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. 2024 Nov 13;19(1):426.
doi: 10.1186/s13023-024-03438-w.

Characteristics and therapeutic outcomes of subcutaneous panniculitis-like T-cell lymphoma with and without germline HAVCR2 mutations in Thai children and adolescents

Pimpitcha Youthong  1 , Samart Pakakasama  2 , Patcharee Komvilaisak  3 , Piya Rujkijyanont  4 , Chane Choed-Amphai  5 , Kamon Phuakpet  6 , Chatphatai Moonla  7   8 , Chantana Polprasert  7   8 , Darintr Sosothikul  9   10
Affiliations

Characteristics and therapeutic outcomes of subcutaneous panniculitis-like T-cell lymphoma with and without germline HAVCR2 mutations in Thai children and adolescents

Pimpitcha Youthong et al. Orphanet J Rare Dis. .

Abstract

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma associated with hemophagocytic lymphohistiocytosis (HLH)/HLH-like systemic illnesses and germline HAVCR2 mutations. Although previous studies suggested successful treatment of SPTCL with immunosuppressive therapy (IST) without chemotherapy, IST data in pediatric SPTCL remain scarce. To explore characteristics and therapeutic outcomes, comparing IST-based and chemotherapy-based regimens in pediatric SPTCL, in this retrospective cohort study, patients with SPTCL diagnosed at age ≤20 years during 2007-2023 were enrolled from 6 hematology/oncology centers in Thailand. HAVCR2 exon 2 sequencing was performed using DNA extracted from peripheral blood or bone marrow. Presence of HLH/HLH-like systemic illnesses, treatment outcomes, and adverse events (AEs) were reviewed and analyzed.

Results: Of 22 patients with SPTCL (median age at diagnosis, 11.5 years [range, 6.0-19.0]; 63.6% males), 86.4% harbored germline HAVCR2 mutation, either homozygous (77.3%) or heterozygous (9.1%) p.Y82C variant, while 68.2% developed HLH/HLH-like systemic illnesses. Overall, 36.4% received IST as first-line treatment. Durable complete remission (CR) was achieved in 71.4% and 50.0% after first-line chemotherapy and IST, respectively (P=0.45); however, chemotherapy tended to increase any AEs compared to IST (57.1% vs. 12.5%; P=0.07). The most common AEs were hypertension (27.3%), febrile neutropenia (18.2%), and fungal infection (13.6%). Among the relapsed cases, 71.4% could reach CR after subsequent-line therapy. Fatality (4.5%) only occurred in the chemotherapy group.

Conclusions: Pediatric SPTCL in Thailand frequently involves germline HAVCR2 mutations and/or HLH/HLH-like systemic illnesses. With comparable response and modest therapy-related toxicity, IST-based regimens may alternatively be considered as first-line treatment for pediatric SPTCL.

Keywords: HAVCR2; Children; Hemophagocytic lymphohistiocytosis; Immunosuppressive agent; Subcutaneous panniculitis-like T-cell lymphoma.

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Conflict of interest statement

Declarations Ethical approval and consent to participate The study protocol was ethically approved by the Institutional Review Boards of all the study sites, including the central study site at the Faculty of Medicine, Chulalongkorn University (IRB no. 0607/65). Written informed consent forms were obtained from each patient and/or their parents/guardians prior to participation in the study, in accordance with the Declaration of Helsinki. Consent for publication Not applicable Competing interests The authors declare that they have no competing interests.

References

    1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. - PMC - PubMed
    1. Lewis NE, Zhou T, Dogan A. Biology and genetics of extranodal mature T-cell and NK-cell lymphomas and lymphoproliferative disorders. Haematologica. 2023;108(12):3261–77. - PMC - PubMed
    1. Gonzalez CL, Medeiros LJ, Braziel RM, Jaffe ES. T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol. 1991;15:17–27. - PubMed
    1. Willemze R, Jansen PM, Cerroni L, et al. Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC cutaneous lymphoma group study of 83 cases. Blood. 2008;111(2):838–45. - PubMed
    1. Gayden T, Sepulveda FE, Khuong-Quang DA, et al. Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome. Nat Genet. 2018;50(12):1650–7. - PubMed

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