Klin Padiatr 2020; 232(02): 88
DOI: 10.1055/s-0040-1701841
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© Georg Thieme Verlag KG Stuttgart · New York

The prognostic value of HLA-G genetic marker in paediatric Hodgkin lymphoma patients enrolled in the italian AIEOP-LH2004 trial

V De Re
1   IRCCS Centro di Riferimento Oncologico, Immunopathology and Cancer Biomarkers/Centro di Riferimento Oncologico, Aviano, Italy
,
L Caggiari
1   IRCCS Centro di Riferimento Oncologico, Immunopathology and Cancer Biomarkers/Centro di Riferimento Oncologico, Aviano, Italy
,
M De Zorzi
1   IRCCS Centro di Riferimento Oncologico, Immunopathology and Cancer Biomarkers/Centro di Riferimento Oncologico, Aviano, Italy
,
O Repetto
1   IRCCS Centro di Riferimento Oncologico, Immunopathology and Cancer Biomarkers/Centro di Riferimento Oncologico, Aviano, Italy
,
C Elia
2   IRCCS Centro di Riferimento Oncologico, Pediatric Radiotherapy Unit, Aviano, Italy
,
F Lovisa
3   University of Padua, Department of Women’s and Children’s Health, University of Padova, Institute of Paediatric Research Fondazione Città della Speranza, Padova, Italy, Padova, Italy
,
L Mussolin
3   University of Padua, Department of Women’s and Children’s Health, University of Padova, Institute of Paediatric Research Fondazione Città della Speranza, Padova, Italy, Padova, Italy
,
E S d’Amore
4   San Bortolo Hospital, Pathology, Vicenza, Italy
,
M Pillon
3   University of Padua, Department of Women’s and Children’s Health, University of Padova, Institute of Paediatric Research Fondazione Città della Speranza, Padova, Italy, Padova, Italy
,
P Muggeo
5   University of Bari, Paediatric Hemato-Oncology, Bari, Italy
,
P Pierani
6   Ospedale G. Salesi, Pediatric Hematology and Oncology, Ancona, Italy
,
R Mura
7   Ospedale Regionale per le Microcitemie, Pediatric Haemato-Oncology, Cagliari, Italy
,
S D’Amico
8   Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele, Pediatric Hematology-Oncology, Catania, Italy
,
P Farruggia
9   A.R.N.A.S. Ospedali Civico Di Cristina e Benfratelli, Pediatric Hematology and Oncology, Palermo, Italy
,
L Vinti
10   IRCCS Ospedale Bambino Gesù, Paediatric Hemato-Oncology, Roma, Italy
,
T Casini
11   Meyer Paediatric Hospital, Paediatric Hemato-Oncology, Florence, Italy
,
A Garaventa
12   IRCCS Istituto Giannina Gaslini, Paediatric Hemato-Oncology and Bone Marrow Transplantation, Genova, Italy
,
K Perruccio
13   Azienda Ospedaliera Universitaria, Ospedale Santa Maria della Misericordia, Paediatric Hemato-Oncology, Perugia, Italy
,
S Bernasconi
14   Azienda Ospedaliera Universitaria Pisana, Paediatric Hemato-Oncology, Pisa, Italy
,
M L Moleti
15   Policlinico Umberto I, Sapienza University, Hematology, Rome, Italy
,
R Burnelli
16   Azienda Ospedaliera Universitaria, Ospedale Sant’Anna, Pediatric Hematology-Oncology, Ferrara, Italy
,
M Mascarin
2   IRCCS Centro di Riferimento Oncologico, Pediatric Radiotherapy Unit, Aviano, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
18 March 2020 (online)

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Introduction We found HLA-G+3027 single nucleotide polymorphism (SNP) as a potential negative prognostic marker in pediatric Hodgkin lymphoma (HL) patients treated according to LH-2004 protocol[1]. However, its association with poor outcome could be validated. Our aim was to support the role of HLA-G+3027 in LH-2004 long term study and in association with hematochemical markers.

Methods The study included 104 HL patients, age range 3 to 18 years (y), who received LH2004 treatment. We identify 28 relapsed/progressive patients (26.9%), with a mean time of event 1.45 y ±SD1.14. Median follow up 5.16 y ±SD3.96. Analyses were conducted on even free survival (EFS) and overall survival (OS) based on the therapeutic risk groups (TG), histological classification, gender, HLA-G+3027 SNP, and hematochemical test (VES, albumin, ferritin, Hb, WBC, neutrophils, eosinophils, basophils, lymphocytes, monocytes, LUC, platelets) values at the time of diagnosis[2].

Results The mean age of the patients was 13.08 y ±0.32, 37.5% were female. Groups of algorithm (GR) combining HLA-G+3027 with TG (Y=-3.94+1.36 C/A+0.94 TG) was able to better identify patients with an inferior EFS (mean time at relapse/progression 7.69y ±SE1.76, 12.70y ± SE1.05, 14.5y ±SE0.50, for GR3, GR2, GR1, respectively, p=0.0073) than GT alone (12.63±SE1.0, 10.99y±SE0, 13.46y ±SE1.03 for TG3, TG2 and TG1, respectively p=0.015). The cutoff value of GR was found as >-2.06, p=0.0013. The decrease lymphocyte value at the time of diagnosis was significantly related to the algorithm, r -0.475, p<0.0001 and with poor prognosis (EFS r=0.39, p=0.0389). Multivariate analysis for OS revealed mixed-cellularity histological subtype and increased platelets value as two worse independent factors (stepwise, p=0.029).

Conclusion Our findings show that including HLA-G+3027 SNP value in the TG score increases the prognostic EFS significance in a long follow-up of LH-2004 trial. An indication of an association between the lower number of lymphocyte cells at diagnosis and the GR with EFS was seen. Both histological classification and platelets counts were independent factors associated with OS.


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  • References

  • 1 De Re V, Caggiari L. , et al. 2017. , HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin’s lymphoma. , Oncotarget . , 105957-70
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  • References

  • 1 De Re V, Caggiari L. , et al. 2017. , HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin’s lymphoma. , Oncotarget . , 105957-70
    Google Scholar
  • 2 Farruggia P, Puccio G. , et al. 2016; , The prognostic value of biological markers in paediatric Hodgkin lymphoma. Eur J Cancer Oxf Engl. 1990, 52: 33-40
    PubMedGoogle Scholar