Abstract：Intravenous immunoglobulin (IVIG) has been widely used in chemotherapy for hematological malignancies, targeted therapy, and hematopoietic stem cell transplantation; however, there are still no available guidelines or consensus statements on the application of IVIG in pediatric hematological/neoplastic diseases at present in China and overseas. This consensus is developed based on the research advances in the application of IVIG in pediatric hematological/neoplastic diseases across the world and provides detailed recommendations for the clinical application of IVIG in pediatric hematological/neoplastic diseases and the prevention and treatment of related adverse reactions.
Pediatric Branch of Guangdong Medical Association,Editorial Department of Chinese Journal of Contemporary Pediatrics. Pediatric expert consensus on the application of intravenous immunoglobulin in children with hematological/neoplastic diseases[J]. CJCP, 2021, 23(4): 319-327.
Prins C, Gelfand EW, French LE. Intravenous immunoglobulin:properties, mode of action and practical use in dermatology[J]. Acta Derm Venereol, 2007, 87(3):206-218.
[4]
Imbach P, Barandun S, d'Apuzzo V, et al. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood[J]. Lancet, 1981, 1(8232):1228-1231.
[5]
Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia[J]. Blood Adv, 2019, 3(22):3780-3817.
[6]
Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia[J]. Blood, 2010, 115(2):168-186.
[7]
Ekert H. Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood[J]. Lancet, 1985, 2(8467):1310.
[8]
Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children:report from an international working group[J]. Blood, 2009, 113(11):2386-2393.
[9]
Qin YH, Zhou TB, Su LN, et al. The efficacy of different dose intravenous immunoglobulin in treating acute idiopathic thrombocytopenic purpura:a meta-analysis of 13 randomized controlled trials[J]. Blood Coagul Fibrinolysis, 2010, 21(8):713-721.
[10]
Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia[J]. Blood, 2011, 117(16):4190-4207.
[11]
Benesch M, Kerbl R, Lackner H, et al. Low-dose versus high-dose immunoglobulin for primary treatment of acute immune thrombocytopenic purpura in children:results of a prospective, randomized single-center trial[J]. J Pediatr Hematol Oncol, 2003, 25(10):797-800.
[12]
Alioglu B, Ercan S, Tapci AE, et al. A comparison of intravenous immunoglobulin (2 g/kg totally) and single doses of anti-D immunoglobulin at 50μg/kg, 75μg/kg in newly diagnosed children with idiopathic thrombocytopenic purpura:Ankara hospital experience[J]. Blood Coagul Fibrinolysis, 2013, 24(5):505-509.
[13]
Zanella A, Barcellini W. Treatment of autoimmune hemolytic anemias[J]. Haematologica, 2014, 99(10):1547-1554.
[14]
Anderson D, Ali K, Blanchette V, et al. Guidelines on the use of intravenous immune globulin for hematologic conditions[J]. Transfus Med Rev, 2007, 21(2 Suppl 1):S9-S56.
[15]
Hilgartner MW, Bussel J. Use of intravenous gamma globulin for the treatment of autoimmune neutropenia of childhood and autoimmune hemolytic anemia[J]. Am J Med, 1987, 83(4A):25-29.
[16]
Flores G, Cunningham-Rundles C, Newland AC, et al. Efficacy of intravenous immunoglobulin in the treatment of autoimmune hemolytic anemia:results in 73 patients[J]. Am J Hematol, 1993, 44(4):237-242.
[17]
Davies JM, Lewis MP, Wimperis J, et al. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen:prepared on behalf of the British Committee for Standards in Haematology by a Working Party of the Haemato-Oncology Task Force[J]. Br J Haematol, 2011, 155(3):308-317.
[18]
Emmenegger U, Spaeth PJ, Neftel KA. Intravenous immunoglobulin for hemophagocytic lymphohistiocytosis?[J]. J Clin Oncol, 2002, 20(2):599-601.
[19]
Freeman B, Rathore MH, Salman E, et al. Intravenously administered immune globulin for the treatment of infection-associated hemophagocytic syndrome[J]. J Pediatr, 1993, 123(3):479-481.
[20]
Argyraki CK, Gabeta S, Zachou K, et al. Favourable outcome of life-threatening infectious-related haemophagocytic syndrome after combination treatment with corticosteroids and intravenous immunoglobulin infusions[J]. Eur J Intern Med, 2011, 22(6):e155-e157.
[21]
Rajajee S, Ashok I, Manwani N, et al. Profile of hemophagocytic lymphohistiocytosis; efficacy of intravenous immunoglobulin therapy[J]. Indian J Pediatr, 2014, 81(12):1337-1341.
[22]
Zwiers C, Scheffer-Rath ME, Lopriore E, et al. Immunoglobulin for alloimmune hemolytic disease in neonates[J]. Cochrane Database Syst Rev, 2018, 3(3):CD003313.
[23]
Ohto H, Yasuda H, Maeda H, et al. Post-transfusion thrombocytopenia in recipients with anti-HLA antibody[J]. Transfus Sci, 2000, 23(3):271-273.
Mueller-Eckhardt C, Kiefel V. High-dose IgG for post-transfusion purpura-revisited[J]. Blut, 1988, 57(4):163-167.
[26]
Becker T, Panzer S, Maas D, et al. High-dose intravenous immunoglobulin for post-transfusion purpura[J]. Br J Haematol, 1985, 61(1):149-155.
[27]
Sullivan KM, Kopecky KJ, Jocom J, et al. Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation[J]. N Engl J Med, 1990, 323(11):705-712.
[28]
Tiede A, Collins P, Knoebl P, et al. International recommen-dations on the diagnosis and treatment of acquired hemophilia A[J]. Haematologica, 2020, 105(7):1791-1801.
[29]
Sultan Y, Kazatchkine MD, Maisonneuve P, et al. Anti-idiotypic suppression of autoantibodies to factor VⅢ (antihaemophilic factor) by high-dose intravenous gammaglobulin[J]. Lancet, 1984, 2(8406):765-768.
[30]
Franchini M, Lippi G. Acquired factor VⅢ inhibitors[J]. Blood, 2008, 112(2):250-255.
[31]
Lucas M, Lee M, Lortan J, et al. Infection outcomes in patients with common variable immunodeficiency disorders:relationship to immunoglobulin therapy over 22 years[J]. J Allergy Clin Immunol, 2010, 125(6):1354-1360.e4.
[32]
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies)[J]. Clin Immunol, 1999, 93(3):190-197.
[33]
Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogamma-globulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections[J]. Clin Lymphoma Myeloma Leuk, 2013, 13(2):106-111.
[34]
Storek J, Geddes M, Khan F, et al. Reconstitution of the immune system after hematopoietic stem cell transplantation in humans[J]. Semin Immunopathol, 2008, 30(4):425-437.
[35]
Center for International Blood and Marrow Transplant Research (CIBMTR), National Marrow Donor Program (NMDP), European Blood and Marrow Transplant Group (EBMT), et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients:a global perspective[J]. Bone Marrow Transplant, 2009, 44(8):453-558.
[36]
Cowan J, Cameron DW, Knoll G, et al. Protocol for updating a systematic review of randomised controlled trials on the prophylactic use of intravenous immunoglobulin for patients undergoing haematopoietic stem cell transplantation[J]. BMJ Open, 2015, 5(8):e008316.
Christou EAA, Giardino G, Worth A, et al. Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab[J]. Int Rev Immunol, 2017, 36(6):352-359.
[39]
Makatsori M, Kiani-Alikhan S, Manson AL, et al. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes[J]. QJM, 2014, 107(10):821-828.
[40]
Ahmed AR, Kaveri S. Reversing autoimmunity combination of rituximab and intravenous immunoglobulin[J]. Front Immunol, 2018, 9:1189.
[41]
Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia[J]. N Engl J Med, 2011, 365(8):725-733.
[42]
Hill JA, Giralt S, Torgerson TR, et al. CAR-T-and a side order of IgG, to go?-Immunoglobulin replacement in patients receiving CAR-T cell therapy[J]. Blood Rev, 2019, 38:100596.
[43]
Park JH, Romero FA, Taur Y, et al. Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells[J]. Clin Infect Dis, 2018, 67(4):533-540.
[44]
Kansagra AJ, Frey NV, Bar M, et al. Clinical utilization of chimeric antigen receptor T cells in B cell acute lymphoblastic leukemia:an expert opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation[J]. Biol Blood Marrow Transplant, 2019, 25(3):e76-e85.
[45]
van Tilburg CM, Bierings MB, Berbers GA, et al. Impact of treatment reduction for childhood acute lymphoblastic leukemia on serum immunoglobulins and antibodies against vaccine-preventable diseases[J]. Pediatr Blood Cancer, 2012, 58(5):701-707.
[46]
Oscier D, Dearden C, Eren E, et al. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia[J]. Br J Haematol, 2012, 159(5):541-564.
[47]
Cantoni N, Hirsch HH, Khanna N, et al. Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease[J]. Biol Blood Marrow Transplant, 2010, 16(9):1309-1314.
[48]
Chan ST, Logan AC. The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation:why the quest for meaningful prophylaxis still matters[J]. Blood Rev, 2017, 31(3):173-183.
[49]
Schmidt GM, Kovacs A, Zaia JA, et al. Ganciclovir/immunoglobulin combination therapy for the treatment of human cytomegalovirus-associated interstitial pneumonia in bone marrow allograft recipients[J]. Transplantation, 1988, 46(6):905-907.
[50]
Emanuel D, Cunningham I, Jules-Elysee K, et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin[J]. Ann Intern Med, 1988, 109(10):777-782.
[51]
Ljungman P, de la Camara R, Robin C, et al. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7)[J]. Lancet Infect Dis, 2019, 19(8):e260-e272.
[52]
Ljungman P, Cordonnier C, Einsele H, et al. Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients:a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious Diseases Working Party of the EBMT[J]. Bone Marrow Transplant, 1998, 21(5):473-476.
[53]
Jain A, Jain P, Kumar A, et al. Incidence and progression of parvovirus B19 infection and molecular changes in circulating B19V strains in children with haematological malignancy:a follow up study[J]. Infect Genet Evol, 2018, 57:177-184.
[54]
Atay D, Akcay A, Erbey F, et al. The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation[J]. Pediatr Transplant, 2018, 22(2):e13109.
[55]
Karrasch M, Schmidt V, Hammer A, et al. Chronic persistent parvovirus B19 bone marrow infection resulting in transfusion-dependent pure red cell aplasia in multiple myeloma after allogeneic haematopoietic stem cell transplantation and severe graft versus host disease[J]. Hematology, 2017, 22(2):93-98.
[56]
Crabol Y, Terrier B, Rozenberg F, et al. Intravenous immunoglobulin therapy for pure red cell aplasia related to human parvovirus B19 infection:a retrospective study of 10 patients and review of the literature[J]. Clin Infect Dis, 2013, 56(7):968-977.
[57]
Eid AJ, Ardura MI; AST Infectious Diseases Community of Practice. Human parvovirus B19 in solid organ transplantation:guidelines from the American society of transplantation infectious diseases community of practice[J]. Clin Transplant, 2019, 33(9):e13535.
[58]
Stiehm ER. Adverse effects of human immunoglobulin therapy[J]. Transfus Med Rev, 2013, 27(3):171-178.
[59]
Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease:a review of evidence[J]. J Allergy Clin Immunol, 2017, 139(3S):S1-S46.
[60]
Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency[J]. Immunol Allergy Clin North Am, 2008, 28(2):413-437.
[61]
Abolhassani H, Asgardoon MH, Rezaei N, et al. Different brands of intravenous immunoglobulin for primary immunodeficiencies:how to choose the best option for the patient?[J]. Expert Rev Clin Immunol, 2015, 11(11):1229-1243.
[62]
Cherin P, Marie I, Michallet M, et al. Management of adverse events in the treatment of patients with immunoglobulin therapy:a review of evidence[J]. Autoimmun Rev, 2016, 15(1):71-81.
[63]
Finkel AG, Howard JF Jr, Mann JD. Successful treatment of headache related to intravenous immunoglobulin with antimigraine medications[J]. Headache, 1998, 38(4):317-321.
[64]
Matsuda M, Hosoda W, Sekijima Y, et al. Neutropenia as a complication of high-dose intravenous immunoglobulin therapy in adult patients with neuroimmunologic disorders[J]. Clin Neuropharmacol, 2003, 26(6):306-311.
Rachid R, Bonilla FA. The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients:a comprehensive review of the literature[J]. J Allergy Clin Immunol, 2012, 129(3):628-634.
[67]
Eibl MM. History of immunoglobulin replacement[J]. Immunol Allergy Clin North Am, 2008, 28(4):737-764.
[68]
Daniel GW, Menis M, Sridhar G, et al. Immune globulins and thrombotic adverse events as recorded in a large administrative database in 2008 through 2010[J]. Transfusion, 2012, 52(10):2113-2121.
[69]
Ramírez E, Romero-Garrido JA, López-Granados E, et al. Symptomatic thromboembolic events in patients treated with intravenous-immunoglobulins:results from a retrospective cohort study[J]. Thromb Res, 2014, 133(6):1045-1051.
[70]
Rajabally YA, Kearney DA. Thromboembolic complications of intravenous immunoglobulin therapy in patients with neuropathy:a two-year study[J]. J Neurol Sci, 2011, 308(1-2):124-127.
