Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study

Leukemia. 2019 Aug;33(8):1996-2005. doi: 10.1038/s41375-019-0487-8. Epub 2019 May 29.


We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00-14.01), ruxolitinib (OR = 3.87, 95% CI 1.18-12.75), and for drug combination (OR = 3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Case-Control Studies
  • Humans
  • Hydroxyurea / adverse effects
  • Neoplasms, Second Primary / chemically induced*
  • Philadelphia Chromosome*
  • Pipobroman / adverse effects
  • Polycythemia Vera / drug therapy*
  • Polycythemia Vera / genetics
  • Primary Myelofibrosis / drug therapy*
  • Pyrazoles / adverse effects
  • Thrombocythemia, Essential / drug therapy*
  • Thrombocythemia, Essential / genetics


  • Antineoplastic Agents
  • INCB018424
  • Pyrazoles
  • Pipobroman
  • Hydroxyurea