Alemtuzumab Controls Acute GVHD and Mixed Chimerism Risks in Pediatric Patients with HLH Undergoing Stem Cell Transplantation: A Correlative Biology Study from the CTN 1204 Richi Trial

Abstract

A reduced intensity conditioning regimen consisting of alemtuzumab, fludarabine, and melphalan has been shown to be associated with superior survival in patients with hemophagocytic lymphohistiocytosis, but is complicated by a high risk of mixed chimerism and secondary graft failure. We hypothesized that peri-transplant alemtuzumab levels impact the risks of both acute GVHD and mixed chimerism in patients with HLH undergoing RIC HCT. We tested this hypothesis in a companion correlative biology study to the Blood and Marrow Transplant Clinical Trials Network (CTN) prospective 1204 trial, Reduced-Intensity Conditioning for Children and Adults with Hemophagocytic Syndromes or Selected Primary Immune Deficiencies. The HCT RIC regimen included alemtuzumab (mg/kg subcutaneous, maximum cumulative dose of 90mg, divided over days −14 through −10), fludarabine (150mg/m2 or 5mg/kg in patients Our cohort was 74% male with a median age of 2.1 years (range 0.4-18.9). Nine patients (39%) developed acute GVHD not associated with donor lymphocyte infusion (DLI). Acute GVHD was associated with lower Day 0 alemtuzumab levels. Sixty-seven percent of patients with Day 0 levels 0.67μg/ml (p=0.0078) (Figure 1). Seventeen patients (74%) developed mixed chimerism, defined as whole blood donor chimerism Alemtuzumab level at day 0 significantly impacts the risks of acute GVHD and mixed chimerism. Studies to test precision dosing strategies to target peri-transplant levels of alemtuzumab to appropriate therapeutic ranges are underway, and future implementation may lead to improved outcomes.