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1.
Bone Marrow Transplant ; 26(1): 23-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10918402

ABSTRACT

This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN > or =0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt > or =30x10(9)/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0. 07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.


Subject(s)
Antiviral Agents/therapeutic use , Bone Marrow Transplantation , Cytomegalovirus Infections/prevention & control , Foscarnet/therapeutic use , Adult , Antiviral Agents/adverse effects , Blood Pressure , Body Weight , Bone Marrow Transplantation/mortality , Dose-Response Relationship, Drug , Foscarnet/adverse effects , Ganciclovir/therapeutic use , Humans , Lymphocyte Depletion , Prospective Studies , Survival Rate , Transplantation, Homologous
2.
Eur J Clin Pharmacol ; 52(5): 397-401, 1997.
Article in English | MEDLINE | ID: mdl-9272411

ABSTRACT

OBJECTIVE: To compare the pharmacokinetics of foscarnet administered as an infusion twice daily (BID) or thrice daily (TID), and to compare the effects on the electrolyte balance, cardiac and renal functions over a 3-week induction treatment of Cytomegalovirus (CMV) retinitis. METHODS: Pharmacokinetics/dynamics of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS patients with CMV retinitis completed the investigation period. Concentrations of foscarnet and electrolytes were assayed by high-performance liquid chromatography (HPLC) and by an ion-selective analyser, respectively. RESULTS: The pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma and creatinine clearances were 2.0 and 1.6 ml.min-1.kg-1, respectively, in the BID group at steady state (day 21). In the TID group the corresponding values were 1.8 and 1.7 ml.min-1.kg-1, respectively. In both regimens the elimination half-life of foscarnet was 2-3 h. Ionized calcium concentrations were transiently decreased and strongly inversely correlated to foscarnet plasma concentrations in both regimens with no significant differences between groups. A trend towards prolongation of the QTc interval was seen when data from both treatments were analysed together. CONCLUSION: Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period.


Subject(s)
AIDS-Related Opportunistic Infections/metabolism , Antiviral Agents/pharmacokinetics , Cytomegalovirus Retinitis/metabolism , Foscarnet/pharmacokinetics , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/physiopathology , Adolescent , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Calcium/blood , Cytomegalovirus Retinitis/drug therapy , Cytomegalovirus Retinitis/physiopathology , Electrocardiography , Female , Foscarnet/administration & dosage , Foscarnet/adverse effects , Foscarnet/therapeutic use , Humans , Kidney Function Tests , Male
3.
Bone Marrow Transplant ; 18 Suppl 2: 110-4, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8932810

ABSTRACT

Thirty two allogeneic bone marrow transplant (BMT) recipients, aged 16-55 (median 35), with CMV antigenemia (= > 5 positive cells) developing at a median interval from BMT of 49 days, were given combined treatment with foscarnet and ganciclovir for 15 days. Maintenance was given with foscarnet and ganciclovir on alternate days for an additional 2 weeks. 31/32 patients were on cyclosporin 30 on systemic antibiotics and 9 were on intravenous amphotericin Median laboratory values on day 1 and 15 of treatment were respectively creatinine 1.0-1.1 mg%; WBC 5.7-4.1 x 10(9)/l; platelets 78 72 x 10(9)/l. All patients cleared CMV-antigenemia by day +15, though 5 reactivated on and 14 off maintenance: the dose of foscarnet (but not ganciclovir) received in the first 15 days was significantly lower in patients reactivating within 30 days (p = 0.0002). Six patients died, one with i.p., one with multiorgan failure, and four with infections. Eighteen patients survive 119-1051 days post-transplant. The actuarial TRM at 1 year is 23%. This study shows that combined foscarnet-ganciclovir is one therapeutic option for allogeneic BMT recipients developing CMVAg-emia with a high number of CMVAg+ cells: treatment can be given together with cyclosporin and antibiotics with appropriate dose reductions; it produces prompt clearing of CMV infection, and may reduce transplant related mortality when compared to single agent therapy.


Subject(s)
Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Foscarnet/administration & dosage , Ganciclovir/administration & dosage , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Adult , Cytomegalovirus Infections/etiology , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Transplantation, Homologous
4.
Transplantation ; 62(3): 376-80, 1996 Aug 15.
Article in English | MEDLINE | ID: mdl-8779686

ABSTRACT

In a previous study, we showed that patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT) who had cytomegalovirus (CMV) antigenemia with more than 4 CMV antigen-positive cells/200,000 have a high transplant-related mortality (TRM) rate, despite treatment with ganciclovir or foscarnet. In an attempt to reduce TRM, 32 allogeneic HSCT recipients, between the ages of 16 and 55 years (median, 35 years), with CMV antigenemia (> or = 5 positive cells) developing at a median interval from HSCT of 49 days, were given combination treatment with foscarnet and ganciclovir for 15 days. The prescribed dose was 180 mg/kg/day of foscarnet and 10 mg/kg/day of ganciclovir: the median administered dose in the first 15 days, after adjusting for creatinine levels and peripheral blood counts, was 64% for foscarnet and 53% for ganciclovir. Maintenance was given with foscarnet and ganciclovir on alternate days for an additional 2 weeks. Thirty-one of 32 patients were on cyclosporine, 30 were on systemic antibiotics, and 9 were on intravenous amphotericin. Median laboratory values on days 1 and 15 of treatment were 1.0 and 1.1 mg/100 ml creatinine, 5.7 x 10(9)/L, and 4.1 x 10(9)/L white blood cells, and 78 x lO(9)/L and 72 x 10(9)/L platelets. All patients cleared CMV antigenemia by day +15, although CMV antigenemia recurred in 5 patients on maintenance therapy and in 14 patients off maintenance therapy: the dose of foscarnet (but not ganciclovir) received in the first 15 days was significantly lower in patients in whom antigenemia recurred within 30 days (P=0.0002). Six patients died, one with interstitial pneumonia, one with multiorgan failure, and four with infections. Twenty-six patients survived 119-1051 days after transplant. The actuarial TRM rate at 1 year is 23%. Eighteen patients who had received unmanipulated bone marrow transplants from HLA-identical siblings were compared with 15 matched controls who had been treated with a single drug (either foscarnet or ganciclovir) for CMV antigenemia (> or = 5 cells): the actuarial 1 year TRM rate was 13% for patients receiving combined treatment, compared with 47% for controls receiving a single drug (P=0.02). This study shows that combined foscarnet-ganciclovir is one therapeutic option for allogeneic HSCT recipients who develop CMV antigenemia with a high number of CMV antigen-positive cells. Treatment can be given together with cyclosporine and antibiotics with appropriate dose reductions. It produces prompt clearing of CMV infection, and may reduce TRM rates in comparison to single-agent therapy.


Subject(s)
Cell Transplantation , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/etiology , Foscarnet/therapeutic use , Ganciclovir/therapeutic use , Hematopoietic Stem Cells , Adolescent , Adult , Antibodies, Viral/analysis , Cell Transplantation/mortality , Cyclosporine/therapeutic use , Cytomegalovirus/immunology , Cytomegalovirus/physiology , Drug Therapy, Combination , Feasibility Studies , Female , Foscarnet/adverse effects , Humans , Male , Middle Aged , Pilot Projects , Transplantation, Homologous , Virus Activation
5.
Bone Marrow Transplant ; 13(6): 753-8, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7920310

ABSTRACT

Twenty-five patients with hematologic malignancies (n = 21) or aplastic anemia (n = 4) undergoing an allogeneic BMT from an HLA-identical sibling developed cytomegalovirus (CMV) antigenemia at a mean interval from BMT of 41 days (range 16-141 days). All patients were treated at the time of antigenemia in the absence of other signs of CMV disease with ganciclovir (n = 13) or foscarnet (n = 12) if the WBC count was < 2.5 x 10(9)/l or the patient had aplastic anemia. The two groups were comparable for age, sex and disease status. There were more patients receiving T cell-depleted grafts in the foscarnet group (58% vs 15%, p = 0.003). The first course of treatment was planned to last a minimum of 10 days: foscarnet was given at 180 mg/kg/day, and ganciclovir at 10 mg/kg/day. Patients still showing pp65-positive cells continued treatment in the absence of adverse effects such as cytopenia and/or increased creatinine levels. Maintenance treatment was given for 3-4 weeks. End-points of the study were (1) clearing of CMV antigenemia, (2) tolerance and side-effects, and (3) progression to CMV disease. Both agents were effective in clearing CMV antigenemia: 14 of 25 patients were CMV antigen-negative by day 14 of treatment and all surviving patients were negative by day +50. Renal toxicity was seen mainly in the foscarnet group but caused discontinuation of the drug only in one patient. Myelotoxicity was seen in the ganciclovir group and again could be controlled in 12 of 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Bone Marrow Transplantation/adverse effects , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/etiology , Foscarnet/therapeutic use , Ganciclovir/therapeutic use , Adult , Anemia, Aplastic/therapy , Antigens, Viral/analysis , Antigens, Viral/immunology , Cytomegalovirus/immunology , Cytomegalovirus Infections/immunology , Female , Foscarnet/administration & dosage , Foscarnet/adverse effects , Ganciclovir/administration & dosage , Ganciclovir/adverse effects , Humans , Immunoglobulin M/blood , Leukemia/therapy , Male , Transplantation, Homologous
6.
Bone Marrow Transplant ; 13(6): 783-8, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7920315

ABSTRACT

Eleven patients underwent bone marrow transplant (BMT) from an HLA-identical sibling following single dose total body irradiation (TBI), with in vivo and ex vivo T cell depletion (TCD). In spite of CMV prophylaxis with acyclovir and high-dose i.v. Ig, 10 of 11 patients developed CMV antigenemia, at a median interval from BMT of 34 days (range 16-72 days) and five died with CMV disease. Foscarnet was then given prophylactically in 11 additional TCD patients to test whether we could (1) prevent CMV reactivation, and (2) reduce transplant-related mortality. Foscarnet was given daily from days +10 to +15 (180 mg/kg/day), then thrice weekly (90 mg/kg/day) until day +100. Five patients developed CMV antigenemia at a median interval from BMT of 42 days (range 16-65 days); one progressed to CMV pneumonitis and died. The risk of developing CMV antigenemia within day 100 is currently 91% for the historical control group and 45% for the foscarnet group (p = 0.005). At diagnosis of CMV, the median number of CMV antigen-positive cells was 6.5 (range 1-13) vs 1 (range 1-5) in acyclovir vs foscarnet patients (p = 0.02) and the median highest number of CMV antigen-positive cells was 7 (range 3-110) vs 1 (range 1-12), respectively, (p = 0.03). The actuarial 1 year transplant-related mortality (TRM) is 49% and 13% in the two groups (p = 0.08). This study suggests that foscarnet prophylaxis starting on day +10 post-BMT may be helpful in reducing the risk of CMV disease and early mortality following TCD BMT.


Subject(s)
Bone Marrow Transplantation/adverse effects , Cytomegalovirus Infections , Foscarnet/therapeutic use , Acyclovir/adverse effects , Acyclovir/therapeutic use , Adult , Bone Marrow Transplantation/immunology , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/prevention & control , Dose-Response Relationship, Drug , Female , Foscarnet/adverse effects , Humans , Male , Middle Aged , Pilot Projects , Risk Factors , Transplantation, Homologous
7.
Boll Ist Sieroter Milan ; 68(1): 51-6, 1989.
Article in English | MEDLINE | ID: mdl-2491286

ABSTRACT

In this work we reported the results obtained using two ELISA-tests (the seropositivity was confirmed by Western-Blot) for detection of HIV-Ab in normal and at risk population (according by the classification from C.D.C. 1982) exposed to screening for various, sanitary measures. Our results concerning the percentage of seropositivity to HIV-Ab in drug-addicts (49%) are in agreement with the results obtained in the most qualified Italian Centres. The incidence of congenital infection is high, pointed 50%; the 100% of seropositive children were infected by drug-addicts seropositive parents. Casuistry among haemophilic patients we have demonstrated a greater seropositivity in B haemophilic subjects than A haemophilic ones. The seropositivity (24%) verified among prisoners is totally related to drug-addiction. Prevalence of seropositivity among heterosexual partners of HIV positive subjects was 22% among female partners of infected men, and 9% among male partners of infected women. Checking performed upon nursing staff who casually were contaminated by seropositive patient's blood confirmed 100% of seronegativity after eight months. No seropositive subjects were performed in every not a risk group.


Subject(s)
HIV Infections/epidemiology , Adult , Female , HIV Antibodies/blood , HIV Infections/complications , HIV Infections/congenital , HIV Infections/transmission , Hemophilia A/complications , Homosexuality , Humans , Infant, Newborn , Italy/epidemiology , Male , Personnel, Hospital , Pregnancy , Pregnancy Complications, Infectious , Prevalence , Prisoners , Risk Factors , Sex Work , Sexual Behavior , Substance Abuse, Intravenous/complications
9.
Microbiologica ; 11(1): 1-5, 1988 Jan.
Article in English | MEDLINE | ID: mdl-2832708

ABSTRACT

A new cell line, obtained by co-cultivation of fetal lamb kidney cells and lymphocytes collected from an adult calf affected by enzootic bovine leukemia, was studied for bovine leukemia virus (BLV) morphogenesis. In this new cell line, called FLK-BLV, persistently infected with BLV, we identified extracellular and intracellular BLV particles. We never observed "budding" particles along the cell surface, and therefore assumed it was a new BLV maturation process in the cell vacuoles. In fact we found mature and non-mature particles connected with the cell-membrane system or cellular debris within vacuoles. We suggest that the viral envelope could be supplied by vacuole membrane. In our samples we also observed a cytopathic effect with syncytia formations similar to those observed on other BLV-producing cell lines.


Subject(s)
Leukemia Virus, Bovine/growth & development , Retroviridae/growth & development , Animals , Cattle , Cell Line , Cell Membrane/microbiology , Cytopathogenic Effect, Viral , Cytoplasm/microbiology , Kidney , Leukemia Virus, Bovine/ultrastructure , Lymphocytes , Microscopy, Electron , Morphogenesis , Sheep , Vacuoles/microbiology , Virus Cultivation
10.
Boll Ist Sieroter Milan ; 65(5): 354-6, 1986.
Article in Italian | MEDLINE | ID: mdl-3493791

ABSTRACT

The authors are herewith reporting the results of an immunological screening performed on 15 drug addicts presenting serological positivity for anti HTLV III (Elisa and WB). The study has been carried out determining populations and subpopulations of lymphocytes (T3, T4, T8 and T4/T8) and performing cutaneus tests with multiple antigens (Tetanus--Candida--Diphtheria--Proteus--Streptococcus and Tricophyton). The results achieved by mean of the above mentioned tests seem to indicate the presence of an immunodeficit hitting mainly the cell-mediated immunity in all the patients examined.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , Opioid-Related Disorders/immunology , T-Lymphocytes/classification , Adolescent , Adult , Female , Humans , Male , Skin Tests
16.
Boll Ist Sieroter Milan ; 64(3): 195-200, 1985.
Article in Italian | MEDLINE | ID: mdl-4041243

ABSTRACT

The authors have evaluated comparatively the diagnostic reliability of the most recent RIA and ELISA mono-polyclonal techniques for the determination of HBsAg in serum by means of in vivo and in vitro tests. Statistically, no difference has been found as regards the various methods.


Subject(s)
Hepatitis B Surface Antigens/analysis , Reagent Kits, Diagnostic , Enzyme-Linked Immunosorbent Assay , Hepatitis B Antibodies/analysis , Humans , Radioimmunoassay
17.
Boll Ist Sieroter Milan ; 64(1): 59-69, 1985.
Article in Italian | MEDLINE | ID: mdl-4005060

ABSTRACT

The authors have investigated the immunological picture in one group of patients affected by immune mediated diseases treated with lymphoplasmapheresis. The immunomodulatory effects of the therapy were controversial after a single procedure, paradoxical after a complete cycle of 4 procedures.


Subject(s)
Immune System Diseases/therapy , Leukapheresis , Lymphocytes/classification , Cell Separation , Humans , Plasma Exchange
20.
Boll Ist Sieroter Milan ; 63(6): 529-33, 1984.
Article in Italian | MEDLINE | ID: mdl-6534398

ABSTRACT

The authors have evaluated the effects of specific Immunoglobulins administration in order to prevent type B viral hepatitis. 34 members of care units entered a program of epidemiological surveillance after an occasional contamination with biological samples obtained from patients affected by type B viral hepatitis. All these subjects have been treated with two injections of specific immunoglobulins at the dose of 0.06 ml/kg. i.m.; the first was administered immediately after contamination and the second after one month. Serum antibody titres were determined by RIA techniques in a six months follow-up. The results seem to indicate that the degree of protectivity after passive immunization is poor and rather incostant.


Subject(s)
Hepatitis B Antibodies/analysis , Hepatitis B/prevention & control , Immunization, Passive , Female , Hepatitis B/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B e Antigens/analysis , Hepatitis B e Antigens/immunology , Humans , Male
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