Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2024, 168(2):167-176 | DOI: 10.5507/bp.2023.021

B cell subsets reconstitution and immunoglobulin levels in children and adolescents with B non-Hodgkin lymphoma after treatment with single anti CD20 agent dose included in chemotherapeutic protocols: single center experience and review of the literature

Eva Hlavackova1, 2, Zdenka Krenova2, Arpad Kerekes2, Peter Slanina1, Marcela Vlkova1
1 Department of Clinical Immunology and Allergology, St. Anne's University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
2 Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Czech Republic

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: rituximab, B non-Hodgkin lymphoma, chemotherapy, late complications of chemotherapy, hypogammaglobulinemia, children and adolescents

Received: September 30, 2022; Revised: March 29, 2023; Accepted: May 10, 2023; Prepublished online: May 23, 2023; Published: June 10, 2024  Show citation

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Hlavackova, E., Krenova, Z., Kerekes, A., Slanina, P., & Vlkova, M. (2024). B cell subsets reconstitution and immunoglobulin levels in children and adolescents with B non-Hodgkin lymphoma after treatment with single anti CD20 agent dose included in chemotherapeutic protocols: single center experience and review of the literature. Biomedical papers, 168(2), 167-176. doi: 10.5507/bp.2023.021
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    References

    1. Harker-Murray PD, Pommert L, Barth MJ. Novel Therapies Potentially Available for Pediatric B-Cell Non-Hodgkin Lymphoma. J Natl Compr Canc Netw 2020;18(8):1125-34. doi: 10.6004/jnccn.2020.7608 Go to original source... Go to PubMed...
    2. Anolik JH, Friedberg JW, Zheng B, Barnard J, Owen T, Cushing E, Kelly J, Milner E C, Fisher RI, Sanz I. B cell reconstitution after rituximab treatment of lymphoma recapitulates B cell ontogeny. Clin Immunol 2007;122(2):139-45. doi: 10.1016/j.clim.2006.08.009 Go to original source... Go to PubMed...
    3. Minard-Colin V, Aupérin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med 2020;382(23):2207-19. doi: 10.1056/NEJMoa1915315 Go to original source... Go to PubMed...
    4. Bollard CM, Lim MS, Gross TG. Committee CN-HL. Children's Oncology Group's 2013 blueprint for research: non-Hodgkin lymphoma. Pediatr Blood Cancer 2013;60(6):979-84. doi: 10.1002/pbc.24416 Go to original source... Go to PubMed...
    5. Minard-Colin V, Brugières L, Reiter A, Cairo MS, Gross TG, Woessmann W, Burkhardt B, Sandlund J T., Williams D, Pillon M. Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead. J Clin Oncol 2015;33(27):2963-74. doi: 10.1200/JCO.2014.59.5827 Go to original source... Go to PubMed...
    6. Burkhardt B, Oschlies I, Klapper W, Zimmermann M, Woessmann W, Meinhardt A, Landmann E, Attarbaschi A, Niggli F, Schrappe M. Non-Hodgkin's lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. Leukemia 2011;25(1):153-60. doi: 10.1038/leu.2010.245 Go to original source... Go to PubMed...
    7. Meinhardt A, Burkhardt B, Zimmermann M, Borkhardt A, Kontny U, Klingebiel T, Berthold F, Janka-Schaub G, Klein C, Kabickova E, Klapper W, Attarbachi A, Schrappe M, Reiter A. Group, B.-F.-M. 2010 Phase II window study on rituximab in newly diagnosed pediatric mature B-cell non-Hodgkin's lymphoma and Burkitt leukemia B J Clin Oncol 2010;28(19):3115-21. doi: 10.1200/JCO.2009.26.6791 Go to original source... Go to PubMed...
    8. Bethke M, Varga G, Weinhage T, Sabharwal H, Mellgren K, Randau G, Rolfing M, Wittkowski H, Foell D, Michgehl U, Burghardt B. Patient parameters and response after administration of rituximab in pediatric mature B-cell non-Hodgkin lymphoma. Pediatr Blood Cancer 2022;69(4):e29514. doi: 10.1002/pbc.29514 Go to original source... Go to PubMed...
    9. Christou EAA, Giardino G, Worth A, Ladomenou F. Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab. Int Rev Immunol 2017;36(6):352-59. doi: 10.1080/08830185.2017.1346092 Go to original source... Go to PubMed...
    10. Kaplan B, Kopyltsova Y, Khokhar, Lam F, Bonagura V. Rituximab and immune deficiency: case series and review of the literature. J Allergy Clin Immunol Pract 2014;2(5):594-600. doi: 10.1016/j.jaip.2014.06.003 Go to original source... Go to PubMed...
    11. Kaplan B, Bonagura VR. Secondary Hypogammaglobulinemia: An Increasingly Recognized Complication of Treatment with Immunomodulators and After Solid Organ Transplantation. Immunol Allergy Clin North Am 2019;39(1):31-47. doi: 10.1016/j.iac.2018.08.005 Go to original source... Go to PubMed...
    12. Semchenkova A, Zhogov V, Rudneva A, Potapenko L, Plyasunova S, Miakova N, Samochatova E, Maschan A, Popov A. Immune reconstitution following rituximab-based immunochemotherapy in pediatric patients with B-cell non-Hodgkin lymphomas. Leuk Lymphoma 2022;63(1):217-21. doi: 10.1080/10428194.2021.1998486 Go to original source... Go to PubMed...
    13. Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant 2006;6(5 Pt 1):859-66. doi: 10.1111/j.1600-6143.2006.01288.x Go to original source... Go to PubMed...
    14. Worch J, Makarova O, Burkhardt B. Immunreconstitution and infectious complications after rituximab treatment in children and adolescents: what do we know and what can we learn from adults? Cancers (Basel) 2015;7(1):305-28. doi: 10.3390/cancers7010305 Go to original source... Go to PubMed...
    15. Wijetilleka S, Mukhtyar C, Jayne D, Ala A, Bright P, Chinoy H, Harper L, Kazmi M, Kiani-Alikhan S, Li C Misbach S, Oni L, Price-Kuehne F, Salama A, Workman S, Wrench D, Karim MY. Immunoglobulin replacement for secondary immunodeficiency after B-cell targeted therapies in autoimmune rheumatic disease: Systematic literature review. Autoimmun Rev 2019;18(5):535-41. doi: 10.1016/j.autrev.2019.03.010 Go to original source... Go to PubMed...
    16. Khojah A M, Miller ML, Klein-Gitelman M S, Curran ML, Hans V, Pachman LM, Fuleihan RL. Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases. Pediatr Rheumatol Online J 2019;17(1):61. doi: 10.1186/s12969-019-0365-y Go to original source... Go to PubMed...
    17. Ottaviano G, Marinoni M, Graziani S, Sibson K, Barzaghi F, Bertolini P, Chini L, Corti P, Cancrini C, D'Alba I, Gabelli M, Gallo V, Giancotta C, Giordano P, Lassandro G, Martire B, Angarano R,Mastrodicasa E, Bava C, Miano M, Naviglio S, Verzegnassi F, Saracco P, Trizzino A, Biondi A, Pignata C, Moschese V. Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia. J Allergy Clin Immunol Pract 2020;8(1):273-82. doi: 10.1016/j.jaip.2019.07.032 Go to original source... Go to PubMed...
    18. Harms Pritchard G, Pepper M. Memory B cell heterogeneity: Remembrance of things past. J Leukoc Biol 2018;103(2):269-74. doi: 10.1002/JLB.4MR0517-215R Go to original source... Go to PubMed...
    19. Caraux A, Klein B, Paiva B, Bret C, Schmitz A, Fuhler GM, Bos NA, Johnsen H E, Orfao A, Perez-Andres, M. Network MS. Circulating human B and plasma cells. Age-associated changes in counts and detailed characterization of circulating normal CD138- and CD138+ plasma cells. Haematologica 2010;95(6):1016-20. doi: 10.3324/haematol.2009.018689 Go to original source... Go to PubMed...
    20. Perez-Andres M, Paiva B, Nieto WG, Carau A, Schmitz A, Almeida J, Vogt RF, Marti GE, Rawstron AC, Van Zelm MC,Van Dongen JJ, Johnsen HE, Klein B, Orfao A. Primary Health Care Group of Salamanca for the Study of MBL Human peripheral blood B-cell compartments: a crossroad in B-cell traffic. Cytometry B Clin Cytom 2010;78(Suppl 1):S47-60. doi: 10.1002/cyto.b.20547 Go to original source... Go to PubMed...
    21. Blanco E, Pérez-Andrés M, Arriba-Méndez S, Contreras-Sanfeliciano T, Criado I, Pelak O, Serra-Caetano, A, Romero A, Puig N, Remesal A, Torres Canziales J, López-Granados E, Kalina T, Sousa AE,van Zelm M, Van der Burg M, van Dongen JJM, Orfao A, Group EP Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood. J Allergy Clin Immunol 2018;141(6):2208-19.e16. doi: 10.1016/j.jaci.2018.02.017 Go to original source... Go to PubMed...
    22. Shapiro-Shelef M, Calame K. Regulation of plasma-cell development. Nat Rev Immunol 2005;5(3):230-42. doi: 10.1038/nri1572 Go to original source... Go to PubMed...
    23. Chang HD, Tokoyoda K, Radbruch A. Immunological memories of the bone marrow. Immunol Rev 2018;283(1):86-98. doi: 10.1111/imr.12656 Go to original source... Go to PubMed...
    24. Malney DG, Smith B, Rose A. Rituximab: mechanism of action and resistance. Semin Oncol 2002;29(1 Suppl 2):2-9. Go to original source... Go to PubMed...
    25. Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk 2013;13(2):106-11. doi: 10.1016/j.clml.2012.11.011 Go to original source... Go to PubMed...
    26. Lim SH, Zhang Y, Wang Z, Varadarajan R, Periman P, Esler WV. Rituximab administration following autologous stem cell transplantation for multiple myeloma is associated with severe IgM deficiency. Blood Mar 2004;103(5):1971-2. doi: 10.1182/blood-2003-12-4331 Go to original source... Go to PubMed...
    27. Nishio M, Endo T, Fujimoto K, Sato N, Sakai T, Obara M, Kumano K, Minauchi K, Koike T. Persistent panhypogammaglobulinemia with selected loss of memory B cells and impaired isotype expression after rituximab therapy for post-transplant EBV-associated autoimmune hemolytic anemia. Eur J Haematol 2005;75(6):527-9. doi: 10.1111/j.1600-0609.2005.00552.x Go to original source... Go to PubMed...
    28. Otani IM, Lehman HK, Jongco AM, Tsao LR, Azar AE, Tarrant TK, Engel E, Walter J E, Truong TQ, Khan D A, Ballow M, Cunningham-Rundles C, Lu H, Kwan M, Barmettler S. Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees. J Allergy Clin Immunol 2022;149(5):1525-60. doi: 10.1016/j.jaci.2022.01.025 Go to original source... Go to PubMed...
    29. Patel SY, Carbone J, Jolles S. The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management. Front Immunol 2019;10:33. doi: 10.3389/fimmu.2019.00033 Go to original source... Go to PubMed...
    30. Roberts DM, Jones RB, Smith RM, Alberici F, Kumaratne DS, Burns S, Jayne DR. Immunoglobulin G replacement for the treatment of infective complications of rituximab-associated hypogammaglobulinemia in autoimmune disease: a case series. J Autoimmun 2015;57:24-9. doi: 10.1016/j.jaut.2014.11.004 Go to original source... Go to PubMed...
    31. Jolles S, Chapel H, Litzman J. When to initiate immunoglobulin replacement therapy (IGRT) in antibody deficiency: a practical approach. Clin Exp Immunol 2017;188(3):333-41. doi: 10.1111/cei.12915 Go to original source... Go to PubMed...
    32. Barmettler S, Price C. Continuing IgG replacement therapy for hypogammaglobulinemia after rituximab-for how long? J Allergy Clin Immunol 2015;136(5):1407-9. doi: 10.1016/j.jaci.2015.06.035 Go to original source... Go to PubMed...
    33. Martín Ibáñez I, Arce Casas A, Cruz Martínez O, Estella Aguado J, Martín Mateos MA. Humoral immunity in pediatric patients with acute lymphoblastic leukaemia. Allergol Immunopathol (Madr) 2003;31(6):303-10. Go to original source... Go to PubMed...
    34. Lehrnbecher T, Schubert R, Behl M, Koenig M, Rose M. A, Koehl U, Meisel R, Laws HJ. Impaired pneumococcal immunity in children after treatment for acute lymphoblastic leukaemia. Br J Haematol 2009;147(5):700-5. doi: 10.1111/j.1365-2141.2009.07903.x Go to original source... Go to PubMed...
    35. Harrington DS, Weisenburger DD, Purtilo DT. Malignant lymphoma in the X-linked lymphoproliferative syndrome. Cancer 1987;59(8):1419-29. doi: 10.1002/1097-0142(19870415)59:83.0.co,2-p Go to original source...
    36. Del Mistro A, Laverda A, Calabrese F, De Martino M., Calabri G, Cogo P, Cocchi P, D'Andrea E De Rossi A, Giaquinto C. Primary lymphoma of the central nervous system in two children with acquired immune deficiency syndrome. Am J Clin Pathol 1990;94(6):722-8. doi: 10.1093/ajcp/94.6.722 Go to original source... Go to PubMed...
    37. Seidemann K, Tiemann M, Henze G, Sauerbrey A, Müller S, Reiter A. Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency: analysis of 19 patients from the BFM trials. Med Pediatr Oncol 1999;33(6):536-44. doi: 10.1002/(sici)1096-911x(199912)33:63.0.co,2-z Go to original source...
    38. Bhakta N, Liu Q, Ness KK, Baassiri M, Eissa H, Yeo F, Chemaitilly W, Ehrhardt MJ, Bass J, Bishop MW, Shelton K, Lu L, Huang S, Li Z, Caron E, Lanctot J, Howel C, Folse T, Joshi V, Green DM, Muldrooney DA, Armstrong GT, Krull KR, Brinkman TM,Khan RB,Srivastava DK, Hudson MM, Yasui Y, Robinson LL. The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet 2017;390(10112):2569-82. doi: 10.1016/S0140-6736(17)31610-0 Go to original source... Go to PubMed...
    39. Mulrooney DA., Hyun G, Ness KK, Bhakta N, Pui CH, Ehrhardt MJ, Krull KR, Crom DB, Chemaitilly W, Srivastava DK. The changing burden of long-term health outcomes in survivors of childhood acute lymphoblastic leukaemia: a retrospective analysis of the St Jude Lifetime Cohort Study. Lancet Haematol 2019;6(6):e306-e316. doi: 10.1016/S2352-3026(19)30050-X Go to original source... Go to PubMed...
    40. Ehrhardt MJ, Hochberg J, Bjornard KL, Brinkman TM. Long-term survivors of childhood, adolescent and young adult non-Hodgkin lymphoma. Br J Haematol 2019;185(6):1099-110. doi: 10.1111/bjh.15775 Go to original source... Go to PubMed...
    41. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol 2008;8(1):59-73. doi: 10.1038/nri2216 Go to original source... Go to PubMed...
    42. Chen J, Yang N, Liu H, Yao H, Wang J, Yang Y, Zhang W. Immunological effects of a low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor priming regimen on a mouse leukemia model. Oncol Lett 2018;16(3):3022-28. doi: 10.3892/ol.2018.9018 Go to original source... Go to PubMed...
    43. Di Francia R, Crisci S, De Monaco A., Cafiero C, Re A, Iaccarino G, De Filippi R, Frigeri F, Corazzelli G, Micera A, Pinto A. Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers. Cancers (Basel) 2021;13(5):966. doi: 10.3390/cancers13050966 Go to original source... Go to PubMed...
    44. Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 2013;65(2):157-70. doi: 10.1111/j.2042-7158.2012.01567.x Go to original source... Go to PubMed...
    45. Marco H,Smith RM, Jone RB, Guerry MJ, Catapano F Burns S, Chaudhry AN, Smith KG, Jayne DR. The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease. BMC Musculoskelet Disord 2014;15:178. doi: 10.1186/1471-2474-15-178 Go to original source... Go to PubMed...
    46. Roberts DM, Jones RB, Smith RM, Alberic F, Kumaratne DS, Burns S, Jayne DR. Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun 2015;57:60-5. doi: 10.1016/j.jaut.2014.11.009 Go to original source... Go to PubMed...
    47. Rosolen A., Perkins SL, Pinkerton CR, Guillerman RP, Sandlund JT, Patte C, Reiter A, Cairo MS. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol 2015;33(18):2112-8. doi: 10.1200/JCO.2014.59.7203 Go to original source... Go to PubMed...
    48. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J. Lymphoma classification--from controversy to consensus: the R.E.A.L. and WHO Classification of lymphoid neoplasms. Ann Oncol 2000;11(Suppl 1):3-10. Go to original source...
    49. Murphy SB. Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults. Semin Oncol 1980;7(3):332-9.
    50. Morbach H, Eichhorn EM, Liese JG, Girschick HJ. Reference values for B cell subpopulations from infancy to adulthood. Clin Exp Immunol 2010;162(2):271-9. doi: 10.1111/j.1365-2249.2010.04206.x Go to original source... Go to PubMed...
    51. Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, Cunningham-Rundles C, Etzioni A, Franco J L., Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Torgerson TR, Casanova JL, Sullivan KE, Tangye SG. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol 2020;40(1):66-81. doi: 10.1007/s10875-020-00758-x Go to original source... Go to PubMed...
    52. Gasteiger LM, Robinson PN, Pazmand J, Boztug K, Seppänen MRJ, Seidel MG; Registry Working Party of the European Society for Immunodeficiencies (ESID). Supplementation of the ESID registry working definitions for the clinical diagnosis of inborn errors of immunity with encoded human phenotype ontology (HPO) terms. J Allergy Clin Immunol Pract 2020;8(5):1778. doi: 10.1016/j.jaip.2020.02.019 Go to original source... Go to PubMed...
    53. Seide MG, Kindle G, Gathmann B, Quint I, Buckland M, van Montfrans J, Scheible R, Rusch S, Gasteiger L, M, Grimbacher B, Mahlaoui N, Ehl S, Collaborators ERWPA The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract 2019;7(6):1763-70. doi: 10.1016/j.jaip.2019.02.004 Go to original source... Go to PubMed...
    54. Giles A J., Hutchinson MND, Sonnemann HM, Jung J, Fecci PE, Ratnam NM, Zhang W, Song H, Bailey R, Davis D, Reid CM, Park DM,Gilbert MR. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer 2018;6(1):51. doi: 10.1186/s40425-018-0371-5 Go to original source... Go to PubMed...
    55. Nived P, Pettersson Å, Jönsson G, Bengtsson AA, Settergren B, Skattum L, Johansson Å, Kapetanovic MC. Methotrexate reduces circulating Th17 cells and impairs plasmablast and memory B cell expansions following pneumococcal conjugate immunization in RA patients. Sci Rep 2021;11(1):9199. doi: 10.1038/s41598-021-88491-2 Go to original source... Go to PubMed...
    56. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest 1998;102(2):322-8. doi: 10.1172/JCI2676 Go to original source... Go to PubMed...
    57. Rozkova D, Horvath R, Bartunkova J, Spisek R. Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors. Clin Immunol 2006;120(3):260-71. doi: 10.1016/j.clim.2006.04.567 Go to original source... Go to PubMed...
    58. Kuppner MC, Bleifuss E, Noessner E, Mocikat R, Hesler C, Mayerhofer C. Differential effects of ifosfamide on dendritic cell-mediated stimulation of T cell interleukin-2 production, natural killer cell cytotoxicity and interferon-gamma production. Clin Exp Immunol 2008;153(3):429-38. doi: 10.1111/j.1365-2249.2008.03708.x Go to original source... Go to PubMed...
    59. Gottenberg JE, Ravaud P, Bardin T, Cacoub P, Cantagrel A, Combe B, Dougados M, Flipo RM, Godeau B, Guillevin L, Le Löet X, Hachulla E, Schaeverbeke T, Sibilia J, Baron G, Mariette X. AutoImmunity and Rituximab registry and French Society of Rheumatology Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry. Arthritis Rheum 2010;62(9):2625-32. doi: 10.1002/art.27555 Go to original source... Go to PubMed...
    60. Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U. Post-rituximab immunoglobulin M (IgM) hypogammaglobulinemia. Autoimmun Rev 2020;19(3):102466. doi: 10.1016/j.autrev.2020.102466 Go to original source... Go to PubMed...
    61. Ghielmin M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M,Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 2004;103(12):4416-23. doi: 10.1182/blood-2003-10-3411 Go to original source... Go to PubMed...
    62. Rao A, Kelly M, Musselman M, Ramadas J, Wilson D, Grossman W, Shenoy S. Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias. Pediatr Blood Cancer 2008;50(4):822-5. doi: 10.1002/pbc.21264 Go to original source... Go to PubMed...
    63. Venhoff N, Effelsberg NM, Salzer U, Warnatz K, Peter HH, Lebrecht D, Schlesie M, Voll RE. Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides. PLoS One 2012;7(5):e3762. doi: 10.1371/journal.pone.0037626 Go to original source... Go to PubMed...
    64. Makatsori M, Kiani-Alikhan S, Manson AL, Verma N, Leandro M, Gurugama NP, Longhurst HJ, Grigoriadou S, Buckland M, Kanfer E, Hanson S, Ibrahim MA, Grimbacher B, Chee R, Seneviratne SL. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. QJM 2014;107(10):821-8. doi: 10.1093/qjmed/hcu094 Go to original source... Go to PubMed...
    65. Pearso ADJ, Scobie N, Norga K, Ligas F, Chiodin D, Burke A, Minard-Colin V, Adamson P, Marshall LV, Balakumaran A, Benettaib B, Bhargava P, Bollard CM, Bolotin E, Bomken S, Buechner J, Burkhardt B, Caron H, Copland C, Demolis P, Egorov A, Farham M, Zugmaier G, Gross T, Horton-Taylor D, Klapper W, Lesa G, Marcus R, Miles RR, Nottage K, Pacaud L, Ricafort R, Schrappe M, Sterba J, Vezan R, weiner S, Kim S.Y, Reaman G, Vassal G. ACCELERATE and European Medicine Agency Paediatric Strategy Forum for medicinal product development for mature B-cell malignancies in children. Eur J Cancer 2019;110:74-85. doi: 10.1016/j.ejca.2019.01.013 Go to original source... Go to PubMed...
    66. Labrosse R, Barmettler S, Derfalvi B, Blincoe A, Cros G, Lacombe-Barrios J, Barsalou J, Yang N, Alrumayyan N, Sinclair J, Ong MS, Camrgo CA, Walter J, Haddad E. Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients. J Allergy Clin Immunol 2021;148(2):523-32.e8. doi: 10.1016/j.jaci.2021.03.041 Go to original source... Go to PubMed...
    67. Deyà-Martínez A, Gordón Y, Molina-Anguita C, Vlagea A, Piquer M, Juan M, Esteve-Solé A, Antón J, Madrid Á, García-García A, Plaza AM, Armanguf T, Alsina L. Single-cycle rituximab-induced immunologic changes in children: Enhanced in neuroimmunologic disease? Neurol Neuroimmunol Neuroinflamm 2020;7(4):e724. doi: 10.1212/NXI.0000000000000724 Go to original source... Go to PubMed...
    68. Zarkhin V, Li L, Kambham N, Sigdel T, Salvatierra O, Sarwal MM. A randomized, prospective trial of rituximab for acute rejection in pediatric renal transplantation. Am J Transplant 2008;8(12):2607-17. doi: 10.1111/j.1600-6143.2008.02411.x Go to original source... Go to PubMed...
    69. Willems M, Haddad E, Niaudet P. Koné-Paut I, Bensman A, Cochat P, Deschênes G, Fakhouri F, Leblanc T, Llanas B, Liorat T, Pillet P, Ranchin B, Salomon R, Ulinski T, Bader-Meunier B, French Pediatric-Onset SLE Study GroupRituximab therapy for childhood-onset systemic lupus erythematosus. J Pediatr 2006;148(5):623-27. doi: 10.1016/j.jpeds.2006.01.041 Go to original source... Go to PubMed...
    70. Ghielmini M, Rufibach K, Salles G, Leoncini-Franscini L, Léger-Falandry C, Cogliatti S, Fey M, Martinelli G, Stahel R, Lohri A, Ketter N, Wernli M, Cerny T, Schmitz SF. Single agent rituximab in patients with follicular or mantle cell lymphoma: clinical and biological factors that are predictive of response and event-free survival as well as the effect of rituximab on the immune system: a study of the Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol 2005;16(10):1675-82. doi: 10.1093/annonc/mdi320 Go to original source... Go to PubMed...
    71. Zarkhin V, Lovelace PA, Li L, Hsieh SC, Sarwal MM. Phenotypic evaluation of B-cell subsets after rituximab for treatment of acute renal allograft rejection in pediatric recipients. Transplantation 2011;91(9):1010-8. doi: 10.1097/TP.0b013e318213df29 Go to original source... Go to PubMed...
    72. Pi±tosa B, Wolska-Ku¶nierz B, Pac M, Siewiera K, Gałkowska E, Bernatowska E. B cell subsets in healthy children: reference values for evaluation of B cell maturation process in peripheral blood. Cytometry B Clin Cytom 2010;78(6):372-81. doi: 10.1002/cyto.b.20536 Go to original source... Go to PubMed...
    73. van Gent R. van Tilburg CM, Nibbelke EE, Otto SA, Gaiser J F, Janssens-Korpela PL, Sanders EA, Borghans J. A, Wulffraat N M, Bierings MB, Bloem AC, Tesselaar K. Refined characterization and reference values of the pediatric T- and B-cell compartments. Clin Immunol 2009;133(1):95-107. doi: 10.1016/j.clim.2009.05.020 Go to original source... Go to PubMed...
    74. Mei HE, Frölich D, Giesecke C, Loddenkemper C, Reiter K, Schmidt S, Feist E, Daridon C, Tony HP, Radbruch A. Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab. Blood 2010;116(24):5181-90. doi: 10.1182/blood-2010-01-266536 Go to original source... Go to PubMed...
    75. Barmettler S, Ong MS, Farmer JR, Choi H, Walter J. Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia. JAMA Netw Open 2018;1(7):e184169. doi: 10.1001/jamanetworkopen.2018.4169 Go to original source... Go to PubMed...
    76. Diwakar L, Gorrie S, Richter A, Chapman O, Dhillon P, Al-Ghanmi F, Noorani S, Krishna MT, Huissoon A Does rituximab aggravate pre-existing hypogammaglobulinaemia? J Clin Pathol 2010;63(3):275-7. doi: 10.1136/jcp.2009.068940 Go to original source... Go to PubMed...
    77. Yri OE, Torfoss D, Hungnes O, Tierens A, Waalen K, Nordøy T, Dudman S, Kilander A, Wader KF, Ostenstad B, Ekanger R, Mezer P. Kolstad ARituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. Blood 2011;118(26):6769-71. doi: 10.1182/blood-2011-08-372649 Go to original source... Go to PubMed...
    78. Bedognetti D, Zoppoli G, Massucco C, Zanardi E, Zupo S, Bruzzone A, Sertoli MR, Balleari E, Racchi O, Messina M,Caltabiano G, Icardi G, Durando P, Marincola FM, Boccardo F, Ferrarini M, Ansaldi E, DeMaria A. Impaired response to influenza vaccine associated with persistent memory B cell depletion in non-Hodgkin's lymphoma patients treated with rituximab-containing regimens. J Immunol 2011;186(10):6044-55. doi: 10.4049/jimmunol.1004095 Go to original source... Go to PubMed...
    79. Rapezzi D, Sticchi L, Racchi O, Mangerini R, Ferraris AM, Gaetani GF. Influenza vaccine in chronic lymphoproliferative disorders and multiple myeloma. Eur J Haematol 2003;70(4):225-30. doi: 10.1034/j.1600-0609.2003.00028.x Go to original source... Go to PubMed...
    80. Feery BJ, Sullivan JR, Hurley TH, Evered MG. Immunization with influenza vaccine in patients with haematological malignant disease. Med J Aust 1977;1(9):292-4. doi: 10.5694/j.1326-5377.1977.tb130704.x Go to original source... Go to PubMed...
    81. Cha Z, Li C, Zang Y, Gu H, Guo H, Li J, Fang Y, Petersen T, Karas RO, Hamilton ML, Qian B. Adaptive B cell responses in rituximab-treated diffuse large B cell lymphoma patients during complete remission. Tumour Biol 2016;37(1):829-35. doi: 10.1007/s13277-015-3872-6 Go to original source... Go to PubMed...
    82. Kelesidis T, Daikos G, Boumpas D, Tsiodras S. Does rituximab increase the incidence of infectious complications? A narrative review. Int J Infect Dis 2011;15(1):e2-16. doi: 10.1016/j.ijid.2010.03.025 Go to original source... Go to PubMed...
    83. Castagnola E, Dallorso S, Faraci M, Morreale G, Di Martino D, Cristina E, Scarso L, Lanino E. Long-lasting hypogammaglobulinemia following rituximab administration for Epstein-Barr virus-related post-transplant lymphoproliferative disease preemptive therapy. J Hematother Stem Cell Res 2003;12(1):9-10. doi: 10.1089/152581603321210082 Go to original source... Go to PubMed...
    84. Fleury I, Chevret S, Pfreundschuh M, Salles G, Coiffier B, van Oer MH, Gisselbrecht C, Zucca E, Herold M, Ghielmini M, Thieblemont C. Rituximab and risk of second primary malignancies in patients with non-Hodgkin lymphoma: a systematic review and meta-analysis. Ann Oncol 2016;27(3):390-7. doi: 10.1093/annonc/mdv616 Go to original source... Go to PubMed...
    85. Riaz IB, Faridi W, Patnaik MM, Abraham RS. A Systematic Review on Predisposition to Lymphoid (B and T cell) Neoplasias in Patients With Primary Immunodeficiencies and Immune Dysregulatory Disorders (Inborn Errors of Immunity). Front Immunol 2019;10:777. doi: 10.3389/fimmu.2019.00777 Go to original source... Go to PubMed...
    86. Hauck F, Voss R, Urban C, Seidel MG. Intrinsic and extrinsic causes of malignancies in patients with primary immunodeficiency disorders. J Allergy Clin Immunol 2018;141(1):59-68.e4. doi: 10.1016/j.jaci.2017.06.009 Go to original source... Go to PubMed...

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