Successful treatment of two cases with Philadelphia-chromosome positive acute lymphoblastic leukemia who relapsed after allogeneic stem cell transplantation and the treatments with novel immunotherapies and ponatinib

Two case studies illustrate the potential for CAR T-cell therapy or a second allogeneic hematopoietic stem cell transplantation (HCT) with a sequential conditioning regimen in the treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) that is resistant to multiple immunotherapies. In the first case, a 15-year-old boy with Ph+ALL experienced hematologic relapse after a second HCT following treatment with ponatinib and blinatumomab. After receiving CAR-T therapy, the patient experienced negative measurable residual disease, which continued for 38 months without maintenance therapy. In the second case, a 21-year-old man with Ph+ALL experienced hematologic relapse after the first HCT and did not achieve hematologic remission despite treatment with multiple immunotherapies. He received a second HCT using a sequential conditioning regimen with clofarabine, and as a result, achieved and maintained negative measurable residual disease for 42 months without maintenance therapy.