High infection rates and risk-adapted prevention strategies in contemporary pediatric allogeneic hematopoietic stem cell transplantation

Tsz Wing Yeung , Wilson Yau Ki Chan , Sally Cheuk Ying Wong , Pamela Pui Wah Lee , Daniel Ka Leung Cheuk , Wing Leung

Pediatric Discovery ›› 2024, Vol. 2 ›› Issue (4) : e101

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Pediatric Discovery ›› 2024, Vol. 2 ›› Issue (4) :e101 DOI: 10.1002/pdi3.101
RESEARCH ARTICLE

High infection rates and risk-adapted prevention strategies in contemporary pediatric allogeneic hematopoietic stem cell transplantation

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Abstract

With recent changes in hematopoietic stem cell transplantation (HSCT) practices, such as the increasing use of alternative donors and ex vivo T-cell depletion, how various risk factors interplay and affect the timeline of infections have not been well elucidated. We retrospectively reviewed the first 100 consecutive HSCT from April 2019 to October 2021 in the only pediatric HSCT center in Hong Kong. We found that the vast majority of the allogeneic transplant recipients (69/74, 93.2%) had infections after HSCT, amongst which bacterial, viral, and fungal infection rates were 35.1%, 90.5%, and 9.5%, respectively. In contrast, only 30.8% (8/26) of autologous transplant recipients had infections (rate of bacterial, viral, and fungal infection were 19.2%, 15.4%, and 3.8%, respectively). Human herpesvirus 6 (HHV-6) and BK virus (BKV) typically occurred early after HSCT, adenovirus (ADV) and varicella zoster virus (VZV) thereafter, and cytomegalovirus (CMV) and Epstein–Barr virus (EBV) throughout the entire 2.5-year observation period. Ex vivo T-cell depletion was a general risk factor for viral infection with HHV-6 (hazard ratio [HR] = 3.03), BKV (HR = 3.36), CMV (HR = 4.45), and EBV (HR = 7.15); all p < 0.02. Cancer in second-complete remission compared with firstcomplete remission was a risk factor for bacterial infection (OR = 6.0, 95% CI = 1.12–32.2, and p = 0.037). Patients with gut graft-versus-host disease were at risk for fungal infections (OR = 12.3, 95% CI = 1.33–114.4, and p = 0.027). The infection-related mortality rate was 10.0%, which occurred only in allogeneic HSCT patients with hematological malignancies receiving cord blood (n = 4) or haploidentical HSCT (n = 6). Collectively, our findings in pediatric patients after contemporary HSCT support both time-dependent and risk-adapted measures against infective complications to improve transplant outcome.

Keywords

bacterial infections / hematopoietic stem cell transplantation / invasive fungal diseases / pediatric / viral infections

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Tsz Wing Yeung, Wilson Yau Ki Chan, Sally Cheuk Ying Wong, Pamela Pui Wah Lee, Daniel Ka Leung Cheuk, Wing Leung. High infection rates and risk-adapted prevention strategies in contemporary pediatric allogeneic hematopoietic stem cell transplantation. Pediatric Discovery, 2024, 2(4): e101 DOI:10.1002/pdi3.101

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References

[1]

StyczynskiJ, Czyzewski K, WysockiM, et al. Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study. Clin Microbiol Infect. 2016; 22(2):179.e1-179.e10.

[2]

PhelanR, AroraM, ChenM. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR US summary slides, 2020. Center for Internation Blood and Marrow Transplantaion Research. Accessed February 2022. https://cibmtr.org/CIBMTR/Resources/Summary-Slides-Reports

[3]

IfversenM, MeiselR, SedlacekP, et al. Supportive care during pediatric hematopoietic stem cell transplantation: prevention of infections. A report from workshops on supportive care of the paediatric diseases working party (PDWP) of the European society for blood and marrow transplantation (EBMT). Front Pediatr. 2021; 9:705179.

[4]

TomblynM, Chiller T, EinseleH, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15(10):1143-1238.

[5]

LehrnbecherT, FisherBT, PhillipsB, et al. Guideline for antibacterial prophylaxis administration in pediatric cancer and hematopoietic stem cell transplantation. Clin Infect Dis. 2020; 71(1):226-236.

[6]

LehrnbecherT, Averbuch D, CastagnolaE, et al. 8th European Conference on Infections in Leukaemia:2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol. 2021; 22(6): e270-e280.

[7]

GrollAH, PanaD, LanternierF, et al. 8th European Conference on Infections in Leukaemia:2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol. 2021; 22(6): e254-e269.

[8]

FalconCP, Broglie L, PhelanR, ChoiSW, Auletta JJ, ChewningJH. Infection prophylaxis patterns following pediatric autologous hematopoietic stem cell transplantation: a survey of Pediatric Transplant and Cell Therapy Consortium centers. Pediatr Transplant. 2020; 24(8):e13821.

[9]

Caldas TeixeiraD, Martins OliveiraDL, Orlandi Mourão PH, et al. Infection surveillance in pediatric hematopoietic stem cell transplantation recipients. Eur J Haematol. 2018; 100(1):69-74.

[10]

BenjaminDKJ, MillerWC, BayliffS, Martel L, AlexanderKA, MartinPL. Infections diagnosed in the first year after pediatric stem cell transplantation. Pediatr Infect Dis J. 2002; 21(3):227-234.

[11]

SrinivasanA, WangC, SrivastavaDK, et al. Timeline, epidemiology, and risk factors for bacterial, fungal, and viral infections in children and adolescents after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013; 19(1):94-101.

[12]

ZinterMS, LevyER, GertzSJ. A review of pathogens causing lower respiratory tract infection in the pediatric hematopoietic stem cell transplant recipient. J Pediatr Intensive Care. 2014; 3(3):115-132.

[13]

DandoyCE, KelleyT, GaurAH, et al. Outcomes after bloodstream infection in hospitalized pediatric hematology/oncology and stem cell transplant patients. Pediatr Blood Cancer. 2019; 66(12):e27978.

[14]

DüverF, Weißbrich B, EyrichM, WölflM, Schlegel PG, WiegeringV. Viral reactivations following hematopoietic stem cell transplantation in pediatric patients – a single center 11-year analysis. PLoS One. 2020; 15(2):e0228451.

[15]

CzyzewskiK, Dziedzic M, SalamonowiczM, et al. Epidemiology, outcome and risk factors analysis of viral infections in children and adolescents undergoing hematopoietic cell transplantation: antiviral drugs do not prevent Epstein-Barr virus reactivation. Infect Drug Resist. 2019; 12:3893-3902.

[16]

AtayD, AkcayA, ErbeyF, Ozturk G. The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation. Pediatr Transplant. 2018; 22(2):e13109.

[17]

DvorakCC, Steinbach WJ, BrownJMY, AgarwalR. Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2005; 36(7):621-629.

[18]

HolJA, WolfsTFW, BieringsMB, et al. Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients. Bone Marrow Transplant. 2014; 49(1):95-101.

[19]

SrinivasanA, McLaughlin L, WangC, et al. Early infections after autologous hematopoietic stem cell transplantation in children and adolescents: the St. Jude experience. Transpl Infect Dis. 2014; 16(1):90-97.

[20]

BallenK, AhnKW, ChenM, et al. Infection rates among acute leukemia patients receiving alternative donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016; 22(9):1636-1645.

[21]

Zając-SpychałaO, Zaucha-PrażmoA, Zawitkowska J, et al. Infectious complications after hematopoietic stem cell transplantation for primary immunodeficiency in children: a multicenter nationwide study. Pediatr Allergy Immunol. 2020; 31(5):537-543.

[22]

Zaucha-PrażmoA, Zawitkowska J, LejmanM, et al. Infection profile in children and adolescents with bone marrow failures treated with allogeneic hematopoietic stem cell transplantation. Pediatr Transplant. 2019; 23(8):e13592.

[23]

PichlerH, Lawitschka A, GlogovaE, et al. Allogeneic hematopoietic stem cell transplantation from unrelated donors is associated with higher infection rates in children with acute lymphoblastic leukemia-a prospective international multicenter trial on behalf of the BFM-SG and the EBMT-PDWP. Am J Hematol. 2019; 94(8):880-890.

[24]

LibbrechtC, Goutagny MP, BacchettaJ, et al. Impact of a change in protected environment on the occurrence of severe bacterial and fungal infections in children undergoing hematopoietic stem cell transplantation. Eur J Haematol. 2016; 97(1):70-77.

[25]

KjellinM, Qudeimat A, BrowneE, et al. Effectiveness of bath wipes after hematopoietic cell transplantation: a randomized trial. J Pediatr Oncol Nurs. 2020; 37(6):390-397.

[26]

LindsayJ, Kerridge I, WilcoxL, et al. Infection-related mortality in adults and children undergoing allogeneic hematopoietic cell transplantation: an Australian registry report. Transplant Cell Ther. 2021; 27(9):798.e1-798.e10.

[27]

BariR, Rujkijyanont P, SullivanE, et al. Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2013; 31(30):3782-3790.

[28]

PrzepiorkaD, Weisdorf D, MartinP, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995; 15(6):825-828.

[29]

JagasiaMH, Greinix HT, AroraM, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015; 21(3):389-401.e1.

[30]

DonnellyJP, ChenSC, KauffmanCA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020; 71(6):1367-1376.

[31]

StyczyńskiJ, Tridello G, KosterL, et al. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020; 55(1):126-136.

[32]

YoshifujiK, Inamoto K, KiridoshiY, et al. Prebiotics protect against acute graft-versus-host disease and preserve the gut microbiota in stem cell transplantation. Blood Adv. 2020; 4(19):4607-4617.

[33]

ShonoY, van den Brink MRM. Gut microbiota injury in allogeneic haematopoietic stem cell transplantation. Nat Rev Cancer. 2018; 18(5):283-295.

[34]

SchwabkeyZI, JenqRR. Microbiome anomalies in allogeneic hematopoietic cell transplantation. Annu Rev Med. 2020; 71(1):137-148.

[35]

TriplettBM, MullerB, KangG-L, et al. Selective T-cell depletion targeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion. Transpl Infect Dis. 2018; 20(1):10.

[36]

LorentinoF, XueE, MastaglioS, et al. Letermovir reduces chronic GVHD risk in calcineurin inhibitor-free GVHD prophylaxis after hematopoietic cell transplantation. Blood Adv. 2022; 6(10):3053-3057.

[37]

ChuleeraruxN, Nematollahi S, ThongkamA, et al. The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis. Clin Microbiol Infect. 2022; 28(3):332-344.

[38]

ChoeH, Ferrara JLM. New therapeutic targets and biomarkers for acute graft-versus-host disease (GVHD). Expert Opin Ther Targets. 2021; 25(9):761-771.

[39]

MenzinJ, MeyersJL, FriedmanM, et al. The economic costs to United States hospitals of invasive fungal infections in transplant patients. Am J Infect Control. 2011; 39(4): e15-e20.

[40]

El HaddadL, Ghantoji SS, ParkAK, et al. Clinical and economic burden of pre-emptive therapy of cytomegalovirus infection in hospitalized allogeneic hematopoietic cell transplant recipients. J Med Virol. 2020; 92(1):86-95.

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2024 The Author(s). Pediatric Discovery published by John Wiley & Sons Australia, Ltd on behalf of Children’s Hospital of Chongqing Medical University.

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