Peripheral blood stem cell transplantation followed by recombinant alpha interferon for chronic myelogenous leukemia in chronic phase: preliminary results.
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Adolescent↗
Biomedical subjects
D Caillot
Publications and source records attributed to D Caillot.
Efficacy and tolerance of an amphotericin B lipid (Intralipid) emulsion in the treatment of candidaemia in neutropenic patients.
The efficacy and tolerance of a new amphotericin B lipid emulsion (AmB-IL) in which amphotericin B was diluted in a lipid solution for parenteral nutrition (Intralipid) was assessed in fourteen episodes of candidaemia occurring in neutropenic patients. The strains isolated were Candida krusei (nine cases), Candida albicans (three cases), Candida parapsilosis (one case) and Candida lusitaniae (one case). An AmB-IL was administered at a mean dosage of 1.18 mg/kg/day (range 0.73-1.55) for 22 days (range 6-62). Flucytosine was added to AmB-IL in 12 patients (mean duration 10.6 days). Chills were noted in only 3/306 infusions of AmB-IL. A mild increase of serum creatinine level from 9.3 +/- 3 mg/L (baseline) to 10.9 +/- 3 mg/L (after completion of AmB-IL) and mild decrease of creatinine clearance from 83 +/- 28 mL/min to 56 +/- 21 mL/min were observed. These changes did not correlate with either daily or total dose of AmB-IL or length of therapy. Seven patients were cured and six improved (patients who subsequently died due to nonfungal cause) with AmB-IL. One patient died due to C. krusei pneumonia. In conclusion AmB-IL is a well-tolerated method of amphotericin B administration. It could facilitate the use of amphotericin B without impairing its efficacy for the treatment of candidaemia in neutropenic patients.
Adult↗
Autologous blood stem-cell transplantation and recombinant interferon alfa in chronic myeloid leukemia.
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Adult↗
Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis.
OBJECTIVES: To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis. DESIGN: Non-blind randomised controlled trial. SETTING: University hospital; tertiary clinical care. PATIENTS: 22 HIV positive patients with oral candidiasis. INTERVENTIONS: Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion). MAIN OUTCOME MEASURES: Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin. RESULTS: 11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose. CONCLUSIONS: Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin.
AIDS-Related Opportunistic Infections↗
Prophylactic fluconazole and Candida krusei infection.
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Candidiasis↗
Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma.
Interleukin-6 (IL-6) was demonstrated to be a strong autocrine or paracrine plasmocytoma cell growth factor in humans. Using a bioassay, high serum IL-6 (S-IL-6) levels were correlated with disease severity in plasma cell dyscrasias. Since other cytokines could interfere with the bioassays, we developed a specific radioimmunoassay to study S-IL-6 levels in 102 patients with monoclonal gammopathy (MG). S-IL-6 level was studied by a double antibody radioimmunoassay using a rabbit polyclonal anti-IL-6 antibody and a human recombinant IL-6 as the standard. The lowest value of the standard significantly different from zero was found to be 78 pg/ml. Within-run and between-run precisions were characterized by a mean coefficient of variation of 3.72 and 5.5%, respectively. The mean analytical recovery was found to be 113% and the immunochemical identity of IL-6 standard and S-IL-6 was shown by dilution tests. IL-6 was detected in all tested sera. Sera from 66 healthy volunteers and 43 patients with acute leukemia or malignant lymphoma were tested as controls. In healthy subjects, S-IL-6 values were 294 +/- 86 pg/ml. MG were classified as multiple myeloma (MM), macroglobulinemia, and MG of undetermined significance (MGUS). The distribution of S-IL-6 levels in patients with MG was significantly higher than in healthy subjects but lower than in patients with acute leukemia or Hodgkin's lymphoma. Results obtained in 55 patients with MM were related to other biological parameters. S-IL-6 levels correlated with bone-marrow plasmacytosis (P less than .0005), serum-lactate dehydrogenase (S-LDH; P less than .005), serum beta 2 microglobulin (S -beta 2m; P less than .01), and serum calcium (S-Ca; P less than .025) and inversely correlated with haemoglobin (P less than .025). Our results indicate that 1) radioimmunoassay is suitable for the measurement of human IL-6 in serum; 2) high S-IL-6 levels are observed in a small number of patients with MG; and 3) S-IL-6 level correlates with tumour cell mass in patients with overt MM.
Bone Marrow↗
Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericin B.
In a retrospective study a new lipid-based delivery system for administration of amphotericin B was evaluated in 26 treatment courses in 22 patients. Amphotericin B was given by infusion diluted in either the lipid solution (1 mg/kg/d; 13 courses) or dextrose (0.92 mg/kg/d; 13 courses). No differences were noted in the serum pharmacokinetics. Fever or rigors were observed in 6 of 13 courses in the conventional amphotericin B group versus none in the lipid amphotericin B group (p = 0.007). Four of 13 courses of treatment were discontinued due to adverse effects in the conventional amphotericin B group compared to none in the other group (p = 0.048). In the lipid amphotericin B group the decrease in creatinine clearance was significantly lower on the fourth day of treatment (p = 0.04) and significantly fewer patients had a decrease of more than 25% in creatinine clearance on the sixth day (4/12 vs 9/11 p = 0.02). These preliminary findings suggest that this lipid amphotericin B formulation is well tolerated with few nephrotoxic effects.
Adult↗
New case of t(3;17)(q26;q22) as an additional change in a Philadelphia-positive chronic myelogenous leukemia in acceleration.
A new case of t(3;17)(q26;q22) was observed in a Philadelphia-positive (Ph+) chronic myelogenous leukemia in acceleration 1 month before occurrence of the blastic phase. Abnormal megakaryocytopoiesis and thrombopenia were noted, but blast cells did not express platelet markers. The same translocation was previously reported in three myeloproliferative disorders in acceleration or in the process of becoming acute. Translocations or inversions of chromosome 3 with breakpoint involving the band 3q26 were specifically associated with megakaryoblastic acute phase or abnormal megakaryocytopoiesis. This report confirms that the t(3;17)(q26;q22) is a specific nonrandom chromosomal abnormality associated with the acute nonlymphoblastic phase of myeloproliferative disorders and megakaryocytopoiesis dysfunction.
Bone Marrow↗
High concentrations of intrathecal interleukin-6 in human bacterial and nonbacterial meningitis.
Interleukin-6 (IL-6) is multipotent cytokine that acts in a network of factors directing the inflammatory reaction of purulent bacterial meningitis (PBM). However, little is known about the role of IL-6 in aseptic or "viral" meningitis (AM). IL-6 was assayed by RIA in cerebrospinal fluid (CSF) and serum samples obtained from patients with AM (n = 65), PBM (n = 8), and lymphocytic bacterial meningitis (LBM, n = 11). Of patients with AM, 89% had detectable IL-6 in CSF, with high IL-6 titers (median, 2160 pg/mL; 95% confidence interval [CI], 1320-2540 pg/mL) compared with 100% in patients with PBM (median, 6575 pg/mL; 95% CI, 450-32,000 pg/mL) and 90.9% in patients with LBM (median, 875 pg/mL; 95% CI, 150-2180 pg/mL). There was a highly symmetrical correlation between IL-6 and the percentage of polymorphonuclear cells in CSF of patients with PBM (r = .97, P = .01) and AM (r = .49, P = .002). In conclusion, this study shows evidence that IL-6 is released into the meningeal space in aseptic meningitis and is correlated with the local acute inflammatory response.
Humans↗
Feasibility of using quinine, a potential multidrug resistance-reversing agent, in combination with mitoxantrone and cytarabine for the treatment of acute leukemia.
PURPOSE: We demonstrated previously that sera from quinine-treated patients reversed the multidrug resistance (MDR) of a human leukemic cell line. We now report a phase I and II clinical study that examined the toxicity of the combination of quinine with mitoxantrone and cytarabine (Ara-C). PATIENTS AND METHODS: Fifteen adult patients with relapsed or refractory acute leukemia were treated with quinine formiate (30 mg/kg/d in continuous intravenous (IV) infusion from day 1 through day 5 or 6) associated with Ara-C (1 g/m2 in 3-hour IV infusion twice a day for 5 days) and five increasing doses of mitoxantrone (from 8 mg/m2/d for 4 days to 12 mg/m2/d for 5 days). RESULTS: The main toxicity was severe myelosuppression: the mean times to leukocyte recovery (> 500/microL), granulocytes recovery (> 500/microL), and platelet count recovery (> 50,000/microL) were 23 days (range, 17 to 29 days), 30.6 days (range, 17 to 48 days), and 35.4 days (range, 14 to 75 days), respectively. The nonhematopoietic toxicity of this regimen was acceptable. Nausea and vomiting were common, but severe mucositis was observed in only two patients. Cardiotoxicity was limited to transient episodes of moderate supraventricular tachycardia and a clinically well-tolerated bradycardia. Tinnitus and vertigo were observed in 10 cases (67%), and mild hearing loss and transient increase of serum bilirubin were observed in six patients (40%). Total quinine serum levels reached a steady-state concentration between 6.4 and 18 mg/L in 24 hours. Complete remission (CR) was achieved in eight of 14 (57%) assessable patients, and partial response (PR) was achieved in two additional patients (14%). P-glycoprotein expression was detected on blast cells from five of 13 studied patients before treatment. A response was observed in all P-glycoprotein-positive cases. CONCLUSION: Quinine can be used safely as a potential reversing agent of MDR for the treatment of clinically resistant acute leukemias.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Bone marrow necrosis and human parvovirus associated infection preceding an Ph1+ acute lymphoblastic leukemia.
A case of bone marrow necrosis associated with a serologically documented recent Parvovirus B 19 infection which preceded the development of PH1+ acute lymphoblastic leukemia is reported. No conclusions can be drawn on the basis of a single case but the question of the role of human Parvovirus B19 in the pathogenesis of bone marrow necrosis is discussed. It is suggested that the virus may act as a co-factor for the induction of bone marrow necrosis, in some cases.
Adult↗
[Burkitt's lymphoma: an exceptional cause of testicular tumor].
Based on a case of Burkitt's lymphoma presenting in the form of a testicular mass in a 66 year old man, the authors stress the importance of making the diagnosis as early as possible. This malignant lesion has one of the greatest capacities for proliferation and any delay in treatment can decrease the chances of curability of the tumour.
Aged↗
[Emulsion of amphotericin B in Intralipid 20%: in vitro and in vivo efficacy].
Toxic effects limit the use of amphotericin B (AmB) for the treatment of systemic Candida infections. In vitro and in vivo toxicity can be substantially reduced by mixing AmB with a lipid emulsion used for parenteral nutrition, intralipid 20% (IL). This study was designed to evaluate the potential effects of IL on the activity of Amphotericin B against Candida. A clinical strain of Candida albicans was used. AmB deoxycholate (Fungizone) was reconstituted in a 5% glucoce solution (AmB-G5), in 3 mg/ml IL (AmB-IL3) or in 1.5 mg/ml IL (AmB-IL 1.5). Minimum inhibitory concentrations and minimum lethal concentrations were 0.4 mg/l and 2.5 mg/l, respectively, with AmB-G5, 0.1 mg/l and 1 mg/l with AmB-IL3, and 0.24 mg/l and 1 mg/l with AmB-IL 1.5. In vitro killing curves with 0.1 mg/l, 0.25 mg/l, and 2.5 mg/l AmB were determined with the following results: 1) with 0.1 and 0.25 mg/l AmB, fungicidal activity was seen with AmB-IL3 and AmB-IL 1.5 but not with AmB-G5; 2) with 2.5 mg/l AmB, fungicidal activity was less marked with AmB-G5 (-1.7 log CFU/ml after 24 hours) than with AmB-IL3 and AmB-IL1.5 (-4.3 log CFU/ml and -4.2 log CFU/ml, respectively, after 24 hours; p less than 0.05). In rabbits given a single intravenous injection of 4 mg/kg AmB, analysis of infected subcutaneous fibrin clots detected measurable concentrations of AmB beyond the 24th-36th hour, with levels of 0.5 mg/l for AmB-G5 and 1 mg/l for the two AmB-IL preparations over a period of three days.(ABSTRACT TRUNCATED AT 250 WORDS)
Amphotericin B↗
Sufficient levels of quinine in the serum circumvent the multidrug resistance of the human leukemic cell line K562/ADM.
Reversal of multidrug drug resistance (MDR) has been achieved in vitro by a variety of agents including verapamil, quinidine, cyclosporine A, and amiodarone. The toxicity of these agents precludes the achievement of sufficient levels in the serum to circumvent efficiently the MDR in vivo. The authors previously demonstrated that quinine, the widely used antimalarial agent, is able to reverse primary resistance of rat colon cancer cells to anthracyclines. In this report, the efficiency of quinine formiate in reversing the doxorubicin (ADM) (Adriamycin, Adria Laboratories, Columbus, OH) resistance of the well-defined MDR human leukemic cell line K562/ADM was demonstrated. In culture medium, quinine is slightly less effective than verapamil in increasing the cytotoxicity and uptake of ADM when both drugs are used at the same concentration. A nontoxic dose of 5 micrograms/ml is necessary to reverse the MDR in K562/ADM cells. In patients receiving quinine formiate in a continuous intravenous infusion, a significant correlation (r = 0.84) was found between the serum levels of quinine and the ability of sera to increase ADM uptake in K562/ADM cells. When quinine is administered at a conventional dose (25 to 30 mg/kg/d), serum levels consistently reach more than 8 micrograms/ml without severe side effects; ear noises and vertigo are the dose-limiting side effects. At these concentrations, quinine induces a more than double increase in ADM uptake in K562/ADM cells. Pharmacokinetic data indicate that quinine should be administered 24 to 36 hours before anti-cancer drugs in clinical trials that test its efficiency as a modifier of MDR in human hematologic malignant neoplasms.
Doxorubicin↗
Imipenem/teicoplanin for Rhodococcus equi pulmonary infection in AIDS patients.
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Acquired Immunodeficiency Syndrome↗
P-glycoprotein expression and in vitro reversion of doxorubicin resistance by verapamil in clinical specimens from acute leukaemia and myeloma.
The expression of the P-glycoprotein which is associated with the development of multidrug resistance in various cell lines was investigated in 87 fresh acute leukaemia and multiple myeloma samples using the specific mouse monoclonal antibody MRK16 in an indirect immunofluorescence assay. Considering a 10% positive cell cut-off value, a heterogeneous expression of P-glycoprotein was observed in 5/22 (22.7%) de novo acute leukaemias, 7/22 (31.8%) relapse or secondary acute leukaemias, 14/27 (51.8%) acute transformation of myeloproliferative or myelodysplastic syndromes and 5/16 (31.2%) multiple myelomas. This expression was not associated with specific cytogenetic abnormalities, especially alterations of chromosome 7q. Verapamil, a calcium channel blocker, has been demonstrated to circumvent the multidrug resistance in cell lines, possibly by interfering with P-glycoprotein function. Using the microculture tetrazolium assay, verapamil was demonstrated to increase the sensitivity of fresh leukaemic or myeloma cells to doxorubicin in 19/43 (43.1%) samples. The doxorubicin IC50 level and the capacity of verapamil to increase the sensitivity of blast cells to doxorubicin in vitro did not correlate with the expression of P-glycoprotein. We conclude that high non-cytotoxic concentrations of verapamil were able to increase the in vitro doxorubicin sensitivity of fresh acute leukaemia and myeloma cells without detectable expression of the P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Paraneoplastic vasculitis and multiple myeloma].
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Aged↗
Synergism between cefotaxime and fosfomycin in the therapy of methicillin and gentamicin resistant Staphylococcus aureus infection in rabbits.
An experimental model of infected subcutaneous fibrin clots in rabbits was used to study the synergism between cefotaxime and fosfomycin in infection with methicillin and gentamicin resistant Staphylococcus aureus (MGRSA), and to determine the efficacy of a simplified schedule of administration. The bactericidal activity of cefotaxime and fosfomycin against MGRSA was investigated giving the drugs in one full or two divided doses either alone or in combination. The pharmacokinetics of the drugs were correlated with the antibacterial efficacy obtained over 12 hours of treatment. The results confirmed that the combination of cefotaxime and fosfomycin is highly synergistic in experimental MGRSA infection. Higher bactericidal activity was obtained with a regimen of 6-hourly drug administration which resulted in persistent levels of both drugs in serum as well as at the site of infection.
Analysis of Variance↗