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Br J Haematol. 2019 Apr;185(2):232-239. doi: 10.1111/bjh.15777. Epub 2019 Jan 31.

Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia.

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Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Centre for Primary Health Care Research, Lund University, Malmö, Sweden.
Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Centre for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan.
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Comprehensive Cancer Centre, Helsinki University Hospital, Helsinki, Finland.


Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi-directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (24·58 for in situ and 7·63 for invasive), Merkel cell carcinoma (14·36), Hodgkin lymphoma (7·16) and Kaposi sarcoma (6·76). Conversely, 15 CLL cancer pairs were reciprocally increased. The increased risks were reciprocal for ALL and four cancers. RR for ALL was 15·35 after myeloid neoplasia. HCL showed reciprocally increased RRs with non-Hodgkin lymphoma and melanoma. The concordance between RRs for bi-directional associations between CLL and different cancers, and HCL and different cancers was highly significant. For CLL (also for HCL), the bi-directional risks with skin cancers and other immune-related cancers suggest the probable involvement of immune dysfunction. For ALL, treatment may contribute to risks of multiple SPCs. Increased risk of ALL after haematological neoplasms may indicate bone marrow dysfunction. These findings may help guide treatment decisions and prognostic assessment.


B cell leukaemia; bi-directional risk; immune suppression; mechanistic implication; second cancers


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