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Non-Hodgkin lymphoma in pediatric patients with common variable immunodeficiency

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Abstract

Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency associated with an increased risk of malignancy in adulthood, with lymphoma as one of the major causes of death. The aim of this study is to describe those malignancies detected in our cohort of pediatric CVID patients. We reviewed the clinical and laboratory data and the treatments and their outcomes in all pediatric CVID patients from our institution that developed a neoplasia. Four malignancies were diagnosed in three out of 27 pediatric CVID patients. Three malignancies were non-Hodgkin lymphoma (NHL) of B cell origin (mean age at diagnosis: 8 years old), and the remaining was a low-grade astrocytoma. Among NHL, two were mucosa-associated lymphoid tissue (MALT) lymphomas and one was associated with Epstein-Barr virus infection. NHL developed before CVID diagnosis in two patients. CVID patients showed different clinical phenotypes and belonged to different groups according Euroclass and Pediatric classification criteria.

Conclusions: Malignancies, especially lymphoma, may develop in pediatric CVID patients with no previous signs of lymphoid hyperplasia and even before CVID diagnosis. Consequently, strategies for cancer prevention and/or early diagnosis are required in pediatric CVID patients.

What is Known:

• Non-Hodgkin lymphomas are the most frequent neoplasm reported in pediatric CVID patients.

• “Polyclonal lymphoproliferation” clinical phenotype is associated with increased risk of lymphoid malignancy and group smB-Tr hi of the Euroclass classification with an increased risk of lymphadenopathy.

What is New:

• We report a higher incidence of non-Hodgkin lymphomas compared to previous publications in pediatric patients, and our patients are younger than reported.

• None of our patients belongs to “polyclonal lymphoproliferation” clinical phenotype, and a common B cell subphenotyping (smB+21 lo ) was identified in two of lo the three patients.

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Abbreviations

APRIL:

A proliferation-inducing ligand

BAFF:

B cell activating factor

CHOP:

Cyclophosphamide, doxorubicin, vincristine, prednisone

CMV:

Cytomegalovirus

COPADM:

Cyclophosphamide, vincristine, prednisolone, doxorubicine, methotrexate chemotherapy

CSF:

Cerebrospinal fluid

CT:

Computed tomography

CVID:

Common variable immunodeficiency

CYVE:

Cytarabine, etoposide

FDG-PET:

18-Fluoro-deoxyglucose positron emission tomography

EBV:

Epstein-Barr virus

HHV8:

Human herpes virus 8

IgA:

Immunoglobulin A

IgG:

Immunoglobulin G

IgM:

Immunoglobulin M

IRT:

Immunoglobulin replacement therapy

LMB:

B cell non-Hodgkin lymphoma and Burkitt lymphoma/leukemia

MALT:

Mucosa-associated lymphoid tissue

NHL:

Non-Hodgkin lymphomas

PCR:

Polymerase chain reaction

qRT-PCR:

Reverse transcriptase PCR

SIR:

Standardized incidence ratio

WHO:

World Health Organization

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Acknowledgments

The authors would like to thank our patients and their families for their confidence and the multidisciplinary team involved in the care of these patients. We gratefully acknowledge Ferran Casals for the genetic analyses supported by SAF2012-35025 grant from the Spanish Ministerio de Economía y Competitividad.

Conflict of interest

The authors declare that they have no conflict of interest.

Author’s contributions

M.P.G. was involved in clinical monitoring of patients, acquisition and interpretation of data and drafting of the manuscript; L.A. in data analysis and revision of the manuscript; MT.G.M. in clinical monitoring of patients and preparation of figure and table; O.C.M. contributed with clinical monitoring of patients and critical revision of the manuscript; K.R.E., O.D. and AM.P.M. with collection and analysis of data; JI.A. and G.V. made genomic DNA sequencing and analysis; M.J.O. developed and analyzed in vitro assays and phenotyping, being also responsible along with MA.M.M. of coordination and supervision of research work and data analysis, and critical revision of the manuscript; in general all the authors discussed and revised the manuscript.

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Authors and Affiliations

  1. Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu-Universitat de Barcelona, Passeig Sant Joan de Déu, 2, 08950, Esplugues de Llobregat, Barcelona, Spain

    Monica Piquer Gibert, Laia Alsina, María Teresa Giner Muñoz, Karen Ruiz Echevarria, Olga Dominguez, Ana María Plaza Martín & Maria Anunciacion Martin-Mateos

  2. Oncology Pediatric Department, Hospital Sant Joan de Déu-Universitat de Barcelona, Passeig Sant Joan de Déu, 2, 08950, Esplugues de Llobregat, Barcelona, Spain

    Ofelia Cruz Martínez

  3. Immunology Department–CDB, Hospital Clinic-IDIBAPS, Calle Villarroel, 170, 08036, Barcelona, Spain

    Juan I. Arostegui & Manel Juan Otero

  4. Functional Unit of Immunology, Hospital Sant Joan de Déu-Hospital Clinic, Barcelona, Spain

    Monica Piquer Gibert, Laia Alsina, María Teresa Giner Muñoz, Olga Dominguez, Ana María Plaza Martín, Juan I. Arostegui, Manel Juan Otero & Maria Anunciacion Martin-Mateos

  5. IBE-Institute of Evolutionary Biology (UPF-CSIC), Universitat Pompeu Fabra, Barcelona, Catalonia, Spain

    Guillem de Valles

Authors
  1. Monica Piquer Gibert
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  2. Laia Alsina
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  3. María Teresa Giner Muñoz
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  4. Ofelia Cruz Martínez
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  5. Karen Ruiz Echevarria
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  6. Olga Dominguez
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  7. Ana María Plaza Martín
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  8. Juan I. Arostegui
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  9. Guillem de Valles
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  10. Manel Juan Otero
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  11. Maria Anunciacion Martin-Mateos
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Corresponding author

Correspondence to Monica Piquer Gibert.

Additional information

Communicated by David Nadal

Manel Juan Otero and Maria Anunciacion Martin-Mateos share senior co-authorship.

Revisions received: 05 December 2014 / 03 February 2015

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Piquer Gibert, M., Alsina, L., Giner Muñoz, M.T. et al. Non-Hodgkin lymphoma in pediatric patients with common variable immunodeficiency. Eur J Pediatr 174, 1069–1076 (2015). https://doi.org/10.1007/s00431-015-2508-6

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  • DOI: https://doi.org/10.1007/s00431-015-2508-6

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