrombosis, and how heparin prophylaxis affected in vivo coagulation after cancer surgery. We measured the pre- and post-operative levels of TAT, F1 + 2, total factor VII (FVIIt) and zymogen FVII (FVIIz) in 117 cancer patients, with and without heparin prophylaxis. The end points of this study were DVT, initially detected by 125I-fibrinogen uptake test and confirmed by ascending venography. Pre-operative [TAT] and [F1 + 2] of the cancer patients were significantly higher than those of age-matched control subjects (n = 50) (P < 0.005 and P < 0.05, respectively); pre-operative [FVII] was not significantly different. One of the 83 patients receiving prophylaxis, and 8/34 not receiving prophylaxis developed post-operative DVT. Of the parameters evaluated, only the pre-operative [TAT] > 3.5 ng/ml identified patients at higher risk for post-operative DVT. Heparin reduced plasma TAT levels and FVII consumption following surgery, suggesting that heparin modulates coagulation associated with cancer surgery. The results of this study also suggest that the pre-operative [TAT] may identify patients with higher risk for post-operative DVT.

Adult↗
PubMed1993

Idarubicin in the initial treatment of adults with acute lymphoblastic leukemia: the effect of drug schedule on outcome.

Fifty two adults (aged 15 to 66 years) with newly diagnosed acute lymphoblastic leukemia (ALL, n = 47) or lymphoid blast phase chronic myelogenous leukemia (Ly-CML, n = 5) were managed with three distinct protocols containing idarubicin at a cumulative dose of 36, 20, and 10 mg/m2, respectively, plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). IVAP-1 was highly toxic and gave a low complete remission (CR) rate (7/17, 41%). Nine patients died of complications while severely neutropenic, and one had resistant disease. In contrast, 24 of 28 patients subsequently treated with IVAP-2 achieved a CR (86%, p 0.005), the rate of both hematological and extrahematological toxicity being significantly reduced compared with IVAP-1 (p < 0.05). With IVAP-3, 6/7 patients aged > 60 years achieved CR. IVAP-2 with total idarubicin 20 mg/m2 is a very effective and well tolerated regimen for the initial treatment of adults with ALL.

Adolescent↗
PubMed1993

Intensive therapy for adult acute lymphoblastic leukemia: preliminary results of the idarubicin/vincristine/L-asparaginase/prednisolone regimen.

Between June 1991 and September 1992, 80 patients with adult acute lymphoblastic leukemia (ALL) (newly diagnosed, n = 68; relapsed or refractory ALL, n = 7; lymphoid blast transformation of Philadelphia chromosome-positive chronic myelogenous leukemia [LT-CML], n = 5) were managed with a combination regimen consisting of idarubicin 36, 20, or 10 mg/m2 plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). Three patients with LT-CML and four with relapsing ALL had a complete remission. In the group of newly diagnosed patients aged 15 to 60 years treated with IVAP-1, the complete remission rate was only 44% due to the high incidence of toxic deaths. In contrast, 39 of 44 cases who subsequently received IVAP-2 achieved a complete remission (89%, P = .001), as did 62% of elderly patients who received IVAP-3. Hematologic and nonhematologic toxicity was significantly reduced with IVAP-2 compared with IVAP-1. The use of recombinant human granulocyte colony-stimulating factor in 24 patients was not associated with a reduced duration of granulocytopenia less than 0.5 x 10(9)/L, although there was a lower incidence of documented infections in patients receiving granulocyte colony-stimulating factor than in controls. Post-remission intensification with idarubicin-based courses, high-dose therapy with autologous bone marrow stem cell rescue, and rotational weekly therapy was feasible and its toxicity was manageable. These preliminary findings indicate that IVAP-2 (idarubicin 20 mg/m2) is a highly effective and well-tolerated regimen for remission induction of adult ALL.

Adolescent↗
PubMed1992

Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo.

Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.

Adult↗
PubMed1991

[Clinical course of refractory anemia. Study of a case series of 56 patients].

We analysed the course and clinical features of a series of refractory anaemias (RA, RAEB, RAEBt). We could not find evidence to support the hypothesis that these three MDS classes are inevitably subsequent events of a single disease. Therefore aggressive treatment of RA, aimed at avoiding its evolution to RAEB or RAEBt, does not seem justified.

Adult↗
PubMed1990

Cancer procoagulant in acute non lymphoid leukemia: relationship of enzyme detection to disease activity.

Blast cell extracts from patients with acute non lymphoid leukemia (ANLL) express cancer procoagulant (CP). This factor X (FX) activator is distinct from tissue factor (TF) in that it does not require factor VII (FVII) to trigger blood coagulation, it acts as a cysteine proteinase and is not present in normal mononuclear cells. To assess whether there is any relationship between the presence of CP and the status of the disease, ANLL patients have been studied at diagnosis, during remission, at relapse. The procoagulant activity in either the presence or absence of F VII and sensitivity to cysteine proteinase inhibitors were tested on cell extracts. Immunoreactivity was explored with an anti-CP polyclonal antibody. Data obtained in 91 newly-diagnosed ANLL patients (subtypes M1 to M5, FAB classification) confirmed the presence of CP in M1 to M4 groups (mean +/- SE FVII-independent activity: M1 = 2.1 +/- 0.7 unit/mg; M2 = 5.7 +/- 1.7 unit/mg; M3 = 31.5 +/- 8 unit/mg; M4 = 1.6 +/- 1.2 unit/mg); CP was absent in the M5 type. In eight patients analyzed in a subsequent phase of partial remission, specific activity had dropped from 26.9 +/- 7.8 to 10.5 +/- 4.0 unit/mg. Activity was virtually absent (0-0.05 unit/mg) in the bone marrow of 37 patients studied at complete remission. Bone marrow samples from six subjects tested at different intervals after complete remission were repeatedly negative for CP but became positive 2 to 5 months before relapse. Upon relapse, the FVII independent activity rose to 24.2 +/- 8.2 unit/mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Alpha-2 antiplasmin in acute nonlymphoblastic leukemia.

The levels of alpha-2-antiplasmin (alpha 2-AP), antithrombin III (At III) and plasminogen were studied in 21 patients with acute nonlymphoblastic leukemia (ANLL) before and after induction chemotherapy and during bone marrow cellularity recovery after the postchemotherapy aplastic phase. In the patients with M2, M3 or M4 leukemia who had clinical and laboratory evidence of DIC, the alpha 2-AP levels were very low in the initial phase of the disease but improved significantly during recovery of marrow cellularity. At III and plasminogen values were in the normal range at disease onset and showed no significant modification during the course of leukemia. Proteolytic cleavage of alpha 2-AP by granulocyte proteases, rather than hyperfibrinolysis, may be responsible for the low levels of the inhibitor in the proliferative phase of ANLL. This alpha 2-AP deficiency may well contribute to hemorrhagic diathesis in ANLL independently of the presence or absence of hyperfibrinolysis or DIC. Moreover, the lower alpha 2-AP levels observed during the proliferative phase of ANLL may relate to disease activity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Possible mechanisms of fibrin deposition in the hypereosinophilic syndrome.

Patients with the hypereosinophilic syndrome (HES) are at increased risk of thrombosis and have signs of fibrin deposition in the myocardial cavity; the pathogenesis of these complications is still unknown. We have studied a 51-year-old man affected by HES with heart, lung, skin, and gastrointestinal involvement. Routine laboratory parameters of the hemostatic system were normal with the exception of blood fibrinolytic activity. The latter was evaluated by both diluted blood clot lysis time and euglobulin lytic activity on fibrin plates before and after 10 min venous occlusion. The fibrinolytic activity measured on four occasions during a 3-month period, was impaired both in basal conditions and following venous occlusion. Platelet studies on two different occasions before and during therapy showed spontaneous platelet aggregation, lowered threshold concentrations of various aggregating agents, reduced platelet regeneration time and increased plasma beta-thromboglobulin concentration. The patient's polymorphonuclear cells (more than 75% eosinophils) were devoid of any procoagulant activity (PCA). Instead, patient's mononuclear cells studied before therapy generated significantly higher PCA on stimulation by endotoxin than cells from control subjects. The procoagulant response to endotoxin decreased markedly during therapy. The observed abnormalities could, at least partially, contribute to fibrin deposition in HES.

Blood Coagulation Factors↗
PubMed1989

[Pulmonary mycosis as a complication of acute leukemia in the adult. Diagnostic study].

Pulmonary fungal infections complicating hematological malignancies are difficult to diagnose antemortem because clinical findings are actually considered to be not specific. From December 1984 to June 1986 we documented the clinical findings in sixteen patients, 9 with ANLL, 6 with ALL and 1 with CML + BC; all patients were diagnosed as pulmonary fungal infection and treated for this complication. Pulmonary infiltrates occurred after severe aplasia (range 5-90 days) or during bone marrow relapse. We studied pulmonary signs and symptoms (pleuritic pain, cough, hemoptysis, shortness of breath, rales, rub, bronchial murmur) both at the beginning and during the management of this infectious complication and we related them to chest x-ray findings, the duration of granulocytopenia, and fever. Our purpose was to identify clinical characteristics for these episodes and establish roentgenological criteria for prognosis. These findings should improve the possibilities for an early diagnosis and prompt treatment.

Acute Disease↗