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Review
. 2020 Sep 16:10:581447.
doi: 10.3389/fonc.2020.581447. eCollection 2020.

How We Treat Fever and Hypotension in Pediatric Hematopoietic Cell Transplant Patients

Matt S Zinter  1 , Christopher C Dvorak  2 , Jeffery J Auletta  3   4
Affiliations
Review

How We Treat Fever and Hypotension in Pediatric Hematopoietic Cell Transplant Patients

Matt S Zinter et al. Front Oncol. .

Abstract

Pediatric allogeneic hematopoietic cell transplant (HCT) survival is limited by the development of post-transplant infections. In this overview, we discuss a clinical approach to the prompt recognition and treatment of fever and hypotension in pediatric HCT patients. Special attention is paid to individualized hemodynamic resuscitation, thorough diagnostic testing, novel anti-pathogen therapies, and the multimodal support required for recovery. We present three case vignettes that illustrate the complexities of post-HCT sepsis and highlight best practices that contribute to optimal transplant survival in children.

Keywords: bone marrow transplant; fever; hypotension; infection; sepsis.

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Figures

FIGURE 1
FIGURE 1
Immune reconstitution following allogeneic HCT. (Left panel) Immune reconstitution gradually recovers following allogeneic HCT with donor-derived innate immune cell numbers and function preceding adaptive immunity. (Right panel) Kinetic and functional immune recovery in the allogeneic HCT recipient are affected by donor (age, immune function), graft (HSC source, cell content), and recipient (age, presence of co-morbidities and thymic involution or damage, underlying disease and associated previous therapy, type of conditioning regimen, organ dysfunction, changes in microbiome, occurrence of GvHD and associated use of immunosuppression, infection and use of supportive care pharmaceutical agents) factors. In addition, disparities in donor (D) and recipient (R) CMV serostatus, gender and HLA matching also affect donor-derived immune recovery. Defects and delays in immune reconstitution strongly associate with decreased overall survival and increased transplant-related morbidity and mortality. αβT, alpha beta T cell; B, B-cell; CMV, cytomegalovirus; DC, dendritic cell; γδT, gamma delta T cell; GvHD, graft-versus-host disease; HLA, human leukocyte antigen; HSC, hematopoietic stem cell; MΦ, macrophage; Mono, monocyte; NK, natural killer; PMN, polymorphonuclear cell; Pro, progenitor cell; Treg, T regulatory cell.
FIGURE 2
FIGURE 2
Risk factors for blood stream infection in allogeneic hematopoietic cell transplant recipients. (Left column) Transplant, donor, allograft and recipient factors are associated with risk for bloodstream infection (BSI). Higher risk patients should be monitored closely for the development of BSI in order to initiate prompt treatment aimed at preventing progression to severe sepsis or septic shock. GvHD, graft-versus-host disease; MBI, mucosal barrier injury; IST, immunosuppressive therapy; PICC, peripherally inserted central catheter.
FIGURE 3
FIGURE 3
Invasive viral infection in allogeneic hematopoietic cell transplant recipients. Risk factors (left), target organs and clinical manifestations (center) and post-transplant outcomes affected by DNA viruses (right) are depicted. Patients at risk for dsDNA viremia should be monitored closely for the development of DNA reactivation or de novo infection and should be treated promptly in order to prevent progression to severe multi-organ injury (MOI). A, ADV, adenovirus; αCD52, anti-CD52 monoclonal antibody (alemtuzumab); ATG, antithymocyte globulin; B, BK virus; C, CMV, cytomegalovirus; D/R, donor/recipient; E, EBV, Epstein-Barr virus; GvHD, graft-versus-host disease; H6, HHV-6, human herpesvirus 6; H, HSV, herpes simplex virus; HLA, human leukocyte antigen; UCB, umbilical cord blood; V, VZV, varicella zoster virus; ↑, increases; ↓, decreases.
FIGURE 4
FIGURE 4
Invasive fungal infection in allogeneic hematopoietic cell transplant recipients. Risk factors (left), target organs and clinical manifestations (center) and post-transplant outcomes affected by representative fungi (right) are illustrated. Keys to best outcomes following IFI include adequate source control, proper antifungal therapy and most importantly restoration in antifungal immunity. ASP, Aspergillus spp.; ATG, antithymocyte globulin; BM, bone marrow; CAN, Candida spp.; GvHD; graft-versus-host disease; HLA, human leukocyte antigen; MAb, monoclonal antibody; PB, peripheral blood; UCB, umbilical cord blood; ↑, increases; ↓, decreases.
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References

    1. Azoulay E, Pene F, Darmon M, Lengline E, Benoit D, Soares M, et al. Managing critically Ill hematology patients: time to think differently. Blood Rev. (2015) 29:359–67. 10.1016/j.blre.2015.04.002 - DOI - PubMed
    1. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. (2013) 369:840–51. 10.1056/NEJMra1208623 - DOI - PubMed
    1. Goldstein B, Giroir B, Randolph A. International consensus conference on Pediatric S. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. (2005) 6:2–8. 10.1097/01.PCC.0000149131.72248.E6 - DOI - PubMed
    1. Lindell RB, Gertz SJ, Rowan CM, McArthur J, Beske F, Plunkett A, et al. High levels of morbidity and mortality among pediatric hematopoietic cell transplant recipients with severe sepsis: insights from the sepsis PRevalence, OUtcomes, and therapies International point prevalence study. Pediatr Crit Care Med. (2017) 18:1114–25. 10.1097/PCC.0000000000001338 - DOI - PMC - PubMed
    1. Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. (2013) 50:23–36. 10.3109/10408363.2013.764490 - DOI - PMC - PubMed

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