Infectious Complications in Paediatric Haematopoetic Cell Transplantation for Acute Lymphoblastic Leukemia: Current Status

Abstract

Haematopoietic stem cell transplantation (HSCT) in paediatric patients with acute lymphoblastic leukaemia (ALL) is associated with a variety of infectious complications which result in significant morbidity and mortality. These patients are profoundly immunocompromised, and immune reconstitution after HSCT generally occurs in astrictly defined order. During the early phase after HSCT until engraftment, patients are at risk of infections due to presence of neutropenia and mucosal damage, with Gramme-positive and Gramme-negative bacteria and fungi being the predominant pathogens. After neutrophil recovery, the profound impairment of cell-mediated immunity and use of glucocorticosteroids for control of graft-vs.-host disease (GvHD) increases the risk of invasive mould infection and infection or reactivation of various viruses, such as cytomegalovirus, varicella zoster virus, Epstein-Barr virus and human adenovirus. In the late phase, characterised by impaired cellular and humoral immunity, particularly in conjunction with chronic GvHD, invasive infections with encapsulated bacterial infections are observed in addition to fungal and viral infections. HSCT also causes a loss of pretransplant naturally acquired and vaccine-acquired immunity; therefore, complete reimmunization is necessary to maintain long-term health in these patients. During the last two decades, major advances have been made in our understanding of and in the control of infectious complications associated with HSCT. In this article, we review current recommendations for the diagnosis, prophylaxis and treatment of infectious complications following HSCT for ALL in childhood.

Conference Report 33rd European Congress on Clinical Microbiology and Infectious Diseases (ECCMID): New developments in pediatric oncology infectious disease supportive care

“…There were no deaths in the global cohort and no intensive care unit (ICU) admission in the "ECIL" group, compared to two ICU admissions in the "non-ECIL" group. EAT courses for FUO episodes were significantly shorter in the ECIL group (4 [3][4][5] vs. 10 [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] days; p = .002), with a mean reduction of 9 ± 3 days. Fourteen (27%) episodes of recurrent fever were observed with six documented bloodstream infections.…”

“…tant for the control of a certain type of organism and are nowadays mostly understood. 3,4 Effective risk-based approaches to the prevention and early treatment of the most relevant infectious complications have been developed, including antiviral and antifungal prophylaxis, empirical antifungal and antibacterial, and pre-emptive antifungal and antiviral therapies. [5][6][7][8][9] However, despite these advances and an overall low infectious mortality in the affected patients, infectious complications in the immunocompromised host remains a dynamic and ever-evolving field that requires continuous daily attention in the form of surveillance, institution and auditing of standards of care, a high level of suspicion to new infections and new types of known infections, and interdisciplinary collaboration, discussion, and publicity.…”

“…Hospital admission, disease‐ and treatment‐induced disruptions of the skin and mucosal barriers, and the suppression of innate and acquired host defenses are the major drivers of infectious morbidity in pediatric cancer and allogeneic hematopoietic cell transplant (HCT) patients, and they result in an inherent risk for rapidly evolving and potentially life‐threatening systemic bacterial, fungal, viral, and parasitic infections. The infectious risks depend on the underlying disease, the type and phase of treatment, and the host defenses important for the control of a certain type of organism and are nowadays mostly understood 3,4 . Effective risk‐based approaches to the prevention and early treatment of the most relevant infectious complications have been developed, including antiviral and antifungal prophylaxis, empirical antifungal and antibacterial, and pre‐emptive antifungal and antiviral therapies 5–9 .…”

Epidemiology of bloodstream infections and the impact of antimicrobial resistance in pediatric hematopoietic cell transplant

“…The risk of infection post HSCT can be categorized into three distinct time periods: pre-engraftment; post-engraftment, and late phase. 1,2 The highest incidence of infectious morbidity and mortality is observed in patients with granulocytopenia, especially in the pre-engraftment period. Indeed, different studies showed that 39%-60% of all BSIs occurred in the pre-engraftment period.…”

Stopping antibacterial prophylaxis in pediatric allogeneic hematopoietic cell transplantation: An internal audit

“…Over the past five decades, allogeneic hematopoietic cell transplantation (HCT) has become a standard of care for children and adolescents with high‐risk leukemia, bone marrow failure syndromes, and several nonmalignant hematological disorders including severe immunodeficiency and certain inborn errors of metabolism 1–3 . Whereas the majority of patients will be cured, allogeneic HCT is associated with relevant and potentially life‐threatening complications in a substantial proportion of patients: Apart from leukemic relapse, graft‐versus‐host disease (GVHD), and treatment‐induced organ toxicities, treatment‐induced suppression of innate and acquired host defenses is a major driver of posttransplant morbidity and mortality, as it results in a high risk for potentially life‐threatening systemic bacterial, fungal, and viral infections 4,5 . The risk depends on the post‐HCT period and the host defenses important for the control of a certain type of organism: For invasive bacterial infections, the risk is highest during the granulocytopenic phase until engraftment, but continues at an elevated level postengraftment due to the presence of central venous catheters and increased immunosuppression and damaged tissue barriers in case of GVHD 6,7 …”