title: Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome.
abstract: Nijmegen breakage syndrome (NBS, MIM #251260) is an autosomal recessive chromosomal instability disorder. Majority of patients affected are of Slavic origin and share the same founder mutation of 657del5 within the NBN gene encoding protein involved in DNA double-strand breaks repair. Clinically, this is characterized by a microcephaly, immunodeficiency and a high incidence of pediatric malignancies, mostly lymphomas and leukemias. Anticancer treatment among patients with NBS is challenging because of a high risk of life threatening therapy-related toxicity including severe infections, bone marrow failure, cardio- and nephrotoxicity and occurrence of secondary cancer. Based on systemic review of available literature and the Polish acute lymphoblastic leukemia database we concluded that among patients with NBS, these who suffered from clinically proven severe immunodeficiency are at risk of the complications associated with oncological treatment. Thus, in this group it reasonable to reduce chemotherapy up to 50% especially concerning anthracyclines methotrexate, alkylating agents and epipodophyllotoxines, bleomycin and radiotherapy should be omitted. Moreover, infection prophylaxis using intravenous immunoglobulin supplementation together with antifungal and antibacterial agent is recommended. To replace radiotherapy or some toxic anticancer agents targeted therapy using monoclonal antibodies and kinase inhibitors or bone marrow transplantation with reduced-intensity conditioning should be considered in some cases, however, this statement needs further studies.
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Pastorczak
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Diabetology, Medical University of Lodz, Poland. Electronic address: wojciech.mlynarski@umed.lodz.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D007239:Infections / Q000209:etiology; D007945:Leukemia, Lymphoid / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D008223:Lymphoma / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology; D049932:Nijmegen Breakage Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D010641:Phenotype; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D012306:Risk; D016896:Treatment Outcome
keywords: Leukemia; Lymphoma; Nijmegen-breakage syndrome; Treatment