Case Report: donor cell-derived leukemia after allogeneic stem cell transplantation for metastatic renal cell carcinoma.

Donor cell-derived leukemia (DCL) is a rare complication of allogeneic hematopoietic cell transplantation (allo-HCT), previously described in patients receiving allo-HCT for hematologic malignancies. Allo-HCT has also been investigated as an immunotherapy platform for solid tumors including clear cell renal cell carcinoma (RCC). Herein, we describe a unique patient case treated by allo-HCT for RCC who subsequently developed DCL. A 40-year-old man was diagnosed with metastatic clear cell RCC treated surgically by left nephrectomy plus metastasectomy of a rib lesion. He was referred to the Fred Hutchinson Cancer Center and treated by allo-HCT as part of a clinical trial (NCT00005851). His initial allograft following fludarabine/2 Gy total body irradiation (TBI) conditioning was complicated by graft failure. After collecting a G-CSF-mobilized autologous hematopoietic stem cell product as a failsafe for repeated graft failure, he was re-transplanted from the same donor following cyclophosphamide/antithymocyte globulin (ATG) conditioning, resulting in successful engraftment. Fourteen months later, he developed donor origin acute myelomonocytic leukemia with central nervous system (CNS) involvement. He was treated by 7 + 3 induction with intrathecal methotrexate and was able to achieve complete remission. He subsequently underwent autologous hematopoietic cell transplantation (auto-HCT) without further leukemia relapse. Unfortunately, 4 years after his auto-HCT, he developed recurrent RCC, initially managed by surgical resections. Upon further progression, he was then treated with sequential lines of systemic therapy that included pazopanib, nivolumab, cabozantinib, and lenvatinib/everolimus. He died from complications of his RCC 17 years after his second successful allograft. The absence of pre-transplant systemic therapies for the patient's metastatic RCC and ongoing good health of the donor implicates a leukemogenic potential of his transplant-associated therapies including TBI, cyclophosphamide, and ATG. His uncommonly long survival from metastatic RCC suggests clinical benefit was derived from the 14-month duration of allo-HCT associated with T-cell allo-immunity previously shown capable of targeting RCC-associated minor histocompatibility antigens.