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


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.

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The authors would like to thank all the staff of the Clinical Laboratory of Keio University Hospital for their skillful evaluations of the morphology and flow cytometry This work was supported in part by research funding from Novartis Pharma K. K. and Pfizer Inc.

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Correspondence to Takehiko Mori.

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Conflict of interest

Takehiko Mori received research funding from MSD K. K., Novartis Pharma, LSI Medience, Medical and Biological Laboratories, Otsuka Pharmaceutical, Kyowa Kirin Co., Ltd., Shionogi and Co., Chugai Pharmaceutical, Takeda Pharmaceutical and Asahi Kasei Corporation, and personal fees from Pfizer Inc., MSD K. K., Janssen Pharma, Sumitomo Dainippon Pharma, Novartis Pharma K. K., Kyowa Kirin Co., Ltd., Chugai Pharmaceutical, Shionogi and Co., Japan Blood Products Organization, Takeda Pharmaceutical, Ono Pharmaceutical, Eisai Pharmaceuticals, and Astellas Pharma; Taku Kikuchi receives a personal fee from Bristol-Myers Squibb, Takeda Pharmaceutical, Otsuka Pharmaceutical, Eisai Pharmaceuticals, Sanofi K. K. and Janssen Pharma; Masuho Saburi receives a personal fee from Nippon Shinyaku Co., Ltd.; Masatoshi Sakurai receives research funding from Nippon Shinyaku Co., Ltd.; Shinichiro Okamoto receives research funding from Novartis Pharma K. K., Pfizer Inc., Sanofi K. K., Shionogi and Co., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma and Chugai Pharmaceutical, and personal fees from Nippon Shinyaku Co., Ltd. and Sanofi K. K.

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Mori, T., Kikuchi, T., Yamazaki, R. et al. Phase 1 study of plerixafor in combination with total body irradiation-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation. Int J Hematol (2021).

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  • Plerixafor
  • Myeloablative conditioning
  • Allogeneic hematopoietic stem cell transplantation
  • Total body irradiation
  • Chemosensitization
  • Mobilization