Междисциплинарный подход к ведению онкогематологических пациентов с иммунодефицитом на примере клинических случаев

Бабичева Л.Г., Лунцов А.В., Хусаинова Г.Н., Поддубная И.В. Междисциплинарный подход к ведению онкогематологических пациентов с иммунодефицитом на примере клинических случаев. Современная Онкология. 2023;25(3):365–372. DOI: 10.26442/18151434.2023.3.202446

© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.

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Babicheva LG, Luntsov AV, Khusainova GN, Poddubnaya IV. An interdisciplinary approach to the management of oncohematological patients with immunodeficiency: clinical cases. A review. Journal of Modern Oncology. 2023;25(3):365–372. DOI: 10.26442/18151434.2023.3.202446

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Аннотация

Иммунодефицит возникает, когда один или несколько компонентов иммунной системы не функционируют должным образом, вследствие чего организм теряет способность противостоять в первую очередь инфекционным агентам. Большинство случаев иммунодефицита у взрослых являются приобретенными (вторичными), однако нередки и врожденные дефекты иммунитета. Первичные иммунодефициты – это гетерогенная группа врожденных ошибок иммунитета, которые приводят к различным клиническим и лабораторным проявлениям. Напротив, вторичные иммунодефициты – это приобретенное снижение количества иммунных клеток и/или нарушение их функции, что чаще всего характеризуется снижением уровня антител. Вторичный иммунодефицит у пациентов с В-клеточными гематологическими злокачественными новообразованиями является распространенным состоянием, которое может быть обусловлено как самим гемобластозом, так и вторичными, связанными с противоопухолевой терапией причинами. Как это ни парадоксально, иммунодефицит, первоначально приписываемый вторичным причинам, может быть обусловлен не диагностированным ранее первичным иммунодефицитом. Ранняя диагностика иммунодефицита и оптимизация стратегий ведения пациента с мультидисциплинарным подходом являются ключом к обеспечению наиболее эффективных методов специфического лечения, а также снижению частоты осложнений и смертности, связанных с инфекцией. В статье обсуждаются клиническая практика, рекомендации и проблемы диагностики иммунодефицита, а также эффективность заместительной терапии иммуноглобулинами на примере клинических случаев.

Ключевые слова: первичный иммунодефицит, вторичный иммунодефицит, иммуноглобулины, Привиджен, В-клеточные лимфопролиферативные заболевания, инфекционные осложнения, лимфома, множественная миелома, хронический лимфолейкоз

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Immunodeficiency occurs when one or more immune system components do not function properly, resulting in the body's inability to resist mostly infectious agents. Most cases of immunodeficiency in adults are acquired (secondary), but congenital immunodeficiencies are not uncommon. Primary immunodeficiencies are a heterogeneous group of innate immune errors that result in various clinical and laboratory manifestations. In contrast, secondary immunodeficiencies involve an acquired decrease in immune cell count and/or impairment of their function, commonly associated with an antibody level decrease. Secondary immunodeficiency in patients with B-cell hematological malignancies is a common condition attributed to both hematological malignancy and secondary antitumor therapy-related causes. Paradoxically, immunodeficiency, initially attributed to secondary causes, may be due to a previously undiagnosed primary immunodeficiency. Early diagnosis of immunodeficiency and optimization of management strategies with a multidisciplinary approach are critical to providing the most effective specific treatments and reducing the incidence of infection-related complications and mortality. The article addresses clinical practice, recommendations, and problems of immunodeficiency diagnosis and the effectiveness of immunoglobulin replacement therapy illustrated by clinical cases.

Keywords: primary immunodeficiency, secondary immunodeficiency, immunoglobulins, Privigen, B-cell lymphoproliferative diseases, infectious complications, lymphoma, multiple myeloma, chronic lymphocytic leukemia

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Список литературы

1. Chinen J, Shearer WT. Secondary Immunodeficiencies, Including HIV Infection. J Allergy Clin Immunol. 2010;125(2 Suppl. 2):S195-203. DOI:10.1016/j.jaci.2009.08.040
2. 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
3. Sánchez-Ramón S, Bermúdez A, González-Granado LI, et al. Primary and Secondary Immunode΄ ficiency Diseases in Oncohaematology: Warning Signs, Diagnosis, and Management. Front Immunol. 2019;10:586. DOI:10.3389/fimmu.2019.00586
4. Thalhammer J, Kindle G, Nieters A, et al. Initial Presenting Manifestations in 16,486 Patients With Inborn Errors of Immunity Include Infections and Noninfectious Manifestations. J Allergy Clin Immunol. 2021;148(5):1332-41.e5. DOI:10.1016/j.jaci.2021.04.015
5. Mayor PC, Eng KH, Singel KL, et al. Cancer in Primary Immunodeficiency Diseases: Cancer Incidence in the United States Immune Deficiency Network Registry. J Allergy Clin Immunol. 2018;141(3):1028-35. DOI:10.1016/j.jaci.2017.05.024
6. Amaya-Uribe L, Rojas M, Azizi G, et al. Primary Immunodeficiency and Autoimmunity: A Comprehensive Review. J Autoimmun. 2019;99:52-72. DOI:10.1016/j.jaut.2019.01.011
7. Otani IM, Lehman HK, Jongco AM, et al. 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. 2020;149(5):1525-60.
8. Kiaee F, Azizi G, Rafiemanesh H, et al. Malignancy in Common Variable Immunodeficiency: A Systematic Review and Meta-Analysis. Expert Rev Clin Immunol. 2019;15(10):1105-13. DOI:10.1080/1744666X.2019.1658523
9. Kralickova P, Milota T, Litzman J, et al. CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID. Front Immunol. 2019;9:3135. DOI:10.3389/fimmu.2018.03135
10. Salavoura K, Kolialexi A, Tsangaris G, Mavrou A. Development of Cancer in Patients With Primary Immunodeficiencies. Anticancer Res. 2008;28(2B):1263-9.
11. Vacca A, Melaccio A, Sportelli A, et al. Subcutaneous immunoglobulins in patients with multiple myeloma and secondary hypogammaglobulinemia: a randomized trial. Clin Immunol. 2018;91:110-5.
12. Wehr C, Houet L, Unger S, et al. Altered Spectrum of Lymphoid Neoplasms in a Single-Center Cohort of Common Variable Immunodeficiency With Immune Dysregulation. J Clin Immunol. 2021;41(6):1250-65. DOI:10.1007/s10875-021-01016-4
13. Shah N, Mustafa SS, Vinh DC. Management of secondary immunodeficiency in hematological malignancies in the era of modern oncology. Crit Rev Oncol Hematol. 2023;181. DOI:10.1016/j.critrevonc.2022.103896
14. Jolles S, Michallet M, Agostini C, et al. Treating secondary antibody deficiency in patients with haematological malignancy: European expert consensus. Eur J Haematol. 2021;106(4):439-49.
15. Jolles S, Giralt S, Kerre T, et al. Secondary antibody deficiency in chronic lymphocytic leukemia and nonHodgkin lymphoma: Recommendations from an international expert panel. Blood Rev. 2022;101020.
16. Colovic NBA, Martinovic-Cemerikic V, Jankovic G. Prognostic significance of serum immunoglobulins in B-chronic lymphocytic leukemia. Arch Oncol. 2021;9:79-82.
17. Gardulf A, Nicolay U, Math D, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol. 2004;114:936-42.
18. Gardulf A, Borte M, Ochs HD, Nicolay U. Prognostic factors for health-related quality of life in adults and children with primary antibody deficiencies receiving SCIG home therapy. Clin Immunol. 2008;126:81-8
19. Nicolay U, Kiessling P, Berger M, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol. 2006;26:65-72.
20. Gardulf A, Nicolay U. Replacement IgG therapy and self-therapy at home improve the health-related quality of life in patients with primary antibody deficiencies. Curr Opin Allergy Clin Immunol. 2006;6:434-42.
21. Gardulf A, Bjorvell H, Gustafson R, et al. The life situations of patients with primary antibody deficiency untreated or treated with subcutaneous gammaglobulin infusions. Clin Exp Immunol. 1993;92:200-4.
22. Lingman-Framme J, Fasth A. Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: an evidence-based review. Drugs. 2013;73:1307‑19.
23. Fasth A, Nystrom J. Quality of life and health-care resource utilization among children with primary immunodeficiency receiving home treatment with subcutaneous human immunoglobulin. J Clin Immunol. 2008;28:370-8.
24. Haddad E, Barnes D, Kafal A. Home therapy with subcutaneous immunoglobulins for patients with primary immunodeficiency diseases. Transfus Apher Sci. 2012; 46:315-21.
25. Legendre P, Chahwan D, Marjanovic Z, et al. 2020. Utilization of intravenous or subcutaneous immunoglobulins in secondary immune deficiency (ULTIMATE): a retrospective multicenter study. Clin Immunol. 2020;215:108419.
26. Blimark C, Holmberg E, Mellqvist UH, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015;100(1):107-13.
27. Perri RT, Hebbel RP, Oken MM. Influence of treatment and response status on infection risk in multiple myeloma. Am J Med. 1981;71(6):935-40.
28. Compagno N, Malipiero G, Cinetto F, Agostini C. Immunoglobulin replacement therapy in secondary hypogammaglobulinemia. Front Immunol. 2014;5:626.
29. Spadaro G, Pecoraro A, De Renzo A, et al. Intravenous versus subcutaneous immunoglobulin replacement in secondary hypogammaglobulinemia. Clin Immunol. 2016;166-167:103-4.
30. Srivastava S, Wood P. Secondary antibody deficiency – causes and approach to diagnosis. Clin Med. 2016;16(6):571-6.
31. Mustafa SS, Jamshed S, Vadamalai K, Ramsey A. The use of 20 % subcutaneous immunoglobulin replacement therapy in patients with B cell nonHodgkin lymphoma with humoral immune dysfunction after treatment with rituximab. Clin Lymphoma Myeloma Leuk. 2020;20(9):e590-6.
32. Kochenderfer JN, Wilson WH, Janik JE, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116(20):4099-102.
33. Porter DL, Hwang WT, Frey N, et al. 2015. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.
34. Поддубная И.В., Бабичева Л.Г. Сопроводительная терапия онкогематологических пациентов при вторичных иммунодефицитах. Современная Oнкология.
2020;22(2):119-26 [Poddubnaya IV, Babicheva LG. Accompanying therapy in oncohematological patients with secondary immunodeficiency. Journal of Modern Oncology.
2020;22(2):89-97 (in Russian)].
35. Yakaboski E, Fuleihan RL, Sullivan KE, et al. Lymphoproliferative Disease in CVID: a Report of Types and Frequencies from a US Patient Registry. J Clin Immunol. 2020;40(3):524-30. DOI:10.1007/s10875-020-00769-8
36. Ameratunga R, Lehnert K, Woon ST, et al. Review: Diagnosing Common Variable Immunodeficiency Disorder in the Era of Genome Sequencing. Clin Rev Allergy Immunol. 2018;54(2):261-8. DOI:10.1007/s12016-017-8645-0

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1. Chinen J, Shearer WT. Secondary Immunodeficiencies, Including HIV Infection. J Allergy Clin Immunol. 2010;125(2 Suppl. 2):S195-203. DOI:10.1016/j.jaci.2009.08.040
2. 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
3. Sánchez-Ramón S, Bermúdez A, González-Granado LI, et al. Primary and Secondary Immunode΄ ficiency Diseases in Oncohaematology: Warning Signs, Diagnosis, and Management. Front Immunol. 2019;10:586. DOI:10.3389/fimmu.2019.00586
4. Thalhammer J, Kindle G, Nieters A, et al. Initial Presenting Manifestations in 16,486 Patients With Inborn Errors of Immunity Include Infections and Noninfectious Manifestations. J Allergy Clin Immunol. 2021;148(5):1332-41.e5. DOI:10.1016/j.jaci.2021.04.015
5. Mayor PC, Eng KH, Singel KL, et al. Cancer in Primary Immunodeficiency Diseases: Cancer Incidence in the United States Immune Deficiency Network Registry. J Allergy Clin Immunol. 2018;141(3):1028-35. DOI:10.1016/j.jaci.2017.05.024
6. Amaya-Uribe L, Rojas M, Azizi G, et al. Primary Immunodeficiency and Autoimmunity: A Comprehensive Review. J Autoimmun. 2019;99:52-72. DOI:10.1016/j.jaut.2019.01.011
7. Otani IM, Lehman HK, Jongco AM, et al. 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. 2020;149(5):1525-60.
8. Kiaee F, Azizi G, Rafiemanesh H, et al. Malignancy in Common Variable Immunodeficiency: A Systematic Review and Meta-Analysis. Expert Rev Clin Immunol. 2019;15(10):1105-13. DOI:10.1080/1744666X.2019.1658523
9. Kralickova P, Milota T, Litzman J, et al. CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID. Front Immunol. 2019;9:3135. DOI:10.3389/fimmu.2018.03135
10. Salavoura K, Kolialexi A, Tsangaris G, Mavrou A. Development of Cancer in Patients With Primary Immunodeficiencies. Anticancer Res. 2008;28(2B):1263-9.
11. Vacca A, Melaccio A, Sportelli A, et al. Subcutaneous immunoglobulins in patients with multiple myeloma and secondary hypogammaglobulinemia: a randomized trial. Clin Immunol. 2018;91:110-5.
12. Wehr C, Houet L, Unger S, et al. Altered Spectrum of Lymphoid Neoplasms in a Single-Center Cohort of Common Variable Immunodeficiency With Immune Dysregulation. J Clin Immunol. 2021;41(6):1250-65. DOI:10.1007/s10875-021-01016-4
13. Shah N, Mustafa SS, Vinh DC. Management of secondary immunodeficiency in hematological malignancies in the era of modern oncology. Crit Rev Oncol Hematol. 2023;181. DOI:10.1016/j.critrevonc.2022.103896
14. Jolles S, Michallet M, Agostini C, et al. Treating secondary antibody deficiency in patients with haematological malignancy: European expert consensus. Eur J Haematol. 2021;106(4):439-49.
15. Jolles S, Giralt S, Kerre T, et al. Secondary antibody deficiency in chronic lymphocytic leukemia and nonHodgkin lymphoma: Recommendations from an international expert panel. Blood Rev. 2022;101020.
16. Colovic NBA, Martinovic-Cemerikic V, Jankovic G. Prognostic significance of serum immunoglobulins in B-chronic lymphocytic leukemia. Arch Oncol. 2021;9:79-82.
17. Gardulf A, Nicolay U, Math D, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol. 2004;114:936-42.
18. Gardulf A, Borte M, Ochs HD, Nicolay U. Prognostic factors for health-related quality of life in adults and children with primary antibody deficiencies receiving SCIG home therapy. Clin Immunol. 2008;126:81-8
19. Nicolay U, Kiessling P, Berger M, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol. 2006;26:65-72.
20. Gardulf A, Nicolay U. Replacement IgG therapy and self-therapy at home improve the health-related quality of life in patients with primary antibody deficiencies. Curr Opin Allergy Clin Immunol. 2006;6:434-42.
21. Gardulf A, Bjorvell H, Gustafson R, et al. The life situations of patients with primary antibody deficiency untreated or treated with subcutaneous gammaglobulin infusions. Clin Exp Immunol. 1993;92:200-4.
22. Lingman-Framme J, Fasth A. Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: an evidence-based review. Drugs. 2013;73:1307‑19.
23. Fasth A, Nystrom J. Quality of life and health-care resource utilization among children with primary immunodeficiency receiving home treatment with subcutaneous human immunoglobulin. J Clin Immunol. 2008;28:370-8.
24. Haddad E, Barnes D, Kafal A. Home therapy with subcutaneous immunoglobulins for patients with primary immunodeficiency diseases. Transfus Apher Sci. 2012; 46:315-21.
25. Legendre P, Chahwan D, Marjanovic Z, et al. 2020. Utilization of intravenous or subcutaneous immunoglobulins in secondary immune deficiency (ULTIMATE): a retrospective multicenter study. Clin Immunol. 2020;215:108419.
26. Blimark C, Holmberg E, Mellqvist UH, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015;100(1):107-13.
27. Perri RT, Hebbel RP, Oken MM. Influence of treatment and response status on infection risk in multiple myeloma. Am J Med. 1981;71(6):935-40.
28. Compagno N, Malipiero G, Cinetto F, Agostini C. Immunoglobulin replacement therapy in secondary hypogammaglobulinemia. Front Immunol. 2014;5:626.
29. Spadaro G, Pecoraro A, De Renzo A, et al. Intravenous versus subcutaneous immunoglobulin replacement in secondary hypogammaglobulinemia. Clin Immunol. 2016;166-167:103-4.
30. Srivastava S, Wood P. Secondary antibody deficiency – causes and approach to diagnosis. Clin Med. 2016;16(6):571-6.
31. Mustafa SS, Jamshed S, Vadamalai K, Ramsey A. The use of 20 % subcutaneous immunoglobulin replacement therapy in patients with B cell nonHodgkin lymphoma with humoral immune dysfunction after treatment with rituximab. Clin Lymphoma Myeloma Leuk. 2020;20(9):e590-6.
32. Kochenderfer JN, Wilson WH, Janik JE, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116(20):4099-102.
33. Porter DL, Hwang WT, Frey N, et al. 2015. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.
34. Poddubnaya IV, Babicheva LG. Accompanying therapy in oncohematological patients with secondary immunodeficiency. Journal of Modern Oncology. 2020;22(2):89-97 (in Russian).
35. Yakaboski E, Fuleihan RL, Sullivan KE, et al. Lymphoproliferative Disease in CVID: a Report of Types and Frequencies from a US Patient Registry. J Clin Immunol. 2020;40(3):524-30. DOI:10.1007/s10875-020-00769-8
36. Ameratunga R, Lehnert K, Woon ST, et al. Review: Diagnosing Common Variable Immunodeficiency Disorder in the Era of Genome Sequencing. Clin Rev Allergy Immunol. 2018;54(2):261-8. DOI:10.1007/s12016-017-8645-0

Авторы

Л.Г. Бабичева*¹, А.В. Лунцов², Г.Н. Хусаинова³, И.В. Поддубная¹

¹ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
²ГАУЗ «Республиканская клиническая больница» Минздрава Республики Татарстан, Казань, Россия;
³ГАУЗ «Республиканский клинический онкологический диспансер им. проф. М.З. Сигала», Казань, Россия
*lalibabicheva@mail.ru

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Lali G. Babicheva*¹, Alexey V. Luntsov², Gulnara N. Khusainova³, Irina V. Poddubnaya¹

¹Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
²Republican Clinical Hospital, Kazan, Russia;
³Sigal Republican Clinical Oncology Dispensary, Kazan, Russia
*lalibabicheva@mail.ru

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