Late oral adverse effects of chemotherapy for hematological malignancies in children: A systematic review and meta-analysis of case-control studies

Background: The purpose of the present systematic review and meta-analyses was to appraise the case-control studies that have evaluated late adverse effects of chemotherapy for treating hematological malignancies in pediatric patients.

Methods: Five electronic databases along with grey literature were searched using broad keywords and MeSH terms for the articles that could meet the eligibility criteria. The Newcastle-Ottawa Scale was employed for quality assessment. DerSimonian and Laird random effects model using the (Restricted Maximum Likelihood) REML approach was used for meta-analyses to calculate the pooled Odds Ratios (ORs) for binary outcomes and Standardized Mean Difference (SMD) for continuous outcomes. The GRADE approach was used to synthesize the certainty of evidence utilizing GRADEpro® GDT software.

Results: 8,052 records were obtained from the searches. After duplicate removal and initial screening of titles and abstracts, 109 articles were subjected to full-text reading but only 5 could be included. The pooled ORs of having root malformation, microdontia, tooth agenesis, taurodontism, and enamel defects in patients who have undergone treatment were 7.68, 5.39, 3.74, 2.00, and 1.84 compared to controls, respectively. The SMD for dental caries was also significant among the groups (p= 0.03) and indicated an SMD of 0.27 (95% CI: 0.03, 0.51) indicating higher pooled mean DMFT in the cases than controls.

Conclusions: Root malformations are associated with treatment for childhood hematological cancers with a moderate certainty of assessment. Tooth agenesis and microdontia are associated with low certainty of evidence, while taurodontism, enamel defects, and caries were associated with very low certainty of evidence. Future studies on larger sample sizes are needed to validate the findings as the number of studies included in our review was small.