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

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

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.

MeSH terms

  • Adolescent
  • Child
  • Female
  • Germ-Line Mutation / genetics
  • Hepatitis A Virus Cellular Receptor 2* / genetics
  • Humans
  • Lymphoma, T-Cell* / drug therapy
  • Lymphoma, T-Cell* / genetics
  • Lymphoma, T-Cell* / pathology
  • Male
  • Panniculitis* / drug therapy
  • Panniculitis* / genetics
  • Panniculitis* / pathology
  • Retrospective Studies
  • Southeast Asian People
  • Thailand
  • Treatment Outcome
  • Young Adult

Substances

  • Hepatitis A Virus Cellular Receptor 2
  • HAVCR2 protein, human

Supplementary concepts

  • Subcutaneous panniculitis-like T-cell lymphoma

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