In children under 3 years of age, lymphoma is extremely rare and may be a manifestation of inborn errors of immunity (IEIs). The aim of this study was to determine TREC/KREC copy numbers and search for Slavic founder mutations (RAG1 p.Lys86ValfsTer33, IL7R p.Ser44Arg, NBN1 p.Lys219AsnfsTer16, ATM p.Glu1978Ter, UNC13D p.Arg782SerfsTer12) in patients with lymphoma up to 3 years of age from the Belarusian Cancer Registry (No.: 0170100025) over a 26-year period.
From 1998 to 2024, 39 patients younger than 3 years (29 males and 10 females) were diagnosed with lymphoma. The median age was 2.1 years (from 50 days to 2.8 years). 4 patients had Hodgkin's lymphoma (HL), 5—diffuse large B cell lymphoma (DLBCL), 13—lymphoblastic lymphoma (LL), 10—Burkitt lymphoma (BL), 2—peripheral T cell lymphoma (PTCL), 4—anaplastic large cell lymphoma (ALCL), 1—non-Hodgkin's lymphoma (NHL) of unspecified type. DNA was isolated from archival samples from 36 patients: bone marrow smears (n = 12), frozen bone marrow cells (n = 11), and peripheral blood cells (n = 13).
Lymphoma in children aged 0-3 years accounted 3% (39/1237) of all pediatric lymphoma cases up to 18 years of age, including 7% (35/481) of NHL and 0.5% (4/756) of HL patients. 15/39 (38%) patients died and 3 were lost to follow-up. TREC/KREC copy numbers was reduced in 12/36 (33%) patients, 7 of whom were dead. Low TRECs/KRECs were present in all patients with DLBCL, 2 with ALCL, 2 with LL, and single cases with HL, BL, and PTCL. Homozygosity for the underlying Slavic variant of RAG1 [p.Lys86ValfsTer33] was found in a patient with DLBCL at the age of 14 months. One 12-month-old patient with PTCL was homozygous for the founder Slavic UNC13D variant [p.Arg782SerfsTer12].
Low TREC/KREC was detected in one-third of children aged 0-3 years with lymphoma and may be used as a step 1 method to suspect the IEIs.
