cefoxitin and Leukemia

Physical and chemical nature of the T and Tn pancarcinoma [CA] glycopeptide epitopes [EPs], which are immediate precursors of the blood group MN EPs, and their role in CA pathogenesis and in clinical disease are discussed. T/Tn are immuno-occluded in non-CA diseased and in healthy tissues. Well-differentiated CAs usually express a higher proportion of T than Tn EPs, while Tn predominates in poorly differentiated primary CAs. Measurement of density of T and Tn EP expression on primary breast CA permits disease prognostication. CA-T and -Tn are cell adhesion molecules involved not only in invasion but also in metastasis. Immunological methods readily detect in vivo autoimmune responses to CA-T and -Tn EPs in about 90% of all CA patients from incipience and throughout. Everyone has preexisting anti-T and anti-Tn antibodies [Abs] induced by the intestinal flora. T/anti-T immunoassays are highly efficient in detection of incipient and clinically overt CAs and, importantly, predicted CA in 77% of the patients, months to many years before their biopsy/X-ray turned positive; there were no false immune predictions of CA. Since 1974, we use human O MN red cell-derived T/Tn glycoprotein vaccine plus adjuvants successfully in safe, specific, effective, long-term, active immunotherapy against recurrence of advanced breast CA pTNM Stages IV, III, and II.

Topics: Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Biopsy; Breast Neoplasms; Cell Adhesion; Epitopes; Erythrocyte Membrane; Female; Humans; Hypersensitivity, Delayed; Immunotherapy; Leukemia; Lymphoma; Recurrence

Cefoxitin (CFX) at a daily dose of 3 to 12 grams was administered to patients who had hematopoietic disorders as underlying diseases and having severe infections. Efficacy and safety of the drug were evaluated. The underlying diseases in the 64 patients included in the evaluation of efficacy were acute myelocytic leukemia (30 cases), acute lymphocytic leukemia (9), acute promyelocytic leukemia (3), acute monocytic leukemia (2), chronic myelocytic leukemia-blastic crisis (10), erythroleukemia (2), malignant lymphoma (2), aplastic anemia (2), and others (4). The infections were septicemia in 3 patients, suspected septicemia in 47, respiratory tract infections in 7, oral infections in 3, urinary tract infections in 2, and others in 2. The clinical efficacy of CFX was 'excellent' in 13 patients, 'good' in 26, 'fair' in 6, 'poor' in 19 for an efficacy rate of 60.9%. The efficacy rate classified according to infections was 66.7% in septicemia, 66.0% in suspected septicemia, 42.9% in respiratory tract infections and 66.7% in oral infection. The organisms isolated from the patients with septicemia were E. coli in 2 patients and B. cereus in 1. B. cereus was not susceptible to CFX. The efficacy rate was 60.0% in the 10 patients whose causative organisms were identified and 61.1% in the 54 patients whose causative organisms were not identified. There was no significant difference in the efficacy rate between the patients who had failed to respond to prior antibiotic therapy and those treated with CFX from the beginning. The efficacy rates for the former group (23 patients) and for the latter group (41 patients) were 56.5% and 63.4%, respectively. The efficacy rate in patients with an initial neutrophil count less than 500/mm3 (35 cases) and from 501 to 1,000/mm3 (13 cases) were 57.1% and 76.9%, respectively. Side effects which might have been caused by CFX were skin eruptions in 2 patients (2.6%) and transient elevation of GOT and GPT in 1 patient (1.3%) among 76 patients who were evaluated for safety. CFX was considered to be a markedly useful and safe drug in the treatment of patients with hematopoietic disorders who developed severe infections.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Cefoxitin; Child; Clinical Trials as Topic; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Respiratory Tract Infections; Sepsis

CD175 or Tn antigen is a carbohydrate moiety of N-acetylgalactosamine (GalNAc)α1-O- linked to the residue of amino acid serine or threonine in a polypeptide chain. Despite the chemical simplicity of the Tn antigen, its antigenic structure is considered to be complex and the clear determinants of Tn antigenicity remain poorly understood. As a consequence, a broad variety of anti-Tn monoclonal antibodies (mAbs) have been generated. To further investigate the nature and complexity of the Tn antigen, we generated seven different anti-Tn mAbs of IgM and IgG classes raised against human Jurkat T cells, which are Tn-positive due to the low activity of T-synthase and mutation in specific chaperone Cosmc. The binding analysis of anti-Tn mAbs with the array of synthetic saccharides, glycopeptides and O-glycoproteins revealed unexpected differences in specificities of anti-Tn mAbs. IgM mAbs bound the terminal GalNAc residue of the Tn antigen irrespective of the peptide context or with low selectivity to the glycoproteins. In contrast, IgG mAbs recognized the Tn antigen in the context of a specific peptide motif. Particularly, JA3 mAb reacted to the GSPP or GSPAPP, and JA5 mAb recognized specifically the GSP motif (glycosylation sites are underlined). The major O-glycan carrier proteins CD43 and CD162 and isoforms of CD45 expressed on Jurkat cells were precipitated by anti-Tn mAbs with different affinities. In summary, our data suggest that Tn antigen-Ab binding capacity is determined by the peptide context of the Tn antigen, antigenic specificity of the Ab and class of the immunoglobulin. The newly generated anti-Tn IgG mAbs with the strong specificity to glycoprotein CD43 can be particularly interesting for the application in leukemia diagnostics and therapy.

Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal, Murine-Derived; Antibody Specificity; Antigens, CD; Antigens, Tumor-Associated, Carbohydrate; Binding, Competitive; Humans; Immunoglobulin G; Immunoglobulin M; Jurkat Cells; Leukemia; Membrane Glycoproteins; Mice; Molecular Chaperones; Molecular Sequence Data; Mucin-1; Peptide Fragments; Protein Binding; Recombinant Proteins

Morniga G is a plant lectin selective for high density of tumor-associated carbohydrate T and Tn antigens on the surface of cells. The interaction of the protein with Tn induces its cell penetration. This property was used for targeting photosensitizers (consisting of the porphyrins TrMPyP and TPPS, the Al(III)-phthalocyanin AlPcS(4), and the chlorin e6) against leukemic Jurkat T cells after covalent coupling to the protein. The control of MornigaG/photosensitizer loading allowed the comparison of the toxicity of the different photosensitizer conjugates. Conjugate including a single AlPcS(4) per protein appeared promising, since it is poorly toxic when irradiated under white light, while it shows a strong phototoxicity (LD(50) = 4 nM) when irradiated in the therapeutic window, it preferentially kills cancerous lymphocytes, and the sugar binding specificity of the lectin part of the molecule remains unaltered.

Topics: Antigens, Tumor-Associated, Carbohydrate; Cell Death; Drug Delivery Systems; Hemagglutination; Humans; Jurkat Cells; Leukemia; Photochemotherapy; Photosensitizing Agents; Plant Lectins

Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high affinity tumor-associated T and Tn antigens. The conjugation allowed a quick uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced phototoxicity. The present study was performed: (i) to evaluate the targeting potential of the conjugate towards tumor and normal cells and its phototoxicity on various leukemia cells, (ii) to investigate the mechanism of conjugate-mediated cell death. The conjugate: (i) strongly increased (×1000) the PS phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent process; (ii) specifically purged tumor cells from a 1∶1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes; (iii) was effective against various leukemic cell lines with distinct phenotypes, as well as fresh human primary acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase-independent cell death, which might be an advantage as tumor cells often resist caspase-dependent cell death. Altogether, the present observations suggest that conjugation with plant lectins can allow targeting of photosensitizers towards aberrant glycosylation of tumor cells, e.g. to purge leukemia cells from blood and to preserve the normal leukocytes in extracorporeal photochemotherapy.

Topics: Antigens, Tumor-Associated, Carbohydrate; Apoptosis; Caspases; Cell Line; Cell Line, Tumor; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; HL-60 Cells; Humans; Jurkat Cells; K562 Cells; Leukemia; Photochemotherapy; Photosensitizing Agents; Plant Lectins; Porphyrins; U937 Cells

Topics: Adult; Amikacin; Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Cefoxitin; Device Removal; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multiple Myeloma; Mycobacterium; Mycobacterium Infections; Retrospective Studies

A clinical investigation was made on the concurrent use of amikacin (AMK) and cefoxitin (CFX) against complicated infections with hematological disorders. The results obtained were summarized as follows: Eleven patients were treated with AMK and CFX. Clinical responses were excellent in 2 (18%), good in 4 (36%), fair in 1 (9%), and poor in 4 (36%), with an efficacy rate of 64%. No significant side effects requiring cessation of the treatment were observed.

Topics: Adolescent; Adult; Aged; Amikacin; Bacterial Infections; Cefoxitin; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Middle Aged

One hundred fifty-five patients with 157 febrile episodes were treated with amdinocillin or amdinocillin and cefoxitin as second-line therapy, or amdinocillin and ticarcillin or carbenicillin as initial therapy in three separate studies. Overall responses were 57 percent, 55 percent, and 54 percent for amdinocillin, amdinocillin-cefoxitin, and amdinocillin-ticarcillin or amdinocillin-carbenicillin, respectively. In all three studies, patients with septicemia responded less often than patients with other infections. Most patients were profoundly neutropenic at the initiation of therapy, and both the initial neutrophil level and neutrophil trend during therapy influenced response. A significant number of superinfections occurred when amdinocillin alone was used. Although amdinocillin, alone or in combination with cefoxitin, appeared effective as second-line therapy in infections with organisms shown sensitive in vitro, the combination of amdinocillin and ticarcillin or carbenicillin was only moderately effective in initial therapy for neutropenic, febrile, cancer patients.

Topics: Acute Disease; Adolescent; Adult; Aged; Amdinocillin; Bacterial Infections; Carbenicillin; Cefoxitin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukocyte Count; Male; Middle Aged; Neutrophils; Penicillanic Acid; Penicillins; Sepsis; Ticarcillin

The authors report 57 febrile episodes in 36 patients with leukemia and lymphoma. Patients with less than 1000 granulocytes and fever above 38.5 degrees C were included in this empirical antibacterial protocol (15 mg amikacin/kg/day/iv, 500 mg carbenicillin/kg/day/iv, 200 mg cefoxitin/kg/day/iv). The criteria for diagnosis of infection were those widely accepted [Schimpff et al. 1971]. Microbiologic documentation of infection was performed in 33.4% of febrile episodes. Antibacterial therapy induced an improvement in 75.1% of cases. Clinical response often occurred in the presence of profound granulocytopenia (in 72% of episodes). Therapy failure was higher in pneumonia (46%) and lower in fever of unknown origin (21%).

Topics: Adult; Aged; Agranulocytosis; Amikacin; Bacterial Infections; Carbenicillin; Cefoxitin; Drug Therapy, Combination; Female; Fever; Humans; Kanamycin; Leukemia; Lymphoma; Male; Middle Aged

Ten inpatients at the Second Department of Internal Medicine, Mie University Hospital, developed infections in the course of treatment for hematopoietic disorders and were administered cefoxitin (CFX). Patients suffered from the following infections: pharyngitis, 2; bronchitis, 2; pneumonia, 2; sepsis, 2; bacteremia, 1; suspected cases of bacteremia, 2; and fever of unknown origin, 1. The number of infections totaled 12 as 1 patient with pharyngitis also developed sepsis and 1 patient with pneumonia developed bacteremia. Duration for the administration of CFX ranged between 5 and 18 days with a total dosage of between 30 and 108 g. Of the 10 patients treated with CFX, 9 were treated concomitantly with micronomicin (MCR), doxycycline (DOXY), or sulbenicillin (SBPC), some were treated concomitantly with only 1 of the drugs and some were treated concomitantly with 2 of the drugs. The following clinical results were obtained: Following treatment, 4 patients were considered "excellent", 5, "good", and 3, "poor". Clinical efficacy rate was 75%. Four strains of Gram-positive cocci (1 strain of S. aureus, 2 strains of S. epidermidis and 1 strain of Streptococcus sp.) and 3 strains of Gram-negative rods (2 strains of P. aeruginosa and 1 strain of E. cloacae) were found in the clinical specimens of the 10 patients. These results differed somewhat from reported data that Gram-negative rods such as E. coli, Klebsiella sp., Pseudomonas sp., Serratia sp., are dominant. No serious side effects requiring cessation of treatment were observed. Elevations in the levels of S-GOT, S-GPT, serum alkaline phosphatase, blood urea nitrogen, etc. were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cefoxitin; Drug Evaluation; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multiple Myeloma

Ten patients with sepsis and pneumonia complicated by leukemia or lung cancer were treated with cefoxitin (CFX) at daily dose of 6 g. The following results were obtained. 1. Clinical effects of CFX were good in 5 patients, fair in 2 and poor in 3 with effective rate of 50%. 2. Out of 8 patients with sepsis, 5 showed good response to CFX and effective rate was 62.5%. 3. Bacteriological outcomes were eradicated in 1, unchanged in 1, replaced in 2 and unknown in 6 cases. 4. Diarrhea was observed in 1 patient but this was not considered related to CFX therapy. 5. No abnormal laboratory finding due to CFX was observed. 6. It should be considered that 6 g or more of CFX is given in case of severe infections, such as sepsis or pneumonia complicated by serious underlying diseases.

Topics: Adult; Aged; Cefoxitin; Drug Evaluation; Female; Humans; Infusions, Parenteral; Leukemia; Lung Neoplasms; Male; Middle Aged; Pneumonia; Sepsis

Cefoxitin (CFX) was administered to 12 patients for evaluation of clinical effects of CFX against secondary infections complicated with hematopoietic malignancies, and the following results were obtained. 1. The clinical effects were excellent in 1 and good in 8 out or 11 cases with efficacy rate of 81.8%. Out of 12 cases treated with CFX, 1 case was excluded from clinical evaluation because of prophylactic use. It is noted that all cases with pyelitis showed good response to CFX. 2. The serum levels of CFX were determined in 1 patient with renal failure. After intravenous drip infusion of 2 g in 200 ml of glucose solution, the serum concentrations were 67.2 micrograms/ml and 7.53 micrograms/ml at 14 hours and 24 hours (after hemodialysis), respectively. 3. No side effects attributed to CFX were observed. These results indicate that CFX is an effective and safe antibiotic for the treatment of severe infections accompanying hematopoietic malignancies.

Topics: Adult; Bacterial Infections; Cefoxitin; Drug Evaluation; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multiple Myeloma

Topics: Acute Disease; Adult; Amikacin; Bacterial Infections; Cefoxitin; Drug Therapy, Combination; Humans; Infusions, Parenteral; Kanamycin; Leukemia; Lincomycin; Middle Aged; Penicillins; Ticarcillin