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Biomedical subjects

M Federico

Publications and source records attributed to M Federico.

At least 73 records · Page 4Linked to original sources
PubMed1996

Twelve years experience with high-dose therapy and autologous stem cell transplantation for high-risk Hodgkin's disease patients in first remission after MOPP/ABVD chemotherapy.

High-dose therapy followed by autografting can cure patients with aggressive Hodgkin's disease (HD) refractory or with early relapse to first-line combination chemotherapy. On the other hand, the eradication of the disease is rarely achieved in heavily pretreated patients. It has been suggested that patients with HD with very high risk characteristics at diagnosis, often relapse despite appropriate therapy with 7-8 drugs combination. Thus it seems to us that such patients are potential candidates for early autografting during first remission. Twelve years ago, we initiated a pilot study to investigate whether patients with very high risk characteristics, would benefit from early autografting. The application of early autografting was compared with our historical group of patients in complete remission after receiving MOPP/ABVD, who had the same negative prognostic characteristics, refused autografting and who did not receive other treatment after achieving complete remission. Among the 22 consecutive patients entered into the pilot study and autografted, 18 are alive and 17 (77%) remain alive in unmaintained remission at a median of 86 months. One patient (4%) died of interstitial pneumonitis in the transplantation group. Only 8/24 (33%) patients, who did not receive an autograft, are currently alive and disease free at a median of 89 months. In conclusion, the early application of autografting appears to improve the outcome in patients with very high risk HD who achieved remission with MOPP/ABVD.

Adolescent↗
PubMed1996

High-dose therapy autologous stem cell transplantation vs conventional therapy for patients with advanced Hodgkin's disease responding to first-line therapy: analysis of clinical characteristics of 51 patients enrolled in the HD01 protocol. EBMT/ANZLG/Intergroup HD01 Trial.

Whether high-dose therapy (HDT) plus autologous stem cell transplantation (ASCT) ought to be included in the initial treatment plan for those patients with unfavourable Hodgkin's disease, a wide cooperative study (HD01 protocol) was approved, comparing HDT followed by ASCT vs conventional chemotherapy (CT). Patients were eligible for the study if they had at least two of the following adverse prognostic factors: high serum LDH levels, mediastinal mass >0.45, more than one extranodal involved site, low hematocrit (<34% for women and <38% for men), and inguinal involvement. Those patients achieving complete or partial remission with four courses of ABVD or ABVD-containing chemotherapy were randomized to receive either HDT plus ASCT or four additional courses of chemotherapy, followed by ASCT in second remission, if appropriate. Between April 1993 and September 1995, 55 patients from 14 different centers have been enrolled into the trial. Twenty patients (45%) were in stage IV, and 37 patients (84%) had systemic symptoms. Twenty-seven patients (61%) had two adverse prognostic factors, and 17 patients (39%) had three or more risk factors. After four cycles of ABVD-containing CT, 44 patients were assessable for response. Overall 12 patients achieved CR (27%), 25 obtained a PR (57%) and seven patients failed to respond (16%). Thirty-six patients were randomized between ASCT (20 patients) or four additional cycles of conventional CT (16 patients). With a median follow-up after ASCT of 13 months (range 1-23 months), no major ASCT-related toxicity has been reported to the trial office. In conclusion, the first 44 patients registered in the HD01 trial and assessable for response, had a very aggressive disease and responded poorly to conventional CT, thus warranting a more aggressive approach, such as HDT followed by ASCT.

Adolescent↗
PubMed1995

In vitro human immunodeficiency virus-1 infection of purified hematopoietic progenitors in single-cell culture.

Uni- or multi-lineage suppression of hematopoiesis is observed in the majority of acquired immunodeficiency syndrome (AIDS) patients. The mechanism(s) underlying these abnormalities is not understood: particularly, the human immunodeficiency virus (HIV) infection of hematopoietic progenitor and stem cells (HPCs/HSCs) is highly controversial. We report that CD34+ HPCs from adult peripheral blood (PB) are in part CD4+ and susceptible to in vitro HIV infection. Primitive CD34+ HPCs were approximately 80% purified from PB. Double labeling for CD34 and CD4 membrane antigens was shown for 5% to 20% of the purified cells, thus suggesting their potential susceptibility to HIV-1 infection. The enriched HPC population, challenged with purified or unpurified HIV-1 strains, was cloned in unicellular methylcellulose culture. The single colonies generated by erythroid burst-forming units (BFU-E), granulocyte-macrophage colony-forming units (CFU-GM), and granulocyte-erythroid-macrophage-megakaryocyte colony-forming units (CFU-GEMM) were analyzed for the presence of HIV, ie, for gag DNA, tat mRNA, and p24 protein by PCR, reverse transcription PCR (RT-PCR), and enzyme-linked immunosorbent assay, respectively. In the first series of experiments incubation of HPCs with HIV-1 at multiplicities of infection (MOI) ranging from 0.01 to 10 TCID50/cell consistently yielded an 11% to 17% infection efficiency of BFU-E-generated colonies, thus indicating the sensitivity of HPCs to in vitro HIV infection. An extensive series of experiments was then performed on HPCs challenged with HIV at 0.1 MOI level. In the initial studies proviral gag sequences were detected in 9.2% of 121 analyzed CFU-GM colonies. In further experiments tat mRNA was monitored in 17% and 23% of BFU-E and CFU-GM colonies, respectively, but never in CFU-GEMM clones. Finally, 12% of CFU-GM clones and rare erythroid bursts were shown to be positive for the p24 viral protein. In control studies, purified HPCs grown in liquid suspension culture were induced to terminal unilineage erythroid, monocytic, or granulocytic differentiation: monocytes were consistently HIV-infected, whereas mature-terminal erythroblasts and granulocytes were not. Our observations indicate that a minority of primitive HPCs, but not of the multipotent type, is susceptible to in vitro HIV infection. These observations may reflect on the in vivo hematopoietic impairment in AIDS patients; more important, they provide an experimental model for studies on HIV hematopoietic infection and in vitro tests for anti-HIV HSC gene therapy.

Adult↗
PubMed1995

Full expression of transfected nonproducer interfering HIV-1 proviral DNA abrogates susceptibility of human He-La CD4+ cells to HIV.

An Hut-78 cell clone (F12) harboring a nonproducer human immunodeficiency virus-1 (HIV) variant, and showing a complete resistance to HIV-1 or HIV-2 superinfection, was previously characterized. We demonstrated that the replication of the superinfecting HIVs is blocked at the retrotranscription step, despite the CD4 down-regulation, since HIVs are able to cross the Hut-78/F12 cell membrane. In order to establish if the expression of the HIV-1 variant (F12/HIV) could be per se sufficient to induce the homologous viral interference shown in the F12 cells, the whole F12/HIV provirus was cloned and transfected in He-La CD4+ cells. In F12/HIV expressing He-La CD4+ clones, both the viral proteins expressed and the HIV nonproducer phenotype remain unmodified compared to F12 cells. Furthermore, despite the full expression of CD4 HIV receptors, the life cycle of the superinfecting HIV could be either strongly inhibited or totally abolished, depending on the cell clone considered. The inhibition of the superinfecting HIV was also reproduced when an HIV infectious molecular clone was transfected in F12/HIV He-La CD4+ clones, thus indicating that a post-cDNA synthesis block may operate against the superinfecting HIV. These data demonstrate that HIV susceptibility could be abrogated in cells expressing the F12/HIV genome, even in absence of any CD4 down-regulation.

CD4 Antigens↗
PubMed1995

Anaplastic large cell lymphoma (CD30+/Ki-1+). Analysis of 35 cases followed at GISL centres.

Between January 1988 and June 1992, 35 patients with primary anaplastic large cell lymphoma (ALCL)CD30+ were referred to one of the institutions participating in GISL (Gruppo Italiano per lo Studio dei Linformi). 16 patients were treated with ProMACE-CytaBOM, two with MACOP-B, one with CHOP and one with LSA2-L2. As of November 1990, all newly diagnosed patients were treated with MOPP/EBV/CAD hybrid. 27 (77%) cases of ALCL CD30+ and 8 (23%) cases of Hodgkin's-related (HR) lymphoma CD30+ were diagnosed. Extranodal disease was present in 22 cases (63%), and 8 patients (23%) had primary bone marrow involvement. Twenty-three complete remissions (CR) (66%), six partial remissions (PR) (17%) and six no remissions (NR) (17%) were achieved with induction therapy. Results achieved with ProMACE-CytaBOM and MOPP/EBV/CAD hybrid were comparable. The overall response rate (CR+PR) was 85% for patients with classic ALCL CD30+ and 87% for those with HR lymphoma CD30+. The 3 year estimated overall survival rate was 66% and the 3 year relapse free survival rate was 65% for the entire group. The only significant favourable prognostic factor was the achievement of CR with initial therapy. Our findings suggest that ALCL (CD30+/Ki-1+) has a clinical outcome similar to aggressive non-Hodgkin's lymphoma (NHL). The use of an anthracycline-containing regimen will provide a change of cure in approximately 65% of cases.

Adolescent↗
PubMed1995

Effects of thymostimulin with combination chemotherapy in patients with aggressive non-Hodgkin's lymphoma. A report from the Italian Lymphoma Study Group (GISL).

The purpose of this study was to test the efficacy and safety of thymostimulin (TS) administered in addition to conventional chemotherapy in patients with intermediate- and high-grade non-Hodgkin's lymphoma (IG, HG-NHL). A total of 150 patients with newly diagnosed IG- or HG-NHL were entered in a multicenter trial to compare the effectiveness of two different third-generation regimens (MACOP-B versus ProMACE-CytaBOM) and were randomized to receive chemotherapy (CT) alone or CT + TS. In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin. TS was administered i.m. at a dose of 1 mg/kg daily on days 22-28 of each drug course to patients treated with ProMACE-CytaBOM, and on days 22-29, 50-57, and 77-85 to patients treated with MACOP-B. There were 134 fully evaluable patients: 68 treated with CT alone and 66 treated with CT + TS. Patients treated with CT + TS had a higher complete remission (CR) rate compared to patients given CT alone (59.1% vs 42.4%; P = .05). CR were significantly higher for patients treated with CT + TS in the groups with IG-NHL (P = .01), in those aged less than 60 years (P = .05), with good performance status (P = .05), and normal hemoglobin levels (P = .05). Four-year survival rates are 64.5% for patients treated with CT + TS and 43.0% for those treated with CT alone (P = .30). No difference between the two treatment arms have been observed as regards drug-related toxicity and the number and severity of infectious episodes. The use of TS during the 7 days before chemotherapy has been associated with a significantly superior CR rate. The advantage of CT + TS was mostly obtained in patients with IG-NHL, and those with good performance status or normal hemoglobin levels. In these patients TS may have potentiated the host reactions against the tumor, leading to an increase in NK activity and the production of cytokines. This postulated increase in the effectiveness of chemotherapy after TS might also explain the absence of the expected myeloprotective action.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

A nonproducer, interfering human immunodeficiency virus (HIV) type 1 provirus can be transduced through a murine leukemia virus-based retroviral vector: recovery of an anti-HIV mouse/human pseudotype retrovirus.

The expression of a human immunodeficiency virus (HIV) type 1 provirus (F12-HIV) cloned from a nonproducer, chronically infected CD4 down-regulated Hut-78 cell clone (F12) does not lead to the formation of viral particles and, upon transfection in HeLa CD4+ cells, confers resistance to HIV superinfection without affecting the CD4 receptor exposure. In an attempt to transfer the anti-HIV properties of F12-HIV into human primary cell, we constructed a Moloney murine leukemia virus-based retroviral vector containing an F12-HIV genome lacking the 3' long terminal repeat and part of the nef gene, which was expressed under the control of its 5' long terminal repeat. The F12-HIV genome was inserted in the orientation opposite to that of the murine leukemia virus transcriptional unit and was designated the N2/F12-HIV nef-antisense vector. Lymphoblastoid CEMss cells, as well as human peripheral blood lymphocytes, were successfully transduced by the recombinant retrovirus emerging from the producer PA317 clones. CEMss clones expressing the F12-HIV nef-antisense vector became resistant to HIV superinfection even at the highest utilized multiplicity of infection (10(5) 50% tissue culture infective doses per 10(6) cells). In transduced CEMss cells the viral interference induced by the F12-HIV expression is not due to CD4 HIV receptor down-regulation. Nonproducer, interfering HIV proviruses transduced into retroviral vectors may, therefore, provide an alternative strategy for the protection of CD4+ human primary cells from HIV infection, which strategy may be used in designating a safe and efficient gene therapy protocol for patients with AIDS.

3T3 Cells↗
PubMed1995

Drug injection in jugular veins: a new risk factor for vascular diseases in HIV-infected patients? A case report.

The authors describe a rare case of diffused thrombosis of the superficial veins in the whole body and periphlebitis with perivascular abscesses in an human immunodeficiency virus (HIV)-infected drug abuser who was using neck veins to inject cocaine and heroin. In addition the patient presented oral candidiasis, hepatitis C virus infection, bronchopneumonitis, and endocarditis of the tricuspid valve with valvular failure. The conditions of the patient needed repeated vascular catheterizations for therapy administration. Similar pathologies, in HIV-infected patients, highly increase the risk of opportunistic infections, especially in the encephalic territory; in addition the need for vascular catheterizations represents a further risk factor for bacterial infections.

Abscess↗
PubMed1995

ProMECE-CytaBOM vs MACOP-B in advanced aggressive non-Hodgkin's lymphoma: long term results of a multicenter study of the Italian Lymphoma Study Group (GISL).

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m2 of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure. Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

In vitro drug testing of ovarian cancer using the human tumor colony-forming assay: comparison of in vitro response and clinical outcome.

The purpose of this study was to assess the prognostic value of in vitro drug chemosensitivity testing using the Hamburger-Salmon human tumor colony-forming assay (HTCA) in fresh tumor samples obtained from newly diagnosed patients with stage II-IV ovarian cancer undergoing maximum cytoreductive surgery and prior to platinum-based chemotherapy. The HTCA was performed on fresh ovarian cancers obtained from 93 patients at their initial exploratory laparotomy to evaluate in vitro sensitivity to cisplatin, carboplatin, and cyclophosphamide following a 1-hr drug exposure. Prospective clinical follow-up was performed on all patients with the primary study endpoints being pathologically proven complete response at second-look surgery and disease-free and overall survival durations. In vitro drug sensitivity was strongly dose-dependent. At a concentration of 5 micrograms/ml only 23% of tumor samples were sensitive (as defined by a > or = 50% decrease in tumor colony-forming units compared to controls) to cisplatin; 13% of tumors were sensitive to carboplatin at a concentration of 50 micrograms/ml and 11% to 4-OH-cyclophosphamide at a concentration of 1 microgram/ml. At doses which were 10 times the previously stated concentrations, the sensitivity rates to cisplatin, carboplatin, and 4-OH-cyclophosphamide increased to 72, 63, and 53%, respectively. Subjects were categorized as having drug-sensitive disease if HTCA results showed in vitro drug sensitivity to at least one of the agents used in their primary chemotherapy. Multivariate analysis failed to show any advantage in clinical response rate, progression-free interval, or survival duration for patients with drug-sensitive disease compared to drug-resistant disease; however, there was evidence of a trend toward an enhanced pathologically proven complete response rate in patients who had chemosensitive tumors in vitro. Second-look surgery was performed in 28 of 55 patients with optimal surgical resections and no clinical evidence of disease at the completion of their primary chemotherapy. Fifty percent (5/10) of patients with drug-sensitive disease achieved a pathologic complete response, while only 3/18 (17%) patients with drug-resistant tumors had a documented pathologic complete response (P = 0.13). As reported in other ovarian cancer studies, patient characteristics which were found to be significantly associated with survival were stage of disease (II-III vs IV), optimal primary surgical resection (i.e., < 1 cm2 residual tumor) vs suboptimal resection, clinical measurability of disease at initiation of chemotherapy, and response to primary chemotherapy. In conclusion, in vitro drug sensitivity, as measured by the HTCA, does not appear to be an independent prognostic factor for survival in patients with stage II-IV epithelial ovarian cancer who undergo standard treatment with tumor debulking surgery and primary platinum-based chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL.

PURPOSE: In 1987 the Italian Cooperative Group for the Study of hairy cell leukemia (HCL) started a prospective trial with the following three major aims: 1) to confirm the effectiveness of alpha-IFN as first-line treatment; 2) to assess the usefulness of splenectomy as consolidation treatment in patients achieving a satisfactory partial remission (PR) with alpha-IFN, and 3) to explore whether splenectomy in patients achieving complete remission (CR) with alpha-IFN can reduce the risk of relapse after discontinuation of the drug. PATIENTS AND METHODS: One-hundred seventy-seven patients with histologically-confirmed HCL were registered in the HCL88-A trial between December 1987 and January 1992. Inclusion criteria included no previous treatment and age less than 66 years. All patients received total doses of 3 MU of alpha-IFN daily for 12 months except for those who achieved early CR and would stop treatment after 6 or 9 months. Patients could be treated with different alpha-IFNs. At the time of the present analysis, 166 patients (93.8%) were fully evaluable. RESULTS: Treatment of HCL patients with alpha-IFN at the onset of the disease resulted in 28 CR (16.9%), 103 PR (62.0%), and 27 Minor Remissions (MR) (16.3%). Patients treated with different alpha-IFNs achieved similar results: the overall response rate (CR + PR + MR) was 92.7%, 97.2%, and 95.3% for patients treated with r-alpha-2a, r-alpha 2b, and alpha-N1, respectively. The presence of a leukemic phase and a poor performance status were associated with a statistically significant lower response rate. Patients who were randomly assigned and underwent splenectomy after achieving a PR had a better but not significant 4-year progression-free survival than cases randomized for observation (53% vs. 22%, p = 0.116). Overall, 5 patients died after study entry, with an actuarial 5-year survival rate of 96% for the entire group of 166 patients. After a mean follow-up time of 38 months, only one second malignancy has been recorded. CONCLUSIONS: Initial therapy with alpha-IFN, regardless of the type of alpha-IFN used, induces satisfactory responses in the majority of patients with HCL, but in most instances discontinuation of treatment results in recurrence of disease. In most cases alpha-IFN improves the performance status of patients and favors a satisfactory bone marrow recovery and thus could still play a role in the initial management of the disease. Although splenectomy following alpha-IFN could prolong the progression free survival, its use should be restricted to selected cases.

Adult↗
PubMed1994

Long term results of interferon treatment in hairy cell leukemia. Italian Cooperative Group of Hairy Cell Leukemia (ICGHCL).

Eighty nine of 104 patients with hairy cell leukemia (HCL), enrolled between 1985 and 1987 in a multicenter prospective study on human lymphoblastoid IFN alpha-n1, were evaluable for long-term follow-up. The induction treatment, 3 MU/mq daily for a median of 5.7 months, produced a response of 93%, complete+partial response (CR+PR) = 80%, minor (MR) = 13%. Neither prior splenectomy nor pre-treatment variables were associated with the rate of response to IFN. However maintenance treatment of 3 MU/mq weekly given randomly had a slightly significant effect on failure free survival (FFS). Of the 43 patients who relapsed, 31/36 (86%) obtained a new response with IFN. No differences in FFS were recorded between first and second response. At the third induction 7/11 patients were treated again with IFN, 4/7 obtaining some response, but the FFS was significantly worse. The overall survival is still 85%. We conclude that (1) IFN should be used as chronic uninterrupted treatment for HCL, (2) reduced dosage is sufficient to prolong the disease free status and (3) continuous lymphoblastoid IFN administration seems not to be associated with the development of resistance to retreatment.

Aged↗
PubMed1994

Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Registry for hairy cell leukemia (HCL) has recorded 725 patients with HCL diagnosed over 25 years. We analysed this large series of patients with the aim of providing an evaluation of changes in clinical presentation, impact of initial therapy and modifications in prognostic factors over the period of two decades. Over time, a progressive down-staging of the disease at the onset, along with a reduction of patients with severe anemia and marked splenomegaly, has been observed. A second malignancy was found in 3.7% of patients, mostly detected several years after the onset of HCL. A striking improvement of survival rates has been observed, from 58.9% survival at five years for patients diagnosed before 1985 to 87.5% at five years for patients diagnosed after 1985 (p < 0.0001). Before 1985 hemoglobin alone provided prognostic information, whereas after 1985, clinical stage and the number of leukocytes correlated better with patient outcome. Survivals at 5 and 10 years were 34.4% and 29.6% respectively for untreated patients, 58.8% and 44.1% for patients receiving chemotherapy, steroids or other drugs, 64.1% and 56.1% for splenectomized patients and 88.9% (at 5 years) for alpha interferon (IFN)-treated patients (p < 0.0001). Our findings suggest that IFN has improved the prognosis of HCL, and that it must be considered a good initial treatment for patients with HCL.

Adult↗
PubMed1994

Possible significance of antibodies to Legionella pneumophila in HIV-1 infected patients with acute respiratory illness.

Eighty-six serum samples from 52 HIV-1 infected patients with complicating pneumonia illness were assayed for the presence of antibodies to Legionella pneumophila. In 25 of these patients Pneumocystic carinii has been previously diagnosed. Among all patients investigated only 4 had antibodies to L. pneumophila of significant titer of 128. In one patient L. pneumophila was demonstrated coexisting with P. carinii. Despite of a small proportion of patients with a significant titer of antibodies against L. pneumophila, the presence of this microorganism should be carefully investigated in AIDS patients with complicating pneumonia especially when the aetiological diagnosis is not defined; the reason is to improve the therapeutic treatment.

AIDS-Related Opportunistic Infections↗