Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149514 (bronchitis)
 6,902 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA). Twenty-one courses of DCF were administered to 13 patients ranging in age from 15 to 78 yr. Eight patients had T-cell disorders, and five patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5 to 30 mg/sq m/day, and the duration of the courses ranged from 1 to 5 days. The DCF plasma half-life ranged from 4.9 to 6.2 hr and was independent of dose. The dose-limiting toxicities involved the central nervous system (CNS) and the kidneys. Other toxicities included bronchitis, decreases in hematocrit, arthralgias, and myalgias. Mortality was encountered in three patients. These toxic effects may have been secondary to the accumulation of the metabolites adenosine and deoxyadenosine. Deoxyadenosine and adenosine were both detectable in plasma (10(-6) M) and in urine (10(-3) M). Two partial remissions were observed: one in a patient with T-cell ALL and another in a patient with mycosis fungoides. Minimal responses characterized by either declines in peripheral blast counts or partial resolution of adenopathy were observed in five other patients. No responses were observed in six patients. These observations suggest that DCF is effective in the treatment of T-cell lymphoid malignancies.
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PMID:Clinical pharmacology of deoxycoformycin. 626 81

An adenosine deaminase (ADA) deficient patient with severe combined immunodeficiency (SCID) developed resistance to therapeutic injections of bovine ADA conjugated to polyethylene glycol (PEG-ADA). This 18-year-old girl was diagnosed as having partial ADA deficiency at age 7 years, and was started on bovine conjugated PEG-ADA at age 15 years. The weekly dose of 15 U/kg led to clinical improvement with resolution of sinusitis and bronchitis within 2 months and normalization of some T cell functions. After 5 months, however, she developed an inhibitory antibody to ADA, became refractory to treatment with PEG-ADA, and clinically and immunologically deteriorated. This antibody was successfully suppressed over a 4-month period with a combination of prednisone (2 mg/kg/day), intravenous immunoglobulin (2 g/kg/dose), and discontinuing the PEG-ADA injections for 7 weeks. The PEG-ADA injections were then restarted at a higher dose (20 U/kg/dose, twice a week). With the suppression of the inhibitory antibody, her clinical and immunologic status improved to previously achieved level. She has subsequently continued treatment for over 36 months, receiving a single weekly dose of PEG-ADA (20 U/kg/week) with sustained clinical and immunologic improvement, including weakly positive antigen-specific T cell proliferative responses to tetanus and Candida.
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PMID:Suppression of an antibody to adenosine-deaminase (ADA) in an ADA-deficient patient receiving polyethylene glycol modified adenosine deaminase. 850 39

Loss of adenosine deaminase activity leads to severe combined immunodeficiency (ADA-SCID); production and function of T, B, and natural killer (NK) cells are impaired. Gene therapy (GT) with an autologous CD34+-enriched cell fraction that contains CD34+ cells transduced with a retroviral vector encoding the human ADA cDNA sequence leads to immune reconstitution in most patients. Here, we report short- and medium-term safety analyses from 18 patients enrolled as part of single-arm, open-label studies or compassionate use programs. Survival was 100% with a median of 6.9 years follow-up (range, 2.3 to 13.4 years). Adverse events were mostly grade 1 or grade 2 and were reported by all 18 patients following GT. Thirty-nine serious adverse events (SAEs) were reported by 15 of 18 patients; no SAEs were considered related to GT. The most common adverse events reported post-GT include upper respiratory tract infection, gastroenteritis, rhinitis, bronchitis, oral candidiasis, cough, neutropenia, diarrhea, and pyrexia. Incidence rates for all of these events were highest during pre-treatment, treatment, and/or 3-month follow-up and then declined over medium-term follow-up. GT did not impact the incidence of neurologic/hearing impairments. No event indicative of leukemic transformation was reported.
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PMID:Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety. 2943 35