Combined CAR-T/HSCT approach in a patient with refractory acute lymphoblastic leukemia and cystic fibrosis

Introduction: The association of acute lymphoblastic leukaemia (ALL) and cystic fibrosis (CF) is rare. We present the case of a paediatric patient affected by CF and refractory B-cell precursor (BCP) ALL, who was treated with combined chimeric antigen receptor T-cells (CAR-T) and allogeneic haematopoietic stem cell transplantation (HSCT). Case description: Autologous-CD19 targeting CAR-T allowed to achieve molecular remission and spare chemo-related toxicity. As B-cell aplasia was not achieved, the patient underwent HSCT after total body irradiation (TBI)-based conditioning. The course after HSCT was complicated by veno-occlusive disease, status epileptic and pulmonary invasive fungal infection which showed progressive radiological worsening despite aggressive treatment. Five months after HSCT a left upper lobe lobectomy was successfully performed. Thirteen months after HSCT the patient is in complete disease remission with normal lung function. Conclusions: CAR-T cell therapy bridge-to-HSCT may be an effective approach in paediatric refractory ALL in the context of multiple comorbidities as observed in CF.