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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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References

  1. Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336:897–904.

    Article  CAS  Google Scholar 

  2. Bhatia S, Louie AD, Bhatia R, O’Donnell MR, Fung H, Kashyap A, et al. Solid cancers after bone marrow transplantation. J Clin Oncol. 2001;19:464–71.

    Article  CAS  Google Scholar 

  3. Rizzo JD, Curtis RE, Socie G, Sobocinski KA, Gilbert E, Landgren O, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood. 2009;113:1175–83.

    Article  CAS  Google Scholar 

  4. Shimoni A, Shem-Tov N, Chetrit A, Volchek Y, Tallis E, Avigdor A, et al. Secondary malignancies after allogeneic stem-cell transplantation in the era of reduced-intensity conditioning; the incidence is not reduced. Leukemia. 2013;27:829–35.

    Article  CAS  Google Scholar 

  5. Kolb HJ, Socie G, Duell T, Van Lint MT, Tichelli A, Apperley JF, et al. Malignant neoplasms in long-term survivors of bone marrow transplantation. Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group. Ann Intern Med. 1999;131:738–44.

    Article  CAS  Google Scholar 

  6. Tanaka Y, Kurosawa S, Tajima K, Tanaka T, Ito R, Inoue Y, et al. Increased incidence of oral and gastrointestinal secondary cancer after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2017;52:789–91.

    Article  CAS  Google Scholar 

  7. Shimada K, Yokozawa T, Atsuta Y, Kohno A, Maruyama F, Yano K, et al. Solid tumors after hematopoietic stem cell transplantation in Japan: incidence, risk factors and prognosis. Bone Marrow Transplant. 2005;36:115–21.

    Article  CAS  Google Scholar 

  8. Ehrhardt MJ, Brazauskas R, He W, Rizzo JD, Shaw BE. Survival of patients who develop solid tumors following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2016;51:83–88.

    Article  CAS  Google Scholar 

  9. Ringden O, Brazauskas R, Wang Z, Ahmed I, Atsuta Y, Buchbinder D, et al. Second solid cancers after allogeneic hematopoietic cell transplantation using reduced-intensity conditioning. Biol Blood Marrow Transplant. 2014;20:1777–84.

    Article  Google Scholar 

  10. Majhail NS, Brazauskas R, Rizzo JD, Sobecks RM, Wang Z, Horowitz MM, et al. Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood. 2011;117:316–22.

    Article  CAS  Google Scholar 

  11. Abou-Mourad YR, Lau BC, Barnett MJ, Forrest DL, Hogge DE, Nantel SH, et al. Long-term outcome after allo-SCT: close follow-up on a large cohort treated with myeloablative regimens. Bone Marrow Transplant. 2010;45:295–302.

    Article  CAS  Google Scholar 

  12. Baker KS, DeFor TE, Burns LJ, Ramsay NKC, Neglia JP, Robison LL. New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol. 2003;21:1352–8.

    Article  Google Scholar 

  13. Gunnarsson N, Stenke L, Hoglund M, Sandin F, Bjorkholm M, Dreimane A, et al. Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era. Br J Haematol. 2015;169:683–8.

    Article  CAS  Google Scholar 

  14. Gunnarsson N, Hoglund M, Stenke L, Wallberg-Jonsson S, Sandin F, Bjorkholm M, et al. Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia. Leukemia. 2016;30:1562–7.

    Article  CAS  Google Scholar 

  15. Frederiksen H, Farkas DK, Christiansen CF, Hasselbalch HC, Sorensen HT. Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study. Blood. 2011;118:6515–20.

    Article  CAS  Google Scholar 

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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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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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