Immune reconstitution inflammatory syndrome in HIV-negative patients with hematological malignancies and hematopoietic stem cell transplantation: A case series and a literature review
DOI:
https://doi.org/10.46765/2675-374X.2025v6n1p253Keywords:
Immune Reconstitution Inflammatory Syndrome, Immunosuppression therapy, Opportunistic infectionsAbstract
Immune reconstitution inflammatory syndrome (IRIS) is a potentially severe complication following the withdrawal of immunosuppressive agents, commonly studied in human immunodeficiency virus (HIV) positive patients. However, its impact on individuals with hematological malignancies and those undergoing hematopoietic stem cell transplants is less understood. This study aimed to establish diagnostic criteria for IRIS in these populations and assess its incidence and clinical progression. A cross-sectional, prospective observational study was conducted with 159 chemotherapy patients and 96 hematopoietic stem cell transplant recipients. IRIS diagnosis criteria were derived from a literature review of 70 studies, and patients were monitored for 11 months. The review identified key IRIS diagnostic criteria, including paradoxical clinical worsening, antimicrobial refractoriness, and inflammatory signs following immunosuppressive therapy. Most IRIS cases were linked to pathogens like Mycobacterium, Candida spp., and Aspergillus spp. Among our patients, three cases of IRIS were identified: one related to the Bacillus Calmette-Guérin (BCG) vaccine, another with neutrophil recovery, and the third with chronic disseminated candidiasis. Treatment with corticosteroids and antimicrobial therapy allowed continued chemotherapy without impacting the underlying disease’s outcomes. IRIS is an important complication in hematological and stem cell transplant patients. Early recognition and appropriate treatment, including corticosteroids and antimicrobial therapy, are critical for successful management and uninterrupted cancer treatment.
References
1. Wong C-S, Richards E, Pei L, Sereti I. Immune reconstitution inflammatory syndrome in HIV infection: taking the bad with the good. Oral Diseases. 2016;23(7):822–7. https://doi.org/10.1111/odi.12606 DOI: https://doi.org/10.1111/odi.12606
2. Thapa S, Shrestha U. Immune reconstitution inflammatory syndrome. PubMed. Treasure Island (FL): StatPearls Publishing; 2022 [cited Aug 18, 2025]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567803/
3. Barretto J, Wirk B. Early recognition of immune reconstitution inflammatory syndrome leads to avoidance of endotracheal intubation. World J Oncol. 2012;3(4):194–8. https://doi.org/10.4021/wjon527w DOI: https://doi.org/10.4021/wjon527w
4. van Lier DP, Janssen NA, Snoeren MM, Verweij PE, Blijlevens NM, van der Velden WJ. Ernstige inflammatie tijdens herstel van neutropenia: het immuunreconstitutie-inflammatoir-syndroom na chemotherapie [Severe inflammation during recovery from neutropenia: the immune reconstitution inflammatory syndrome following chemotherapy]. Ned Tijdschr Geneeskd. 2015;159:A8968. Available at: https://pubmed.ncbi.nlm.nih.gov/26246060/
5. Alawin IA, Karnath BM. Paradoxical immune reconstitution syndrome presenting as acute respiratory distress syndrome in a leukemia patient during neutrophil recovery. Case Rep Hematol. 2012;2012:670347. https://doi.org/10.1155/2012/670347 DOI: https://doi.org/10.1155/2012/670347
6. Bicakci Z, Koca D and Bozbeyoğlu G. Immune reconstitution inflammatory syndrome associated with hepatosplenic candidiasis in a patient with acute myeloblastic leukemia: possible pathogenesis and treatment in the light of current knowledge. Austin Hematol. 2021;6(2):1039. Available at: https://austinpublishinggroup.com/austin-hematology/fulltext/hematol-v6-id1039.php DOI: https://doi.org/10.26420/austinhematol.2021.1039
7. Novak RM, Richardson JT, Buchacz K, Chmiel JS, Durham MD, Palella FJ, et al. Immune reconstitution inflammatory syndrome. AIDS. https://doi.org/10.1097/QAD.0b013e3283511e91 DOI: https://doi.org/10.1097/QAD.0b013e3283511e91
8. Ratnam I, Chiu C, Kandala N-B, Easterbrook PJ. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort. Clin Infect Dis. 2006;42(3): 418–27. https://doi.org/10.1086/499356 DOI: https://doi.org/10.1086/499356
9. Santiago L. Immune reconstitution inflammatory syndrome in HIV-negative patients with hematological malignancies and hematopoietic stem cell transplantation: a case series and a literature review. figshare. Dataset. 2025. https://doi.org/10.6084/m9.figshare.29936858.v1
10. Church LWP, Chopra A, Judson MA. Paradoxical reactions and the immune reconstitution inflammatory syndrome. Microbiol Spectr. 2017;5(2):10.1128/microbiolspec.tnmi7-0033-2016. https://doi.org/10.1128/microbiolspec.tnmi7-0033-2016 DOI: https://doi.org/10.1128/microbiolspec.TNMI7-0033-2016
11. Barber DL, Andrade BB, Sereti I, Sher A. Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol. 2012;10(2):150–6. https://doi.org/10.1038/nrmicro2712 DOI: https://doi.org/10.1038/nrmicro2712
12. Shahani L, Hamill RJ. Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome. Transl Res. 2016;167(1):88–103. https://doi.org/10.1016/j.trsl.2015.07.010 DOI: https://doi.org/10.1016/j.trsl.2015.07.010
13. Sun HY, Singh N. Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients. Curr Opin Infect Dis. 2009;22(4):394–402. https://doi.org/10.1097/QCO.0b013e32832d7aff DOI: https://doi.org/10.1097/QCO.0b013e32832d7aff
14. Sueki H, Mizukawa Y, Aoyama Y. Immune reconstitution inflammatory syndrome in non-HIV immunosuppressed patients. J Dermatol. 2018;45(1):3–9. https://doi.org/10.1111/1346-8138.14074 DOI: https://doi.org/10.1111/1346-8138.14074
15. Breton G. Syndrome inflammatoire de reconstitution immune. Médecine/Sciences. 2010;26(3):281–90. https://doi.org/10.1051/medsci/2010263281 DOI: https://doi.org/10.1051/medsci/2010263281
16. Jung J, Hong HL, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Immune reconstitution inflammatory syndrome in neutropenic patients with invasive pulmonary aspergillosis. J Infect. 2015;70(6):659–67. https://doi.org/10.1016/j.jinf.2014.12.020 DOI: https://doi.org/10.1016/j.jinf.2014.12.020
17. Singh N, Lortholary O, Alexander BD, Gupta KL, John GT, Pursell K, Munoz P, Klintmalm GB, Stosor V, delBusto R, Limaye AP, Somani J, Lyon M, Houston S, House AA, Pruett TL, Orloff S, Humar A, Dowdy L, Garcia-Diaz J, Fisher RA, Husain S; Cryptococcal Collaborative Transplant Study Group. Allograft loss in renal transplant recipients with cryptococcus neoformans associated immune reconstitution syndrome. Transplantation. 2005;80(8):1131–3. https://doi.org/10.1097/01.tp.0000180530.17683.02 DOI: https://doi.org/10.1097/01.tp.0000180530.17683.02
18. Dhamija E, Meena P, Ramalingam V, Sahoo R, Rastogi S, Thulkar S. Chemotherapy-induced pulmonary complications in cancer: Significance of clinicoradiological correlation. Indian J Radiol Imaging. 2020;30(1):20–6. https://doi.org/10.4103/ijri.IJRI_178_19 DOI: https://doi.org/10.4103/ijri.IJRI_178_19
19. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50(3):291–322. https://doi.org/10.1086/649858 DOI: https://doi.org/10.1086/649858
20. Miceli MH, Maertens J, Buvé K, Grazziutti M, Woods G, Rahman M, Barlogie B, Anaissie EJ. Immune reconstitution inflammatory syndrome in cancer patients with pulmonary aspergillosis recovering from neutropenia: Proof of principle, description, and clinical and research implications. Cancer. 2007;110(1):112–20. https://doi.org/10.1002/cncr.22738 DOI: https://doi.org/10.1002/cncr.22738
21. Meintjes G, Wilkinson RJ, Morroni C, Pepper DJ, Rebe K, Rangaka MX, Oni T, Maartens G. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS. 2010;24(15):2381–90. https://doi.org/10.1097/QAD.0b013e32833dfc68 DOI: https://doi.org/10.1097/QAD.0b013e32833dfc68
22. Mahomed N, Reubenson G. Immune reconstitution inflammatory syndrome in children. SA J Radiol. 2017;21(2):1257. https://doi.org/10.4102/sajr.v21i2.1257 DOI: https://doi.org/10.4102/sajr.v21i2.1257
23. Mosleh S, Rabaia D, Zidan T. Successful treatment of chronic disseminated candidiasis complicated by immune reconstitution inflammatory syndrome in a child with acute lymphocytic leukemia. Cureus. 2023;15(8):e44103. https://doi.org/10.7759/cureus.44103 DOI: https://doi.org/10.7759/cureus.44103
24. Liu S, Huo F, Dai G, Wu J, Qin M, Mao H, Wang Q. Case Report: Immune reconstitution inflammatory syndrome after hematopoietic stem cell transplantation for severe combined immunodeficiency. Front Immunol. 2022;13:960749. https://doi.org/10.3389/fimmu.2022.960749 DOI: https://doi.org/10.3389/fimmu.2022.960749
25. Arora S, Rastogi N, Upasana K, Yadav A, Thakkar D, Satya Prakash Y. Cytokine release syndrome with immune reconstitution inflammatory syndrome post haploidentical hematopoietic stem cell transplantation in a child with severe combined immunodeficiency and disseminated BCG infection. J Pediatr Hematol Oncol. 2022;7(4):S26. https://doi.org/10.1016/j.phoj.2022.10.072 DOI: https://doi.org/10.1016/j.phoj.2022.10.072
26. Corbali O, Gemici Karaaslan HB, Aydemir S, Onal P, Kendir Demirkol Y, Nepesov S, Kiykim A, Cokugras H. Immune reconstitution inflammatory syndrome after hematopoietic stem cell transplantation in a FOXN1-deficient patient. J Pediatr Hematol Oncol. 2023;45(5):275–7. https://doi.org/10.1097/MPH.0000000000002677 DOI: https://doi.org/10.1097/MPH.0000000000002677
27. Candon S, Rammaert B, Foray AP, Moreira B, Gallego Hernanz MP, Chatenoud L, Lortholary O. Chronic disseminated candidiasis during hematological malignancies: an immune reconstitution inflammatory syndrome with expansion of pathogen-specific T helper type 1 cells. J Infect Dis. 2020;221(11):1907–16. https://doi.org/10.1093/infdis/jiz688 DOI: https://doi.org/10.1093/infdis/jiz688
28. Reddy NA, Addala S, Lashkari HP. Subcutaneous microabscesses and myositis as part of immune reconstitution inflammatory syndrome due to chronic disseminated candidiasis in a child with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2023;45(4):e555–9. https://doi.org/10.1097/ MPH.0000000000002640 DOI: https://doi.org/10.1097/MPH.0000000000002640
29. Al Yazidi LS, Elsidig N, Wali Y, Nazir H. Chronic disseminated candidiasis in children and the role of corticosteroids therapy. Pediatr Infect Dis J. 2023;42(5):e146–e151. https://doi.org/10.1097/ INF.0000000000003859 DOI: https://doi.org/10.1097/INF.0000000000003859
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY
This work is licensed under a Creative Commons Attribution 4.0 International License.
