Second malignancies after treatment of childhood non-Hodgkin lymphoma: a report of the Berlin-Frankfurt-Muenster study group

Haematologica. 2021 May 1;106(5):1390-1400. doi: 10.3324/haematol.2019.244780.


Second malignant neoplasms pose a concern for survivors of childhood cancer. We evaluated incidence, type and risk factors for second malignant neoplasms in patients included in Berlin-Frankfurt-Muenster protocols for childhood non-Hodgkin lymphoma. 3590 patients <15 years of age at diagnosis registered between 01/1981 and 06/2010 were analyzed. Second malignant neoplasms were reported by the treating institutions and the German Childhood Cancer Registry. After median follow-up of 9.4 years (Quartile, Q1 6.7 and Q3 12.1) 95 second malignant neoplasms were registered (26 carcinomas including 9 basal cell carcinomas, 21 acute myeloid leukemias/myelodysplastic syndromes, 20 lymphoid malignancies, 12 CNS-tumors, and 16 other). Cumulative incidence at 20 years was 5.7±0.7%, standard incidence ratio excluding basal cell carcinomas was 19.8 (95% CI 14.5-26.5). Median time from initial diagnosis to second malignancy was 8.7 years (range: 0.2-30.3). Acute-lymphoblastic-leukemia-type therapy, cumulative anthracycline dose, and cranial radiotherapy for brain tumor-development were significant risk factors in univariate analysis only. In multivariate analysis including risk factors significant in univariate analysis, female sex (HR 1.87, 95% CI 1.23-2.86, p=0.004), CNS-involvement (HR 2.24, 95% CI 1.03-4.88, p=0.042), lymphoblastic lymphoma (HR 2.60, 95% CI 1.69-3.97, p<0.001), and cancer-predisposing condition (HR 11.2, 95% CI 5.52-22.75, p<0.001) retained an independent risk. Carcinomas were the most frequent second malignant neoplasms after non-Hodgkin lymphoma in childhood followed by acute myeloid leukemia and lymphoid malignancies. Female sex, lymphoblastic lymphoma, CNS-involvement, or/and known cancer-predisposing condition were risk factors for second malignant neoplasm-development. Our findings set the basis for individualized long-term follow-up and risk assessment of new therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cranial Irradiation
  • Female
  • Humans
  • Incidence
  • Lymphoma, Non-Hodgkin* / diagnosis
  • Lymphoma, Non-Hodgkin* / epidemiology
  • Lymphoma, Non-Hodgkin* / etiology
  • Neoplasms, Second Primary* / diagnosis
  • Neoplasms, Second Primary* / epidemiology
  • Neoplasms, Second Primary* / etiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  • Risk Factors

Grant support

FundingThis study was supported by the Forschungshilfe Station Peiper (Research Support Peiper), Germany, and the Deutsche Kinderkrebsstiftung (German Childhood Cancer Foundation) for the NHL-BFM Registry 2012 (DKS 2014.11 A/B), and the St. Anna Kinderkrebsforschung (Children’s Cancer Research Institute), Austria.