BACKGROUND: RTX, an anti-CD20 monoclonal antibody, added to chemotherapy has proven to be effective in children and adolescents with high-grade, high-risk and matured non-Hodgkin lymphoma. RTX leads to prompt CD19+ B lymphocyte depletion. However, despite preserved immunoglobulin production by long-lived plasmablasts after treatment, patients remain at risk of prolonged hypogammaglobulinemia. Further, there are few general guidelines for immunology laboratories and clinical feature monitoring after B cell-targeted therapies. The aim of this paper is to describe B cell reconstitution and immunoglobulin levels after pediatric B-NHL protocols, that included a single RTX dose and to review the literature. METHODS: A retrospective single-center study on the impact of a single RTX dose included in a chemotherapeutic pediatric B Non-Hodgkin Lymphoma (B-NHL) treatment protocols. Immunology laboratory and clinical features were evaluated over an eight hundred days follow-up (FU) period, after completing B-NHL treatment. RESULTS: Nineteen patients (fifteen Burkitt lymphoma, three Diffuse large B cell lymphoma, and one Marginal zone B cell lymphoma) fulfilled the inclusion criteria. Initiation of B cell subset reconstitution occurred a median of three months after B-NHL treatment. Naïve and transitional B cells declined over the FU in contrast to the marginal zone and the switched memory B cell increase. The percentage of patients with IgG, IgA, and IgM hypogammaglobulinemia declined consistently over the FU. Prolonged IgG hypogammaglobulinemia was detectable in 9%, IgM in 13%, and IgA in 25%. All revaccinated patients responded to protein-based vaccines by specific IgG antibody production increase. Following antibiotic prophylaxes, none of the patients with hypogammaglobulinemia manifested with either a severe or opportunistic infection course. CONCLUSION: The addition of a single RTX dose to the chemotherapeutic treatment protocols was not shown to increase the risk of developing secondary antibody deficiency in B-NHL pediatric patients. Observed prolonged hypogammaglobulinemia remained clinically silent. However interdisciplinary agreement on regular long-term immunology FU after anti-CD20 agent treatment is required.

• Keywords
• B non-Hodgkin lymphoma, chemotherapy, children and adolescents, hypogammaglobulinemia, late complications of chemotherapy, rituximab,
• MeSH
• Lymphoma, B-Cell drug therapy   immunology   MeSH
• Child MeSH
• Immunoglobulins administration & dosage   MeSH
• Humans MeSH
• Adolescent MeSH
• Lymphoma, Non-Hodgkin drug therapy   immunology   MeSH
• B-Lymphocyte Subsets immunology   drug effects   MeSH
• Child, Preschool MeSH
• Antineoplastic Agents, Immunological administration & dosage   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Retrospective Studies MeSH
• Rituximab * therapeutic use   administration & dosage   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Immunoglobulins MeSH
• Antineoplastic Agents, Immunological MeSH
• Rituximab * MeSH

Patients with double stranded DNA repair disorders (DNARDs) (Ataxia Telangiectasia (AT) and Nijmegen Breakage syndrome (NBS)) are at a very high risk for developing hematological malignancies in the first two decades of life. The most common neoplasms are T-cell lymphoblastic malignancies (T-cell ALL and T-cell LBL) and diffuse large B cell lymphoma (DLBCL). Treatment of these patients is challenging due to severe complications of the repair disorder itself (e.g., congenital defects, progressive movement disorders, immunological disturbances and progressive lung disease) and excessive toxicity resulting from chemotherapeutic treatment. Frequent complications during treatment for malignancies are deterioration of pre-existing lung disease, neurological complications, severe mucositis, life threating infections and feeding difficulties leading to significant malnutrition. These complications make modifications to commonly used treatment protocols necessary in almost all patients. Considering the rarity of DNARDs it is difficult for individual physicians to obtain sufficient experience in treating these vulnerable patients. Therefore, a team of experts assembled all available knowledge and translated this information into best available evidence-based treatment recommendations.

• Keywords
• Ataxia Telangiectasia, DNA repair disorder, Nijmegen breakage syndrome, clinical management, leukemia, lymphoma,
• Publication type
• Journal Article MeSH
• Review MeSH

Humoral deficiencies represent a broad group of disorders. The aim of the study was to compare the levels of antibodies against pneumococcal capsular polysaccharides (anti-PCP) and natural anti-galactosyl (anti-Gal) antibodies in (1) patients with chronic lymphocytic leukaemia (CLL), (2) patients with common variable immunodeficiency (CVID), and (3) a healthy population and to explore their diagnostic and prognostic potential. Serum immunoglobulin levels and levels of anti-Gal IgG, IgA, and IgM and anti-PCP IgG and IgG2 were determined in 59 CLL patients, 30 CVID patients, and 67 healthy controls. Levels of IgG, IgA, IgM, anti-Gal IgA, anti-Gal IgM, and anti-PCP IgA were lower in CLL and CVID patients than in healthy controls (p value for all parameters < 0.0001). Decrease in the levels of IgA, IgM, anti-Gal IgA, and anti-PCP IgA was less pronounced in the CLL group than in the CVID group. IgA decline, anti-Gal IgA, anti-PCP IgA, and anti-PCP IgG2 were negatively correlated with CLL stage. We devise the evaluation of anti-Gal antibodies to be a routine test in humoral immunodeficiency diagnostics, even in cases of immunoglobulin substitution therapy. Significant reductions, mainly in anti-Gal IgA, IgM, and anti-PCP IgA levels, may have prognostic importance in CLL patients.

• MeSH
• Autoantibodies blood   MeSH
• Bacterial Capsules immunology   MeSH
• Common Variable Immunodeficiency diagnosis   immunology   MeSH
• Biomarkers blood   MeSH
• Adult MeSH
• Galactosylceramides immunology   MeSH
• Immunity, Humoral MeSH
• Immunoglobulin A blood   MeSH
• Immunoglobulin G blood   MeSH
• Immunoglobulin M blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Pneumococcal Infections diagnosis   immunology   MeSH
• Prognosis MeSH
• Antibodies, Bacterial blood   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Streptococcus pneumoniae immunology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Autoantibodies MeSH
• Biomarkers MeSH
• Galactosylceramides MeSH
• Immunoglobulin A MeSH
• Immunoglobulin G MeSH
• Immunoglobulin M MeSH
• Antibodies, Bacterial MeSH