title: Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias.
abstract: OBJECTIVE
  The nucleoside analogs fludarabine, 2'-deoxycoformycin (DCF), and 2-chlorodeoxyadenosine (CdA), commonly used in the treatment of patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL), are associated with myelosuppression and profound and prolonged immunosuppression. These complications raise the possibility of an increase in secondary malignancies in patients whose disease already places them at greater risk. The purpose of the present study was to assess the frequency of second tumors in patients with CLL who are treated with fludarabine and in patients with HCL who are treated with DCF and CdA.
  
  
  METHODS
  We reviewed the long-term follow-up data for 2,014 patients treated on National Cancer Institute Group C protocols with fludarabine for relapsed and refractory CLL and with DCF and CdA for HCL using a Second Cancer Report. The numbers of observed and expected secondary tumors were compared.
  
  
  RESULTS
  Median follow-up periods for the DCF (n = 409), fludarabine (n = 724), and CdA (n = 979) studies were 6.9, 7.4, and 5.1 years, respectively. The 111 malignancies were most commonly lymphoma (25 patients), prostate (19), lung (15), colorectal (nine), bladder (six), and breast (six), but also CNS, stomach, ovary, head and neck, melanoma, sarcoma, testicular, and myeloid leukemias. Compared with age-adjusted 1994 Surveillance and Epidemiology End-Results rates for the general population, the observed/expected frequencies for DCF, fludarabine, and CdA were 1.43 (95% confidence interval [CI], 0.93 to 2.10), 1.65 (95% CI, 1.04 to 2.47), and 1.50 (95% CI, 1.14 to 1.93), respectively, indicating a significant (at P =.05) increase in risk for patients treated on the latter two protocols compared with a normal population. However, these values are consistent with the increase already associated with these diseases.
  
  
  CONCLUSIONS
  Despite their immunosuppression, nucleoside analogs can be safely administered to patients with CLL or HCL without a significantly increased risk of secondary malignancies.
authors.affiliation: The Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. chesonb@ctep.nci.nih.gov
authors.forename: B D
authors.initials: BD
authors.lastname: Cheson
authors.forename: D A
authors.initials: DA
authors.lastname: Vena
authors.forename: J
authors.initials: J
authors.lastname: Barrett
authors.forename: B
authors.initials: B
authors.lastname: Freidlin
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017338:Cladribine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology*; D015649:Pentostatin / Q000009:adverse effects / Q000627:therapeutic use*; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D015649:Pentostatin; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine