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Primary immunodeficiencies and their associated risk of malignancies in children: an overview

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Abstract

Primary immunodeficiency disorders represent a heterogeneous spectrum of diseases, predisposing to recurrent infections, allergy, and autoimmunity. While an association between primary immunodeficiency disorders and increased risk of cancer has been suggested since the 1970s, renewed attention has been given to this topic in the last decade, largely in light of the availability of large registries as well as advances in next generation sequencing. In this narrative review, we will give an insight of the primary immunodeficiencies that are commonly responsible for the greater number of cancers in the primary immunodeficiency disorders population. We will describe clinical presentations, underlying genetic lesions (if known), molecular mechanisms for carcinogenesis, as well as some management considerations. We will also comment on the future directions and challenges related to this topic.

Conclusion: The awareness of the association between several primary immunodeficiencies and cancer is crucial to provide the best care for these patients.

What is Known:

• Patients with primary immunodeficiency have an increased risk of malignancy. The type of malignancy is highly dependent on the specific primary immunodeficiency disorder.

What is New:

• Survival in patients with primary immunodeficiency disorders has been improving, and conversely also their lifetime risk of malignancy.

• International collaboration and multinational registries are needed to improve our knowledge and therapeutic strategies.

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Abbreviations

PID:

Primary immunodeficiency disorders

AT:

Ataxia telangiectasia

UV:

Ultraviolet

NHL:

Non-Hodgkin lymphoma

BS:

Bloom syndrome

AML:

Acute myeloid leukemia

ALL:

Acute lymphoblastic leukemia

NBS:

Nijmegen breakage syndrome

CVID:

Common variable immunodeficiency

ALPS:

Autoimmune lymphoproliferative syndrome

MDS:

Myelodysplastic syndrome

WAS:

Wiskott–Aldrich syndrome

HSCT:

Hematopoietic stem cell transplantation

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Author notes

  1. Samuele Renzi and Karin Petra Sabine Langenberg-Ververgaert contributed equally to this work.

Authors and Affiliations

  1. Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada

    Samuele Renzi, Nicolas Waespe, Salah Ali, Jack Bartram, Orli Michaeli & Michaela Cada

  2. University of Toronto, Toronto, Ontario, Canada

    Samuele Renzi, Salah Ali, Orli Michaeli, Julia Upton & Michaela Cada

  3. Department of Translational Research, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

    Karin Petra Sabine Langenberg-Ververgaert

  4. Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

    Nicolas Waespe

  5. CANSEARCH Research Laboratory, Department of Pediatrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Nicolas Waespe

  6. Department of Haematology, Great Ormond Street Hospital for Children, London, UK

    Jack Bartram

  7. Division of Immunology, The Hospital for Sick Children, Toronto, Ontario, Canada

    Julia Upton

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SR and KPS conceived this article, reviewed the literature and co-wrote the manuscript. NW, SA, JB and OM reviewed the literature and co-wrote the manuscript. JU and MC co-wrote the manuscript and critically reviewed it.

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Correspondence to Samuele Renzi.

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Renzi, S., Langenberg-Ververgaert, K.P.S., Waespe, N. et al. Primary immunodeficiencies and their associated risk of malignancies in children: an overview. Eur J Pediatr 179, 689–697 (2020). https://doi.org/10.1007/s00431-020-03619-2

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