Abstract 1559

Poster Board I-582

Introduction

Median age of Hodgkin's Lymphoma (HL) cases in children is 12-14 years. Epidemiological and histological features are similar to HL occurring in young adults. In contrast, HL under the age of 10 has specific features; it predominates strongly in boys and it is more frequently associated with Epstein-Barr virus (EBV). There is accumulating evidence for an inherited susceptibility to HL based on many reports of familial aggregation of the disease in adults and in childhood. Cohort studies have shown that patients affected by several immune deficiency syndromes - e.g. X-linked lymphoproliferative syndrome (XLP), functional deficit of Fas/FasL pathway and common variable immuno-deficiency (CVID) - are risk factors of HL. They are currently thought to explain only few cases of HL. However, their frequency may be underestimated since, to our knowledge, no study has systematically looked for these disorders among patients with HL.

Methods

We intend to search for qualitative and quantitative immune deficiencies as susceptibility factors to child's HL in a prospective study related to Euronet –PHL C1 protocol. Patients and their parents are invited to participate to the present study at inclusion time. Lymphocyte sub-populations are analysed by flow cytometry using various panels of monoclonal antibodies directed against the following markers: CD45, CD3, CD4, CD8, TCRαβ, TCRγΔ, CD19, CD5, kappa, lambda, CD27, IgM, IgD, CD21, CD38, CD16, CD57 and CD56-CD16. Immune study is completed by immunoglobulin and IgG subclasses quantification and anti-tetanus serology.

Results

Sixty patients at diagnosis of HL have been analysed. Median age of the study population is 13 years, (5-18 years). Gender-ratio M/F is 1.1. It increases to 6 below the age of 10. An unexpected high frequency of B-cell lymphopenia has been detected in 20 out of 60 patients (33.3%) (median 68 cells/μl, range 19-90) (Table 1). Immunoglobulin and anti-tetanus IgG levels are normal in all these cases. T-cell lymphopenia is observed in a low proportion of cases (3/60 (5%), HIV infected patients being excluded) (Table 1). These B and T-cell quantitative abnormalities do not correlate with age or gender. In contrast to the high frequency of quantitative defects, we have not detected any qualitative defect of specific B- or T-cell subpopulations. Moreover, the analyses of 26 parents of the lymphopenic patients has not shown any decreased lymphocytic population. Finally, our analyses exclude XLP, functional deficit of Fas/FasL pathway and CVID in all cases.

Discussion

The present detailed immune analysis of 60 children diagnosed with HL has not detected any characteristic immune deficiency syndrome confirming their low prevalence among children with HL. However, we have found a high frequency of B-cell global lymphopenia. Two studies had previously reported severe B-cell lymphopenia in patients with HL. The pathophysiological mechanisms leading to lymphopenia remain largely unknown. Since we did not find any qualitative immune defect – in B-cell subpopulation or in serological immune analysis - nor any defect among the parents we analysed, we propose that this peripheral blood lymphopenia is likely to be due to lymphocyte trafficking and homing rather than due to an absolute quantitative deficiency.

Table 1

Characteristics of the children with Hodgkin's Lymphoma and low B- or T-cell counts

PatientAgeGenderB-cells (106/L)(NV: 100-500)T-cells (106/L)(NV: 600-2400)IgM (g/L)(NV: 0.4-2.3)IgG (g/L)(NV: 7-16)IgA (g/L)(NV: 0.7-4.0)
1 16 F 53 1740 2.2 13.1 2.0 
2 12 F 90 546 2.2 14.2 1.9 
3 15 M 64 916 1.7 9.8 1.0 
4 15 F 56 406 0.6 13.9 1.8 
5 16 M 88 720 0.4 10.2 1.1 
6 14 F 82 986 2.3 11.5 3.0 
7 18 M 80 489 0.7 16.4 2.4 
8 17 M 79 744 0.5 8.2 0.6 
9 10 M 48 783 1.9 20.5 2.8 
10 17 M 58 718 0.8 11.9 2.2 
11 15 M 77 522 0.6 6.1 1.0 
12 17 M 90 454 1.5 13.8 2.6 
13 17 M 34 480 1.5 8.6 1.5 
14 13 M 19 744 1.5 21.7 5.9 
15 14 F 92 671 1.4 9.4 1.8 
16 14 F 71 857 1.5 18.1 4.1 
17 12 M 85 1651 1.0 10.7 2.0 
18 7 M 71 1475 1.7 18.9 2.5 
19 16 F 82 349 1.2 14.9 2.9 
20 18 M 38 527 1.6 13.4 2.7 
21 16 M 115 379 0.9 13.9 1.3 
22 16 M 105 354 0.5 11.3 3.1 
PatientAgeGenderB-cells (106/L)(NV: 100-500)T-cells (106/L)(NV: 600-2400)IgM (g/L)(NV: 0.4-2.3)IgG (g/L)(NV: 7-16)IgA (g/L)(NV: 0.7-4.0)
1 16 F 53 1740 2.2 13.1 2.0 
2 12 F 90 546 2.2 14.2 1.9 
3 15 M 64 916 1.7 9.8 1.0 
4 15 F 56 406 0.6 13.9 1.8 
5 16 M 88 720 0.4 10.2 1.1 
6 14 F 82 986 2.3 11.5 3.0 
7 18 M 80 489 0.7 16.4 2.4 
8 17 M 79 744 0.5 8.2 0.6 
9 10 M 48 783 1.9 20.5 2.8 
10 17 M 58 718 0.8 11.9 2.2 
11 15 M 77 522 0.6 6.1 1.0 
12 17 M 90 454 1.5 13.8 2.6 
13 17 M 34 480 1.5 8.6 1.5 
14 13 M 19 744 1.5 21.7 5.9 
15 14 F 92 671 1.4 9.4 1.8 
16 14 F 71 857 1.5 18.1 4.1 
17 12 M 85 1651 1.0 10.7 2.0 
18 7 M 71 1475 1.7 18.9 2.5 
19 16 F 82 349 1.2 14.9 2.9 
20 18 M 38 527 1.6 13.4 2.7 
21 16 M 115 379 0.9 13.9 1.3 
22 16 M 105 354 0.5 11.3 3.1 
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Disclosures

No relevant conflicts of interest to declare.

Topics:
child, deficiency, immune, hodgkin's disease, genetic predisposition to disease, lymphopenia, immunoglobulin g, antigens, cd16, common variable hypogammaglobulinemia, immunoglobulin m, immunoglobulins

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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