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Secondary malignancies and survival outcomes after autologous stem cell transplantation for follicular lymphoma in the pre-rituximab and rituximab eras: a long-term follow-up analysis from the Spanish GELTAMO registry

Bone Marrow Transplantation volume 53, pages 780–783 (2018)Cite this article

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High-dose therapy supported by autologous stem cell transplantation (HDT/ASCT) is frequently utilized in follicular lymphoma (FL) patients and has contributed to modifying the natural history of the disease [1, 2]. However, a key concern following HDT/ASCT is the occurrence of secondary malignancies. The reported incidence varies between studies, in part due to cohort differences in terms of age, pre-ASCT treatment, use of total body irradiation (TBI)-based conditioning regimens, or length of follow-up, rather than due to differences in the procedure itself [3,4,5,6,7,8,9]. The risk of secondary malignancies following HDT/ASCT in patients with non-Hodgkin lymphoma (NHL) has been specifically described in some papers [3,4,5, 7, 8], with reported 10-year cumulative incidences ranging from 5 to 21% and a 1.6-fold to 3.3-fold greater risk of secondary malignancies compared to the general population. This is primarily driven by the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), which is higher in NHL patients receiving HDT/ASCT compared to those treated with conventional therapy; by contrast, an increased risk of solid malignancies has been demonstrated only in some studies but not others [4, 7, 8, 10]. Nevertheless, the incidence of secondary malignancies following non-transplantation therapy is also higher among patients with NHL than in the general population [11,12,13]. Thus, it is not clear whether the increased risk seen in FL patients undergoing HDT/ASCT is associated explicitly with the ASCT procedure, or whether it is related to chemotherapy and radiotherapy exposure before and after transplantation, or to the disease itself. Additionally, overall survival (OS) among FL patients who develop secondary malignancies is not well characterized.

We retrospectively analyzed a large cohort of 655 FL patients in the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) database who underwent HDT/ASCT over an 18-year period between 1989 and 2007 [14]. Additionally, we assessed the risk of malignancies in the general population using the International Agency for Research on Cancer GLOBOCAN database (year 2012), which includes aggregated data from 12 Spanish cancer registries (covering 21% of the population) for the period 2006–2007 [15] (http://globocan.iarc.fr/Default.aspx). We determined the standardized incidence ratio (SIR; ratio of observed to expected malignancies) for the FL patient population by dividing the number of observed secondary malignancies with the number of expected cases in an age- and sex-matched cohort in the general population. Non-melanoma skin cancers (NMSC) were excluded from SIR analyses because these events are not collected in the GLOBOCAN database. The study cohort had a cumulative follow-up of 7578 patient-years.

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Acknowledgements

The authors would like to acknowledge the patients and their families, all participating members of the GELTAMO study group, Angel Cedillo for administrative support, David Lora for statistical review, and Steve Hill of FireKite, an Ashfield Company, part of UDG Healthcare plc, for editorial assistance in the English language, which was funded by the Foundation Research Institute at the Hospital Universitario 12 de Octubre, and complied with Good Publication Practice 3 ethical guidelines (Battisti et al., Ann Intern Med 2015;163:461–4).

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Authors and Affiliations

  1. Hospital Universitario 12 de Octubre, Madrid, Spain

    Ana Jiménez-Ubieto, Carlos Grande, Pilar Martínez-Sánchez & Juan José Lahuerta

  2. Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain

    Dolores Caballero & Alejandro Martín

  3. Hospital Universitario Marqués de Valdecilla, Santander, Spain

    Lucrecia Yáñez

  4. Hospital Universitario de Canarias, Tenerife, Spain

    Miguel Teodoro Hernández-Garcia

  5. Hospital Universitario Sant Pau, Barcelona, Spain

    Silvana Novelli

  6. Hospital Universitario La Princesa, Madrid, Spain

    Reyes Arranz

  7. Hospital Universitario Donostia-Aránzazu, San Sebastián, Spain

    José Javier Ferreiro

  8. Hospital Universitario Vall de Hebrón, Barcelona, Spain

    Sabella Bobillo

  9. Hospital Universitario de Bellvitge, l’Hospitalet de Llobregat, Barcelona, Spain

    Santiago Mercadal

  10. Hospital Universitario A Coruña, A Coruña, Spain

    Andrea Galeo

  11. Hospital Universitario Ramón y Cajal, Madrid, Spain

    Javier López Jiménez

  12. Hospital Universitario Virgen de la Arriaxaca, Murcia, Spain

    José María Moraleda

  13. Hospital Central de Asturias, Asturias, Spain

    Carlos Vallejo

  14. Hospital Universitario de Vigo, Vigo, Spain

    Carmen Albo

  15. Hospital Universitario Morales de Messeguer, Murcia, Spain

    Elena Pérez

  16. Hospital Universitario Nuestra Señora de La Candelaria, Tenerife, Spain

    Carmen Marrero

  17. Hospital Clinic de Barcelona, Barcelona, Spain

    Laura Magnano & Armando López-Guillermo

  18. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

    Luis Palomera

  19. Hospital Universitario la Fe, Valencia, Spain

    Isidro Jarque

  20. Hospital Clínico San Carlos, Madrid, Spain

    Erika Coria

  21. Hospital del Mar, Barcelona, Spain

    Antonio Salar

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  1. Ana Jiménez-Ubieto
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on behalf of the GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) Cooperative Study Group.

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Correspondence to Ana Jiménez-Ubieto.

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Jiménez-Ubieto, A., Grande, C., Caballero, D. et al. Secondary malignancies and survival outcomes after autologous stem cell transplantation for follicular lymphoma in the pre-rituximab and rituximab eras: a long-term follow-up analysis from the Spanish GELTAMO registry. Bone Marrow Transplant 53, 780–783 (2018). https://doi.org/10.1038/s41409-018-0096-6

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