Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia

Abstract

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2Á2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3Á75; 95% CI 1Á51-9Á37; P = 0Á004) and with increasing age (OR 3Á58; 95% CI 1Á24-9Á77; P = 0Á01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9Á43; 95% CI 1Á47-60Á66; P = 0Á02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6Á42; 95% CI, 1Á01-40Á94; P = 0Á05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 AE 8% and five-year overall survival was 70 AE 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable. ALL, acute lymphoblastic leukaemia; AML, acute myeloid leukaemia; SCT, stem cell transplantation. *Variables are presented as n (%), unless otherwise stated. † The dash indicates that the variable was entered into the initial multivariate logistic regression model based on its P value in the univariate analysis (≤0Á10), but it was removed from the final model through the backward elimination procedure. ‡ Lymphocytopenia and monocytopenia were not included in the multivariate analysis as only a subcategory of patients had evaluable data. Surgical interventions were not included in order to avoid possible selection bias. SCT was not included due to its high correlation with relapsed and refractory disease (phi coefficient = 0Á78 and 0Á65, respectively).

Mucormycosis in Children With Hematologic Malignancies: A Case Series and Review of the Literature

“…17 In the literature review, all series but one reported the highest incidence of mucormycosis during induction therapy, which is in line with our case series. 5,8,9,14,17–20…”

“…Significant corticosteroid use was defined as an administration of 2 mg/kg/d prednisone or equivalent for at least 10 days in the month before the diagnosis of mucormycosis. 8…”

“…[4][5][6][7] However, very little data regarding the incidence of mucormycosis in pediatric hemato-oncology patients exist, available studies report an incidence of 0.3% and 2.2%. 8,9 Mucormycosis is caused by fungi of the order Mucorales. Most frequently reported pathogens of this order are Rhizopus, Mucor and Lichtheimia species.…”

COVID-19 associated mucormycosis in head and neck region of children during current pandemic: Our experiences

“…Hematological malignancy is an important risk factor for mucormycosis [13]. In one study, the incidence of mucormycosis among children with acute lymphoblastic leukemia (ALL) was 2.2% [14]. Acute lymphoblastic leukemia and increasing age were two important risk [15].…”

Central Nervous System Mold Infections in Children with Hematological Malignancies: Advances in Diagnosis and Treatment

“…A systematic review including patients up to 2005 found a mortality of 82.8% of CNS aspergillosis reported before 1990, while that of patients reported after 1990 was 39.5% [83]. In a recent analysis on immunocompromised children suffering from mucormycosis, five out of eight patients (62.5%) with rhino-cerebral involvement died, but it has to be noted that the outcome of invasive aspergillosis is generally better than that of mucormycosis [10,11]. Another analysis of 29 immunocompromised children diagnosed with CNS IMD between 2007 and 2016 reported that the probability of 2-year survival was 48.9% [22].…”