Role of neutropenic diet in prevention of infection and graft-versus-host disease in haematopoietic stem cell transplant recipients: systematic review and meta-analysis protocol

Introduction: Haematopoietic stem cell transplantation (HSCT) is associated with substantial early infectious risk, neutropenia, immunosuppression, and graft-versus-host disease (GVHD). Many centres continue to use neutropenic, low-microbial, low-bacterial, or protective diets to reduce dietary exposure to potential pathogens, despite variation in diet definitions and concerns regarding nutritional intake, patient experience, cost, and microbiota recovery. This protocol describes a systematic review and meta-analysis evaluating the benefits and harms of neutropenic diets compared with less restrictive, standard, or food-safety-based dietary approaches in HSCT recipients.

Methods: We will include randomised and non-randomised comparative studies involving children or adults undergoing HSCT from any graft source and conditioning intensity. Eligible interventions will include neutropenic, low-microbial, low-bacterial, or protective diets; comparators will include unrestricted, less restrictive, standard hospital, or food-safety-based diets. MEDLINE, Embase, CENTRAL, Web of Science, CINAHL, Scopus, ClinicalTrials.gov, and the WHO ICTRP will be searched from inception without language or date restrictions, supplemented by reference screening, expert contact, grey literature, and conference proceedings. Two reviewers will independently screen studies, extract data, and assess risk of bias using RoB 2 for randomised trials and RoBANS for non-randomised studies.

Results: The primary outcomes will be infection rates, acute GVHD, nutritional status, time to neutrophil recovery, and patient satisfaction or quality of life. Secondary outcomes will include overall survival, relapse, chronic GVHD, length of hospitalisation, antibiotic use to day 100, micronutrient deficiency, and cost outcomes. Where appropriate, pooled estimates will be generated using random-effects models, with subgroup and sensitivity analyses used to explore heterogeneity. Certainty of evidence will be assessed using GRADE.

Discussion: This review will clarify whether neutropenic diets reduce infectious complications or GVHD after HSCT, and whether any potential benefit is offset by nutritional, patient-centred, microbiome-related, or economic harms. Findings will inform clinical practice, patient counselling, and future policy on dietary restrictions after HSCT.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251162724, identifier PROSPERO (CRD420251162724).