Risk factors for development of a second lymphoid malignancy in patients with chronic lymphocytic leukaemia

Br J Haematol. 2007 Nov;139(3):398-404. doi: 10.1111/j.1365-2141.2007.06801.x.


Previous studies suggested that patients with chronic lymphocytic leukaemia (CLL) are at a three- to fivefold increased risk of developing a second lymphoproliferative disorder (LPD). This observational cohort study used the Mayo Clinic CLL Database to identify factors associated with developing a second LPD. A second LPD was identified in 26 (2.7%) of 962 CLL patients during a median follow-up of 3.3 years. Diffuse large B-cell lymphoma was the most common subtype of secondary LPD (12 of 26 cases). Patients previously treated for CLL had a trend toward higher prevalence of second LPD (4%) compared with previously untreated patients (2%; P = 0.053). More strikingly, patients treated with purine nucleoside analogues (PNA) had a significantly increased risk of subsequent second LPD (5.2%) compared with patients who had not received PNA (1.9%; P = 0.008). No statistically significant association was observed between risk of second LPD and other CLL characteristics (ZAP-70, CD38, IgV(H) mutation status or cytogenetic abnormalities). In this series, prior treatments with PNA or anthracyclines were the only significant factors associated with risk of developing a second LPD in patients with CLL. Physicians should strictly adhere to established criteria to initiate treatment for CLL patients who are not participating in clinical trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Lymphoma / chemically induced
  • Lymphoma / etiology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Second Primary / chemically induced
  • Neoplasms, Second Primary / etiology*
  • Prognosis
  • Purine Nucleotides / adverse effects
  • Risk Factors
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives


  • Antineoplastic Agents
  • Purine Nucleotides
  • Vidarabine
  • fludarabine