Monitoring of cytomegalovirus infection in non-transplant pediatric acute lymphoblastic leukemia patients during chemotherapy

Abstract

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality in the posttransplant setting; however, it is increasingly recognized in pediatric leukemia during chemotherapy. This study assessed the prevalence and associated factors of CMV infection in pediatric non-transplant leukemia patients.This was a cross-sectional study of 50 pediatric acute lymphoblastic leukemia (ALL) patients receiving chemotherapy at Ramathibodi Hospital from December 2015 to December 2016. CMV viral load quantified by DNA polymerase chain reaction (PCR) was monitored in different phases of chemotherapy: enrolment, post-induction, post-consolidation, post-intensification, and maintenance.One hundred forty one blood tests were evaluated from 50 patients. Overall prevalence of CMV DNAemia (≥20 copies/mL) and high-level CMV DNAemia (≥1000 copies/mL) was 52% (26 of 50) and 16.0% (8 of 50), respectively. All patients with high-level CMV DNAemia were in the maintenance phase of chemotherapy. One patient had CMV retinitis, while the rest had no end-organ CMV diseases. Increased lymphocyte count was significantly associated with protection from high-level CMV DNAemia (odds ratio 0.997, P = .02). Receiver operating characteristic curve identified a cut-off value of 798 cells/mm3 of absolute lymphocyte count (ALC) as a discriminator for the presence of high-level CMV DNAemia (area under the curve 0.756, 95% CI 0.645–0.867, P = .001) with 88.9% sensitivity and 50.4% specificity.CMV infection predominantly occurred during maintenance chemotherapy. Low ALC was significantly associated with high-level CMV DNAemia. CMV infection surveillance by quantitative CMV DNA PCR during maintenance chemotherapy in patients with ALC <800 cells/mm3 may be considered.

Co-infections of human herpesviruses (CMV, HHV-6, HHV-7 and EBV) in non-transplant acute leukemia patients undergoing chemotherapy

“…Reconstitution of B lymphocytes and Natural killer cells occurs early while T cell reconstitution shows delayed recovery of both T helper and T suppressor cells [25]. Higher risk of herpes viral infection during post-remission phases of chemotherapy in acute leukemia patients was also previously reported in adult and pediatric populations especially infected with CMV and HHV-6 infections [17,19,[26][27][28].…”

“…Furthermore, the use of salvage chemotherapy (relapsed/refractory) was associated with the significant increase in CMV and HHV-6 infections in univariate analysis but not in multivariate analysis in CMV infections. This increase might be due to exposure to more selective suppressive chemotherapy such as fludarabine and the use of high-dose of steroids which depresses CD4 T-lymphocyte leading to a prolonged lymphopenia or T-cell dysfunction [6,7,[28][29][30][31]. However, paradoxical recent data suggest that CMV replication may protect against AML relapse after allo-HSCT [32].…”

Are CMV-predictive scores in inflammatory bowel disease useful in clinical practice?

“…Reviewing the literature, the current European and German guidelines did not provide cutoff levels for CMV-PCR in blood for patients with UC [1,2] or hematological neoplasms [8], and the cutoff in different studies in patients with different kinds of immunosuppression reach from 205 up to 30,000 copies/ml [9,10] with most studies using cutoffs of more than 1000 copies/ml. A recent study in patients with leukemia defined 1000 copies/ml as high CMV viremia [11]. Since not detecting a CMV infection represents a huge problem in therapy, we decided to use the cutoff of 1000 copies/ml to reach the minimum level that is seen as high CMV viremia.…”

Systemic viral infection in children receiving chemotherapy for acute leukemia

“…9 In 52% of the patients, CMV-DNAemia (defined as ≥20 copies/mL) was detected, and 16% of the children had high-level DNAemia (defined as ≥1000 copies/mL). 9 All eight patients with high-level DNAemia were in maintenance therapy and had lymphocyte counts < 800/µL. Treatment was at the discretion of the attending physician, and five out of the eight patients with highlevel DNAemia received treatment with ganciclovir, whereas three children did not receive antiviral therapy.…”

“…Abbreviations: ADV, adenovirus; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CMV, cytomegalovirus; HSCT, hematopoietic stem cell transplantation; HSV, herpes simplex virus; PCR, polymerase chain reaction; PVB 19, parvovirus B19; VZV, varicella zoster virus control is an important aspect of supportive cancer care. However, data on the occurrence of viremia of common viral pathogens are scarce and based on small and retrospective studies, 8,9 and information on symptomatic viral infections is mostly limited to case reports.…”