Case Report: Safety and efficacy of blinatumomab in combination with donor lymphocyte infusion for the prophylaxis of relapse following allogeneic hematopoietic stem cell transplantation in a pediatric patient with acute lymphoblastic leukemia.

Background: Acute lymphoblastic leukemia (ALL) is the most common malignant hematological disease in children. Patients with high-risk ALL have a poor prognosis, and allogeneic hematopoietic stem cell transplantation (HSCT) is one of the important treatment modalities. However, post-transplant relapse of the primary disease remains one of the leading causes of treatment failure, seriously affecting the long-term survival of patients. Donor lymphocyte infusion (DLI) has been shown to have some efficacy in preventing relapse in B-cell ALL after HSCT, while the use of blinatumomab for preventing post-transplant relapse in ALL remains under investigation. Moreover, the safety and efficacy of the combination regimen for this indication still need to be verified in larger patient cohorts. We herein report a single case of a child with high-risk ALL who received blinatumomab combined with prophylactic DLI to prevent relapse after HSCT, along with a brief review of the relevant literature. Case presentation: A 5-year-old boy was diagnosed as ALL, early pro-B, KMT2A::USP2 fusion gene positive. After induction treatment with the SCCLG-ALL-2016 protocol, the minimal residual disease (MRD) by flow cytometry(FCM) and the quantitative PCR of KMT2A::USP2 fusion gene and NGS IGH remained continuous positive. The child received one cycle of blinatumomab, and the MRD by FCM and RQ-PCR turned negative after the blinatumomab regimen. Another two weeks of blinatumomab was given as bridge and then haploidentical HSCT was performed. Because his MRD by NGS IGH was 0.0311% before HSCT, the child received 3 cycles of blinatumomab and two prophylactic DLIs to prevent post-transplant relapse. During the treatment with blinatumomab and DLI, the child developed grade 1 cytokine release syndrome (CRS), without other severe adverse reactions such as neurotoxicity, hypoxemia, and hypotension. Conclusion: In this pediatric patient with high-risk KMT2A::USP2-positive ALL, sequential blinatumomab plus prophylactic DLI was well-tolerated and maintained sustained remission after HSCT. This case preliminary supports the combined regimen for post-transplant relapse prevention in high-risk patients. Given case report limitations, larger prospective trials are needed to verify its safety, efficacy and optimal dosing for widespread clinical use.