Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency: Analysis of 19 patients from the BFM trials

Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations

“…Therefore, it is absolutely essential to postulate criteria for the early and certain recognition of NBS in order to avoid the conventional treatment protocols in cases where a malignancy is already present. 10 This must hold not only for the Slav populations studied, but also for NBS patients 3 This is supported by recent findings of decreased DNA stability and higher incidence of malignancy in heterozygous relatives of NBS patients of Slav origin (Novotna B, 1999) and by the association of NBS1 mutations with childhood acute lymphoblastic leukemia (Varon et al 11 ). Therefore, carriers of NBS1 mutation should avoid ionising radiation and also receive modified treatment protocols in cases of malignancy.…”

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Primary immunodeficiencies (PID) such as DNA repair defects (Nijmegen breakage syndrome, Ataxia telangiectasia, Bloom syndrome or constitutional mismatch repair deficiency), severe combined immunodeficiencies (SCID), common variable immunodeficiencies (CVID), and immune-osseous dysplasias (Di George syndrome or cartilage hair hypoplasia) have an extraordinary risk of developing leukemia and lymphoma. [5][6][7][8][9][10][11][12][13][14][15][16][17]20,21 Although these patients seem to have an inferior prognosis and an increased risk of treatment-related toxicity and death compared to patients with lymphoid malignancies without a PID, curative therapies including allogeneic stem cell transplantation (allo-SCT) have been repeatedly reported. 5,6,10,11,15,16,22 Systematic data on the spectrum of common and rare pre-existing conditions associated with NHL in children and adolescents are scarce with respect to the type of the pre-existing conditions and the clinical characteristics and outcome of the associated NHL subtypes.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17]20,21 Although these patients seem to have an inferior prognosis and an increased risk of treatment-related toxicity and death compared to patients with lymphoid malignancies without a PID, curative therapies including allogeneic stem cell transplantation (allo-SCT) have been repeatedly reported. 5,6,10,11,15,16,22 Systematic data on the spectrum of common and rare pre-existing conditions associated with NHL in children and adolescents are scarce with respect to the type of the pre-existing conditions and the clinical characteristics and outcome of the associated NHL subtypes. Thus, the two largest childhood NHL consortia, the European Intergroup for Childhood NHL (EICNHL) and the international Berlin-Frankfurt-Münster (i-BFM) Study Group (SG), designed a retrospective multinational study to collect data on unselected types of pre-existing conditions among children and adolescents with NHL.…”

The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control

“…The hypomorphic mutations which lead to decreased function of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), a rare autosomal recessive hereditary disorder that imparts an increased predisposition to the development of malignancy [10][11][12]. In the Polish NBS registry, 18 of 48 patients had developed lymphomas by the age of 15 [13]. Other types of cancers are also reported in the NBS1 compromised population [14].…”

“…Several serine/glutamine motifs, consensus sequences of phosphorylation by ATM and ATM/RAD3-related (ATR), are found at the central region of NBS1. In particular, the serine residues at 278 and 343 are phosphorylated by ATM kinase in response to ionizing radiation both in vitro and in vivo, and such phosphorylation is responsible for intra-S phase checkpoint control [14,15] and telomere maintenance [11,13,16].…”