Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis
2
Issued Date
2023-10-01
Resource Type
eISSN
15928721
Scopus ID
2-s2.0-85166518758
Pubmed ID
37051767
Journal Title
Haematologica
Volume
108
Issue
10
Start Page
2743
End Page
2752
Rights Holder(s)
SCOPUS
Bibliographic Citation
Haematologica Vol.108 No.10 (2023) , 2743-2752
Suggested Citation
Moonla C., Polprasert C., Komvilaisak P., Rattanathammethee T., Kongkiatkamon S., Wudhikarn K., Kobbuaklee S., Boonyabaramee P., Tangcheewinsirikul N., Pakakasama S., Rujkijyanont P., Choed-Amphai C., Phuakpet K., Pongudom S., Bunworasate U., Sukswai N., Sosothikul D., Rojnuckarin P. Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis. Haematologica Vol.108 No.10 (2023) , 2743-2752. 2752. doi:10.3324/haematol.2022.282419 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/90697
Title
Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis
Author's Affiliation
Siriraj Hospital
Faculty of Medicine, Chiang Mai University
Udon Thani Center Hospital
Faculty of Medicine, Khon Kaen University
King Chulalongkorn Memorial Hospital
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Phramongkutklao College of Medicine
Faculty of Medicine, Chulalongkorn University
Faculty of Medicine, Chiang Mai University
Udon Thani Center Hospital
Faculty of Medicine, Khon Kaen University
King Chulalongkorn Memorial Hospital
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Phramongkutklao College of Medicine
Faculty of Medicine, Chulalongkorn University
Other Contributor(s)
Abstract
Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses.