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Biomedical subjects

G Avvisati

Publications and source records attributed to G Avvisati.

At least 19 recordsLinked to original sources
PubMed2006

Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features.

Although the occurrence of thrombosis in acute promyelocytic leukemia (APL) has been reported during retinoic acid treatment, no studies carried out in large clinical cohorts have specifically addressed this issue. We analyzed 124 APL patients treated with the all-trans retinoic acid and idarubicin protocol and compared clinico-biologic characteristics of 11 patients who developed thrombosis with those of 113 patients who had no thrombosis. In seven patients, the events were recorded during induction, whereas in four patients deep vein thrombosis occurred in the post-induction phase. Comparison of clinico-biological characteristics of patients with and without thrombosis revealed in the former group higher median white blood cell (WBC) count (17 x 10(9)/l, range 1.2-56, P=0.002), prevalence of the bcr3 transcript type (72 vs 48%, P=0.01), of FLT3-ITD (64 vs 28%, P=0.02), CD2 (P=0.0001) and CD15 (P=0.01) expression. No correlation was found with sex, age, French-American-British subtype, all-trans-retinoic acid syndrome or with thrombophilic state that was investigated in 5/11 patients. Our findings suggest that, in APL patients consistent biologic features of leukemia cells may predict increased risk of developing thrombosis.

Adult↗
PubMed2003

Treatment of elderly patients (> or =60 years) with newly diagnosed acute promyelocytic leukemia. Results of the Italian multicenter group GIMEMA with ATRA and idarubicin (AIDA) protocols.

In all, 134 elderly patients (median age 66 years, range 60-75 years) with newly diagnosed acute promyelocytic leukemia (APL) were enrolled in two successive protocols of the Italian multicenter group GIMEMA. All patients received an identical induction with all-trans retinoic acid and idarubicin; 116 (86%) entered complete remission (CR), two (2%) were resistant and 16 (12%) died during induction. After CR, 106 patients received further therapy whereas 10 did not, because of refusal (n=5) or toxicity (n=5). Consolidation consisted of three chemotherapy courses in the AIDA protocol (AIDA, 67 patients) or, since 1997, of an amended protocol including only the first cycle (amended AIDA, aAIDA, 39 patients). In the AIDA group, 43 patients (64%) completed consolidation, while seven (11%) and 17 (25%) patients were withdrawn after first and second courses, respectively; nine patients (13%) died in CR and 12 (18%) relapsed. In the aAIDA group, all patients received the assigned treatment; two patients (5%) died in CR and six (15%) relapsed. In the AIDA and aAIDA series, the 3-year overall and discase-free survival rates were 81 and 83% (P=NS), 73 and 72% (P=NS), respectively. We highlight here the frequency and severity of complications linked to intensive chemotherapy in this clinical setting and suggest that, in APL of the elderly, less intensive postremission therapy allows significant reduction of severe treatment-related toxicity and may be equally effective.

Aged↗
PubMed2002

Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol.

Alterations in the FLT3 gene, including internal tandem duplications (ITDs) and D835 mutations occur frequently in acute myelogenous leukemia. We investigated the prevalence and clinico-biological correlations of FLT3 ITDs and D835 mutations in 90 patients with acute promyelocytic leukemia (APL) receiving the AIDA protocol. Twenty patients in which both presentation and relapse material was available were analyzed sequentially. Thirty-three patients (37%) harbored the ITD, and seven (7.7%) the D835 mutation in blasts obtained at diagnosis. Presence of ITDs was strongly associated with high WBC count (P = 0.0001), M3 variant (P = 0.0004), and the short (BCR3) PML/RARalpha isoform (P = 0.003). There was no difference in response to induction in the two ITD+ve and ITD-ve groups, while a trend towards inferior outcome was observed for ITD+ve cases when analyzing disease-free survival (DFS) and relapse risk (RR). These differences, however, did not reach statistical significance. Sequential studies showed variable patterns in diagnostic and relapse material, ie ITD (-ve/-ve, +ve/+ve, +ve/-ve, -ve/+ve) and D835 (-ve/-ve, +ve/-ve, -ve/+ve). Our results indicate that FLT3 alterations are associated in APL with more aggressive clinical features and suggest that these lesions may not play a major role in leukemia progression.

Acute Disease↗
PubMed2002

Melphalan treatment in patients with myelofibrosis with myeloid metaplasia.

Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement >5 cm and/or transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count >20 x 10(9)/l and/or platelets >1.0 x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66.7%) achieved a response after a median time of 6.7 months: 26 (26.3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40.4%) showed an improvement >50% (partial response, PR). Thirty-three patients (33.3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28.4 and 26 months respectively: median survival of CR + PR patients was 71.2 months (95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the non-responders (log-rank test, P =0.002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR = 2.4) and not achieving any type of response, either partial or complete (HR = 3.9). In conclusion, Melphalan could be a promising first-line option for MMM patients with clinical or haematological symptoms requiring treatment.

Adult↗
PubMed2001

Extramedullary involvement at relapse in acute promyelocytic leukemia patients treated or not with all-trans retinoic acid: a report by the Gruppo Italiano Malattie Ematologiche dell'Adulto.

PURPOSE: Recent reports of extramedullary disease (EMD) at recurrence in acute promyelocytic leukemia (APL) have raised increasing concern about a possible role of retinoic acid (RA) therapy. PATIENTS AND METHODS: We analyzed the risk of developing EMD localization at relapse in APL patients enrolled onto two consecutive studies of the Gruppo Italiano Malattie Ematologiche dell'Adulto. The studies investigated chemotherapy alone (LAP0389) versus RA plus chemotherapy (AIDA). RESULTS: When all relapse types were taken into account, 94 (51%) of 184 patients and 131 (18%) of 740 patients who attained hematologic remission underwent relapse in the LAP0389 and AIDA studies, respectively (P < .0001). EMD localization was documented in five (5%) of 94 and 16 (12%) of 131 patients (P = .08). Hematologic and/or molecular relapse was diagnosed concomitantly in all but two patients with EMD in the AIDA study. For patients in the LAP0389 and AIDA series, the probability of EMD localization of any type at relapse was 3% and 4.5%, respectively (P = .79), while the probability of CNS involvement was 0.6% and 2% (P = .28). No significant differences were found with regard to mean WBC count and promyelocytic leukemia/retinoic acid receptor-alpha junction type in comparisons of patients with EMD and hematologic relapse. CONCLUSION: APL patients receiving all-trans retinoic acid in addition to chemotherapy have no increased risk of developing EMD at relapse as compared with those treated with chemotherapy alone.

Adult↗
PubMed2001

As compared to kaolin clotting time, silica clotting time is a specific and sensitive automated method for detecting lupus anticoagulant.

Lupus anticoagulants (LAs) are antiphospholipid antibodies capable of interfering with the coagulation system and modifying in vitro the phospholipid-dependent clotting tests. Colloidal silica was used as activator to perform an activated partial thromboplastin time (aPTT) in 73 plasma samples with pathologically elevated kaolin clotting time (KCT) values using a photooptical automated coagulometer. Samples were incubated for 5 min with micronized silica, and after recalcification, the clotting times were measured. Pathologically prolonged results were confirmed by a confirmation and a neutralization test adding platelet-poor normal plasma (PPNP) and natural phospholipids, respectively. Silica clotting time (SCT) was abnormally elevated in 72/73 (98.6%) (mean ratio 1.71 +/- 0.28) KCT positive samples and normalized (mean ratio 1.03 +/- 0.16) after adding natural phospholipids to test plasma. The values expressed as SCT and KCT ratios were significantly correlated (r = .92; P < .001). SCT was normal in 40 healthy subjects utilised as controls (mean ratio 0.99 +/- 12). Sensitivity, specificity and diagnostic accuracy of SCT were 98.6%, 100% and 97.6%, respectively. Our data suggest that SCT is a sensitive test for detecting LA with a prolonged KCT in automated photooptical coagulometers. This peculiarity makes it particularly useful, in combination with diluted Russel viper venom time (dRVVT), for large-scale screening tests on LA.

Adult↗
PubMed2001

Clinical and biological features of acute myeloid leukaemia occurring as second malignancy: GIMEMA archive of adult acute leukaemia.

Between July 1992 and June 1996, 3934 new cases of acute leukaemia were registered in the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Archive of Adult Acute Leukaemia. Two hundred cases (5.1%) presented with a history of primary malignancy (PM), 179 of which were acute myeloid leukaemia (AML). The median age of these cases was significantly higher than that of other primitive AML (63 years vs. 57 years; P < 0.001). The number of men was significantly lower than the number of women [74/1544 (4.8%) vs. 105/1420 (7.4%); odds ratio (OR) 0.63, 95% confidence interval (CI) 0.46-0.87; P < 0.002], as was the number of patients aged <65 years [104/1963 (5.3%) vs. 75/1001 (7.5%); OR 0.69, 95% CI 0.50-0.95; P < 0.01]. An increased incidence of cancer was observed among first-degree relatives of patients with AML occurring after a PM (secondary AML; sAML) [66/179 (36.9%) sAML vs. 757/2785 (27.2%) de novo AML, age adjusted; OR 2.62, 95% CI 1.07-6.42; P < 0.005]. Prevalent types of PM were breast cancer, lymphoma and Hodgkin's disease. sAML occurred after a median latency of 52 months (range 2-379). Of the 122 patients who received chemotherapy for sAML, 67 patients (55%) achieved a complete remission (CR), three a partial remission, 15 (12%) died in induction and 37 (30%) were unresponsive. The median duration of CR was 30 weeks (range 4-250). The median overall survival was 7 months (range 1-196). Comparing acute promyelocytic leukaemia with all other French-American-British (FAB) groups, a significant increase in CR achievement was observed [14/18 (77.7%) vs. 53/101 (52.4%), P < 0.046] as well as in median CR duration (55 vs. 24 months, P < 0.02). The analysis of our data suggests that not only previous chemotherapy but also genetic predisposition could play a role in the pathogenesis of sAML.

Acute Disease↗
PubMed2001

ProC global: a new automated screening assay for the evaluation of total function of the protein C system.

Protein C (PC) pathway represents a major physiologic inhibitory mechanism regulating the coagulation cascade. A new automated functional screening assay (ProC Global) for the evaluation of the PC-system was tested to define its ability to identify patients with known inherited defects such as factor V (FV) Leiden mutation and PC and protein S (PS) deficiency. A total of 249 patients who were symptomatic or asymptomatic for previous venous thromboembolism (VTE) were evaluated, 50 of whom had FV Leiden mutation, 36 had PC deficiency, and 34 had PS deficiency. One hundred healthy subjects were also tested, as well as 40 blood donors of both sexes in whom coagulation abnormalities were not found. Results of ProC Global test were expressed as normalized ratio (NR) and values below an established cut-off level were consistent with a positive test. ProC Global was positive in all 50 patients with the FV Leiden mutation (mean NR = 0.59; range, 0.37 to 0.69). ProC Global correctly identified 32 of 36 (89%) PC defects (mean NR = 0.63; range, 0.34 to 1.21) and 25 of 34 (73.5%) PS defects (mean NR = 0.76; range, 0.5 to 1.23). Overall, 92.5% of hereditary defects of the PC system considered in this study were identified by ProC Global test. ProC Global exhibited NR above cut-off level in all 40 blood donors without coagulation defects. ProC Global is a new automated screening test with some diagnostic potential in identifying patients with defects of the PC system. However, ProC Global in its current form cannot substitute the assay of each single component of this inhibitory system in the daily screening for thrombophilia.

Adolescent↗
PubMed2001

Prevention of delayed emesis induced by moderately emetogenic chemotherapy in patients with acute emesis: a pilot study with ACTH-Depot plus tropisetron.

The rates of delayed nausea and vomiting by moderately emetogenic chemotherapy in patients with previous experience of acute emesis are usually quite high. This is a pilot study aiming to evaluate the safety of a new antiemetic schedule to prevent delayed emesis in this subset of patients. During 5 consecutive cycles of moderately emetogenic chemotherapy, we evaluated 50 patients (15 males) who experienced acute emesis in the first cycle of treatment. The regimen for prevention of delayed emesis consisted of daily tropisetron (5 mg orally from d 2 to d 6 of each chemotherapeutic cycle) associated to ACTH-Depot (1 mg intramuscularly 24 and 68 h after the initiation of chemotherapy). In 77% of chemotherapy cycles, there was a total elimination of nausea and vomiting, whereas in the remaining 23% of cycles, there was a major response defined as < or = 2 vomiting episodes per cycle or nausea grade 1 according to the WHO. The efficacy of the antiemetic regimen persisted during the entire treatment program without the appearance of toxic effects. The proposed antiemetic regimen is highly active in preventing delayed nausea and vomiting episodes in patients receiving moderately emetogenic chemotherapy. Moreover, no toxic effects were observed. These promising results require confirmation by a randomized trial.

Administration, Oral↗
PubMed2001

Unusual presentation of Hodgkin's disease mimicking inflammatory bowel disease.

A case of a 32-years old man with a long lasting history of inflammatory bowel disease (IBD) is described. He was treated in the past with adequate medical therapy with considerable improvement of the symptoms. However, after the resolution of the last episode of abdominal pain and diarrhoea, because of multiple protruding masses and sub-stenotic regions found during a colonoscopy, the patient underwent a right enlarged hemicolectomy with jejunal resection. During the surgical procedure 16 enlarged lymphnodes were removed. The histological examination of the surgical specimen showed the presence of numerous Reed-Sternberg cells, compatible with a diagnosis of Hodgkin's disease (HD). None of the removed lymphnodes showed the presence of tumor cells, and in addition the systemic staging procedure was negative. After staging, the ABVD regimen was started, achieving a complete clinical and pathological response. This is a rare case of primary extranodal HD localized to the colon, in a patient with a long standing history of IBD, who showed an optimal response to chemotherapy. The case and the differential diagnosis with other pathological entities of the bowel is discussed.

Adult↗
PubMed2001

Acute promyelocytic leukemia: clinical and morphologic features and prognostic factors.

The most impressive clinical feature of acute promyelocytic leukemia (APL) at diagnosis is the presence in 80% to 90% of patients of a severe hemorrhagic syndrome. Recent data favor a fibrinolytic/proteolytic process rather than a disseminated intravascular coagulation as the mechanism mainly responsible for the hemorrhagic diathesis in APL. Morphologically, two main cytologic variants have been Identified: the classical hypergranular APL (M3), which represents the great majority of all APL, and the microgranular variant (M3v), which accounts for about 15% to 20% of all APL. A rare basophilic variant has also been described. With regard to prognosis, it has markedly changed from that of a rapidly fatal acute leukemia to that of a highly curable disease. This revolutionary progress was mainly due to the introduction during the 1990s of all-trans retinoic acid (ATRA) for the treatment of this disease. After the introduction of ATRA, in addition to clinical features such as hyperleukocytosis (white blood cell count > 10 x 10(9)/L) or thrombocytopenia (platelet count < 10 x 10(3)/L) at presentation, immunophenotype markers and polymerase chain reaction status for promyelocytic leukemia/retinoic acid receptor-alpha during follow-up also had an impact on prognosis.

Antineoplastic Agents↗
PubMed2001

High dose of idarubicin-based regimen for diffuse large cell AIDS-related non-Hodgkin's lymphoma patients: a pilot study.

BACKGROUND AND OBJECTIVES: Intensive chemotherapy (CHT) in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL patients) is a vexing problem. Our purpose was to evaluate the feasibility of a high dose idarubicin (HD-IDA)-based regimen in diffuse large cell (DLC) AIDS-NHL patients. DESIGN AND METHODS: Fourteen stage I-IV untreated DLC AIDS-NHL patients with a performance status <3 and no prior AIDS-related diseases received CIOD: cyclophosphamide, HD-IDA (25 mg/m2 in 8 patients, 20 mg/m2 in 6 patients) vincristine and dexamethasone plus granulocyte colony-stimulating factor (G-CSF) and prophylaxis against infections. The outcomes measured were: rate of response, disease-free survival (DFS), overall survival (OS) and the impact of chemotherapy on immunologic and virological parameters. RESULTS: Complete response was achieved in 13/14 cases (response rate: 93%). The median time of response and survival was 33 (range 5-79) and 35.5 (range 6-84) months, respectively. At 60 months the DFS and OS were 71% and 44%, respectively. CIOD with idarubicin 20 mg/m2 was better tolerated than that with 25 mg/m2 and was administered with a higher mean average-relative-dose-intensity (95.38+/-7% vs 83.35+/-15.59%, p=0.0001). Opportunistic infections were more frequent in patients with a baseline CD4 <100 than those with >100 cells/microL (4/5 vs 1/9: p=0.0229). After 3 CIOD courses the mean CD4 cells/microL was significantly lower (p=0.001) and the mean HIV.1 RNA load was significantly higher (p=0.045) than at baseline. INTERPRETATION AND CONCLUSIONS: The proposed chemotherapeutic regimen for AIDS-related non-Hodgkin's lymphoma is feasible in an outpatient setting in selected patients with relatively well-preserved immune function.

Adult↗
PubMed2000

Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups.

Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RAR alpha-positive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 +/- 2% and 86 +/- 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count </= 10 x 10(9)/L, platelet count > 40 x 10(9)/L), intermediate-risk (WBC count </= 10 x 10(9)/L, platelets </= 40 x 10(9)/L), and high-risk (WBC count > 10 x 10(9)/L) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (Blood. 2000;96:1247-1253)

Adolescent↗
PubMed2000

Molecular and cytogenetic remission in a case of subtype M4E acute myelogenous leukemia with minimal monochemotherapy: high sensitivity or spontaneous remission?

Complete remission was observed in an adult patient with acute myelogenous leukemia after minimal monochemotherapy. Remission occurred after a severe febrile pneumonia and was accompanied by cytogenetic and molecular remission. The hypothesis of spontaneous remission was raised, even if a high sensitivity to low-dose cytostatics cannot be excluded. Such spontaneous complete remissions, often associated with bacterial infections and blood transfusions, are extremely rare, and are usually of short duration. Previous cases are summarized, and the role of etiologic factors is discussed.

Adult↗
PubMed2000

High levels of antiphospholipid antibodies are associated with cytomegalovirus infection in unrelated bone marrow and cord blood allogeneic stem cell transplantation.

Antiphospholipid antibodies (APA) are a family of autoimmune and alloimmune immunoglobulins recognizing protein-phospholipid complexes in in vitro laboratory test systems. These antibodies have been associated with several conditions (malignancies, autoimmune diseases, infections, use of drugs); moreover, a syndrome capable of inducing thromboembolic disease has recently been associated with the presence of these antibodies. The aim of this prospective study was to investigate the levels of APA in subjects affected by haematological malignancies undergoing allogeneic haematopoietic stem cell transplantation (ASCT). Between March 1996 and December 1997, 32 patients undergoing ASCT were studied prospectively until day +180 from transplant. The mean values of IgG and IgM anticardiolipin antibodies (ACA) increased in recipients of stem cells from anunrelated donor, and a statistically significant difference inACA IgG mean value between unrelated and related transplanted patients was demonstrated between days +95 and +180. All of the subjects who received stem cells from an unrelated donor had APA levels higher than the mean normal value +3 SD vs. 35% of those receiving stem cells from a related donor (P < 0.01). The reason for such a difference may be a result of the different incidence in documented cytomegalovirus (CMV) infection in the two groups (83% vs. 23%; P < 0.01), as indicated by the significant correlation between APA positivity and CMV infection (P < 0.05). No relationship was found between APA, conditioning regimen and acute or chronic graft vs. host disease (GVHD). Moreover, we did not observe any thromboembolic disorder or veno occlusive disease (VOD).

Adolescent↗