Background: It is expected that blinatumomab will be increasingly incorporated into the care of children with B-lineage acute lymphoblastic leukemia (B-ALL) based on improved survival for subsets of patients, and a favorable safety profile. Most of the 28-day continuous infusion can be administered in outpatient or home settings. Limited studies have described low rates of complications at home when appropriate safety plans are in place. However, home administration shifts the burden of monitoring and care to caregivers. Procedure: Caregivers of children with B-ALL within one month of completing a first cycle of blinatumomab at home were recruited from three tertiary care centers and participated in virtual, audio-recorded, semi-structured interviews, with translation services available as required. Interviews were transcribed, coded independently in duplicate, and analyzed using thematic analysis. Identified caregiving context-specific barriers and facilitators were coded deductively. Results: Participating caregivers (n=21) described a timebound confidence response where initial infusion anxiety was gradually replaced with caregiving self-assurance. Growing confidence co-occurred with improved caregiver wellness and child quality of life characterized by resuming more usual family activities amid therapy. Barriers and facilitators to successful home-based blinatumomab included caregiver, access to hospital-based support, and particular aspects of a family’s social and material environment and these underpinned recommendations for future caregivers. CONCLUSIONS: Caregivers can confidently manage home-based continuous infusion blinatumomab with anticipatory guidance and support and with attention paid to context-related modifiers to care. Caregiver insights should be reflected in the principles that become the basis of future pediatric B-cell ALL clinical trials and care.