Phase 1 study of plerixafor in combination with total body irradiation-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation.

Takehiko Mori, Taku Kikuchi, Rie Yamazaki, Yuya Koda, Masuho Saburi, Masatoshi Sakurai, Naoyuki Shigematsu, Shinichiro Okamoto, Jun Kato

International journal of hematology 2021 Jun

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Plerixafor, a CXCR4 inhibitor, has the potential to mobilize leukemic cells, which may contribute to their chemosensitization. This phase 1 study evaluated the safety of myeloablative conditioning combined with plerixafor for allogeneic hematopoietic stem cell transplantation (HSCT). Patients with high-risk leukemia undergoing allogeneic HSCT after total body irradiation (TBI, 12 Gy)-based myeloablative conditioning were eligible; 9 patients were enrolled. The study was performed using a 3 + 3 design with an escalating total dose of plerixafor. Plerixafor was given subcutaneously 8 h before TBI and chemotherapeutic agents. Plerixafor was successfully escalated to the maximum dose (0.72 mg/kg) without dose-limiting toxicities. Underlying diseases were acute myelogenous and lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. As adverse events, plerixafor administration was associated with transient Grades 2-3 diarrhea (n = 7) and abdominal pain (n = 4). In 6 patients, leukemic cell mobilization into the peripheral blood by plerixafor was confirmed by a morphological or molecular method. All patients achieved neutrophil engraftment and 5 were alive in remission at a follow-up after 30-40 months. Plerixafor-combined myeloablative conditioning for allogeneic HSCT was well tolerated. Leukemic-cell mobilization into peripheral blood was observed in half of the patients. Further study is required to evaluate the efficacy and safety of this concept.

Citation

Takehiko Mori, Taku Kikuchi, Rie Yamazaki, Yuya Koda, Masuho Saburi, Masatoshi Sakurai, Naoyuki Shigematsu, Shinichiro Okamoto, Jun Kato. Phase 1 study of plerixafor in combination with total body irradiation-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation. International journal of hematology. 2021 Jun;113(6):877-883