pentostatin and Conjunctivitis

Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), was explored for its antineoplastic potential in 28 patients with advanced lymphoid malignancy. Both normal and malignant B lymphocytes have low levels of ADA activity, and low doses of dCF profoundly inhibit this enzyme in the peripheral blood of patients with chronic lymphocytic leukemia (CLL). The low doses of dCF administered in this trial (4 mg/m2) were not associated with prohibitive toxicity. Five of 28 patients had an objective response. Four additional patients had clinical improvement. No significant difference in the pretreatment ADA activity existed between responding patients and treatment failures. The demonstration of responses to dCF following failure on standard alkylating agents suggests that dCF may not be cross-resistant with current agents used to treat CLL. Additional studies should be pursued using low-dose dCF in patients with advanced malignancy.

Topics: Adenosine Deaminase Inhibitors; B-Lymphocytes; Candidiasis; Coformycin; Conjunctivitis; Drug Administration Schedule; Gastrointestinal Diseases; Herpesviridae Infections; Humans; Leukemia, Lymphoid; Liver Function Tests; Lymphoma, Non-Hodgkin; Middle Aged; Nucleoside Deaminases; Pentostatin; Respiratory Tract Infections; Ribonucleosides

Seventeen patients with acute leukaemia refractory to conventional chemotherapeutic agents were treated with the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF). Of the twelve patients with acute lymphoblastic leukaemia of the thymic phenotype (Thy-ALL), seven went into complete remission after one or two courses of therapy. Two other (Thy-ALL) patients showed good partial response, and three were resistant to dCF. The five patients with acute leukaemia of other phenotypes had progression of disease despite treatment with dCF. Response to dCF can be predicted from the pattern of change in cellular nucleotide levels in blood and/or bone marrow blasts which have been treated in vitro with dCF and deoxyadenosine. The main adverse effects of dCF therapy were renal and liver dysfunction, conjunctivitis, and haemolysis.

Topics: Acute Disease; Adenosine Deaminase; Adolescent; Adult; Child; Child, Preschool; Coformycin; Conjunctivitis; Female; Hemolysis; Humans; Infant; Kidney; Leukemia; Leukemia, Lymphoid; Liver; Male; Pentostatin; Phenotype; Ribonucleosides; T-Lymphocytes

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.

Topics: Adenosine; Adenosine Deaminase Inhibitors; Adenosine Kinase; Adolescent; Adult; Aged; Bronchitis; Coformycin; Coma; Conjunctivitis; Deoxyadenosines; Female; Humans; Kidney Diseases; Leukemia, Lymphoid; Lymphoma; Male; Middle Aged; Mycosis Fungoides; Nucleoside Deaminases; Pentostatin; Phosphotransferases; Phosphotransferases (Alcohol Group Acceptor); Ribonucleosides