Risk of second malignant neoplasms after cyclophosphamide-based chemotherapy with or without radiotherapy for non-Hodgkin lymphoma

Leuk Lymphoma. 2013 Jul;54(7):1396-404. doi: 10.3109/10428194.2012.743657. Epub 2012 Nov 26.


Relatively little information is available on quantitative risks of therapy-induced second malignant neoplasm (SMN) in patients with non-Hodgkin lymphoma (NHL). A nested case-control study was conducted in a cohort of 3412 patients treated for NHL between 1990 and 2006, including 118 patients with SMN and 472 controls. Risks of leukemia/lung/breast/colorectal and bladder cancer were higher in NHL compared with the general population. A higher risk of leukemia was restricted to patients given a cumulative dose of cyclophosphamide more than 11 250 mg/m(2). However, no significant association was found between SMN risk with rituximab, fludarabine, anthracyclines, epipodophyllotoxins and platinum, respectively. In combined modality treatment, involved-field radiation therapy (IFRT) had a higher risk for second solid cancers as compared to involved-nodal radiation therapy (INRT). For patients receiving radiation doses exceeding 40 Gy, the risk of lung cancer and breast cancer was increased. In conclusion, we found that cyclophosphamide-based therapy increased the risk of SMN in NHL. Leukemia risk was linked with high-dose cyclophosphamide. A received larger radiation field or higher radiation dose also could be an important risk factor for the development of SMN.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Lymphoma, Non-Hodgkin / diagnosis
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / radiotherapy
  • Male
  • Middle Aged
  • Neoplasms, Second Primary / epidemiology*
  • Neoplasms, Second Primary / etiology*
  • Radiotherapy / adverse effects*
  • Radiotherapy Dosage
  • Risk*
  • Young Adult


  • Cyclophosphamide