Response to 2-chlorodeoxyadenosine in patients with B-cell chronic lymphocytic leukemia resistant to fludarabine

N Engl J Med. 1992 Oct 8;327(15):1056-61. doi: 10.1056/NEJM199210083271504.

Abstract

Background: Patients with untreated B-cell chronic lymphocytic leukemia have a high rate of complete remission when given the halogenated nucleoside analogue fludarabine. However, patients in whom the disease has proved refractory to primary treatment have a reduced life expectancy and a dismal outcome.

Methods: We treated four consecutive patients who had unsatisfactory responses to second-line or subsequent treatment with fludarabine with another halogenated nucleoside analogue, 2-chlorodeoxyadenosine.

Results: One patient with progressing lymphocytosis, anemia, and thrombocytopenia despite 10 courses of fludarabine entered a complete remission when treated with 2-chlorodeoxyadenosine. Two patients who had less-than-partial remissions after six courses of fludarabine had good partial remissions when treated with 2-chlorodeoxyadenosine. One patient with Coombs-positive hemolytic anemia who had no response to three courses of fludarabine had a partial remission, with resolution of hypogammaglobulinemia, when treated with 2-chlorodeoxyadenosine.

Conclusions: There was no evidence of cross-resistance between fludarabine and 2-chlorodeoxyadenosine despite their similar structures. 2-Chlorodeoxyadenosine may induce a complete remission in chronic lymphocytic leukemia that is highly resistant to chemotherapy, and it deserves wider clinical evaluation in patients with this condition.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Chloroadenosine / analogs & derivatives*
  • 2-Chloroadenosine / therapeutic use
  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Cladribine
  • Deoxyadenosines / therapeutic use*
  • Drug Resistance
  • Female
  • Haptoglobins / analysis
  • Humans
  • Immunoglobulins / analysis
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukocyte Count
  • Lymphocytes
  • Male
  • Middle Aged
  • Remission Induction
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use

Substances

  • Antineoplastic Agents
  • Deoxyadenosines
  • Haptoglobins
  • Immunoglobulins
  • 2-Chloroadenosine
  • Cladribine
  • Vidarabine
  • fludarabine