Two novel assays demonstrate persistent daratumumab exposure in a pediatric patient with delayed engraftment following allogeneic hematopoietic stem cell transplantation.

BACKGROUND AIMS: Daratumumab, a human IgG monoclonal antibody targeting CD38, is a promising treatment for pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL). We describe a case of delayed engraftment following a mismatched, unrelated donor hematopoietic stem cell transplant (HSCT) in a 14-year-old female with relapsed T-ALL, treated with daratumumab and chemotherapy. By Day 28 post-HSCT, the patient had no neutrophil engraftment but full donor myeloid chimerism. METHODS: We developed two novel, semi-quantitative, antibody-based assays to measure the patient's bound and plasma daratumumab levels to determine if prolonged drug exposure may have contributed to her slow engraftment. RESULTS: Daratumumab levels were significantly elevated more than 30 days after the patient's final infusion, and levels inversely correlated with her white blood cell counts. To clear daratumumab, the patient underwent several rounds of plasmapheresis and subsequently engrafted. CONCLUSIONS: This is the first report of both delayed daratumumab clearance and delayed stem cell engraftment following daratumumab treatment in a pediatric patient. Further investigation is needed to elucidate the optimal dosing of daratumumab for treatment of acute leukemias in pediatric populations as well as daratumumab's potential effects on hematopoietic stem cells and stem cell engraftment following allogenic HSCT.

Irreducible Posterolateral Fracture Dislocation of the Knee in an Elderly Patient Treated with Rotating Hinge Total Knee Replacement.

Knee dislocation is one of the few real orthopaedic emergencies. It is a serious but relative uncommon injury, representing less than 0.02% of all orthopaedic injuries. Especially posterolateral knee dislocation is much rarer condition that is often missed or misdiagnosed. The main feature of this very rare condition is to be irreducible by closed reduction due to the interposition of soft tissues inside the enlarged medial joint space, such as the medial capsule and retinaculum, vastusmedialis, and medial meniscus. The pathognomonic sign of a posterolateral knee dislocation is the anteromedial distal thigh transverse "pucker" or "dimple sign." We report the case of an 87-year-old man who sustained an irreducible posterolateral fracture dislocation of the knee after being hit by car which has been treated with rotating hinge knee replacement with 1-year of follow-up.