pentostatin and Hemolysis

Topics: Blood Proteins; Blood Viscosity; Coformycin; Female; Hemoglobins; Hemolysis; Humans; Immunoglobulin M; Immunoglobulins; Middle Aged; Paraproteins; Pentostatin; Platelet Count; Ribonucleosides; Waldenstrom Macroglobulinemia

2'-Deoxycoformycin (dCF), a tight-binding inhibitor of adenosine deaminase, has recently been entered into clinical trials. Toxicity has included lymphopenia, seizures, coma, conjunctivitis, renal failure, and hemolysis. Mice treated with dCF on a variety of schedules exhibited massive hemolysis. Hemolysis was brief, lasting about 20 hours, and did not recur upon readministration of the drug unless readministration was delayed for at least 6 days after initial exposure, which suggests that a sensitive subpopulation of cells was selectively destroyed. Splenectomy failed to protect the animals from dCF-induced hemolysis. Administration of adenosine or 2'-deoxyadenosine without dCF did not cause hemolysis, and use of these two agents with dCF did not potentiate the observed hemolysis. ATP and dATP levels were measured in erythrocytes, and changes in levels of these nucleotides did not correspond with the development of hemolysis.

Topics: Animals; Coformycin; Dose-Response Relationship, Drug; Drug Evaluation; Erythrocytes; Female; Hematocrit; Hemoglobinuria; Hemolysis; Male; Mice; Mice, Inbred BALB C; Nucleotides; Pentostatin; Ribonucleosides; Splenectomy

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

Topics: Adenosine Deaminase Inhibitors; Adenosine Triphosphate; Animals; Coformycin; Deoxyadenosines; Erythrocytes; Female; Hemolysis; Mice; Mice, Inbred ICR; Nucleoside Deaminases; Pentostatin; Ribonucleosides