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Incidence and risk factors of secondary cancers after allogeneic stem cell transplantation: analysis of a single centre cohort with a long follow-up

Bone Marrow Transplantation volume 54, pages 334–337 (2019)Cite this article

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As the long-term outcome of allogeneic stem cell transplantation (allo-SCT) has improved, the significance of post-transplant late effects is growing. In long-term survivors, secondary solid cancers have been reported to appear at least at twice the rate expected in the general population [1,2,3,4]. The reported cumulative incidence of secondary cancers varies from 1 to 11% at 10 years and from 2−12% at 15 years [1, 5, 6]. The 5-year overall survival (OS) rate from the diagnosis of a secondary malignancy is 42−50%, but the prognosis varies according to the type of the cancer [7, 8]. Risk factors for secondary cancers include the use of total body irradiation (TBI), the intensity of the conditioning regimen, chronic GvHD (cGvHD), and the age at transplantation, but the data are conflicting [1, 4, 6, 9]

We investigated the incidence, the subtypes, and the risk factors of secondary cancers in patients aged over 16 who underwent allo-SCT in Helsinki University Hospital between January 1996 and December 2014. Patients with haploidentical donors, cord blood grafts, or double allo-SCT (34 in total) were excluded. Cyclosporine A and methotrexate were used as GvHD prophylaxis. We included all secondary malignancies, except for post-transplant lymphoproliferation and non-melanoma skin cancers. The follow-up of the living patients was to the end of May 2017. The patient data were collected from the EBMT Promise database. The incidence rates of specific cancer types in Finland were obtained from the Finnish Cancer Registry, which maintains a database on cancers detected in Finland (population 5.5 million). Descriptive cross-tabulations were created between the response variable (incidence of secondary malignancy) and the predefined potential risk factors (age at transplantation, gender, diagnosis, conditioning intensity, TBI, anti-thymocyte globulin as a part of the conditioning, graft type, donor type, acute GvHD (aGvHD), aGvHD ≥ gr 2, cGvHD, and extensive cGvHD). The effect of the risk factors was first analysed with univariate logistic regression. Second, a multivariate logistic regression model was fitted, where the variables found meaningful (P value < 0.1) in the univariate analysis were inserted into the model as fixed terms. As both cGvHD (any grade) and extensive cGvHD were significant in the univariate analysis, only the one (cGvHD any grade) with the lower P value was included in the multivariate model. Odds ratios (OR) and their 95% CIs were used to quantify the results of the logistic regression models. The ORs are constructed for the probability for the secondary cancer to occur. The cumulative incidence of secondary cancers and OS were estimated by the Kaplan-Meier method where death or the end of the follow-up time were competitive events, whichever came first. The incidence rates of secondary cancers were evaluated by calculating the incidence rate per 100 000 person-years applying a formula: (number of events/sum of follow-up times in years of the sample population)*100 000. This approach was taken to be able to compare with rates from the Finnish Cancer Registry. The CIs for the incidence rates /100 000 person-years were calculated using a Poisson regression model. Standardised incidence ratios (SIR) of secondary cancers were calculated as the ratio of the observed incidence rates to the expected population incidence rates. P values of < 0.05 were considered statistically significant, all the presented P values are two-tailed. Statistical analyses were carried out with SAS® for Windows (version 9.3; SAS Institute, Cary, NC, USA).

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Acknowledgements

We thank EBMT registry co-ordinator Mrs. Marja Pekkanen for the data collection. This study was supported by the Blood Diseases Research Foundation, Helsinki, Finland.

This study is compliant with the ethical standards of the Declaration of Helsinki.

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  1. Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center and Helsinki University, Helsinki, Finland

    Eeva Martelin, Liisa Volin, Maija Itälä-Remes, Riitta Niittyvuopio, Vesa Lindström, Jouni Heiskanen, Tapani Ruutu & Anne Nihtinen

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  1. Eeva Martelin
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Martelin, E., Volin, L., Itälä-Remes, M. et al. Incidence and risk factors of secondary cancers after allogeneic stem cell transplantation: analysis of a single centre cohort with a long follow-up. Bone Marrow Transplant 54, 334–337 (2019). https://doi.org/10.1038/s41409-018-0290-6

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