Effect of Body Mass Index On the Mobilizing Efficacy of Plerixafor in Patients Undergoing Autologous Stem Cell Collection: A Retrospective Study

Peripheral blood has largely replaced bone marrow as the source of stem cells for autologous transplantation. The number of cells infused is a key determinant of hematopoietic recovery after transplantation. Peripheral blood stem cell (PBSC) yield can be affected by several factors such as donor characteristics, disease status and prior treatment regimens. We retrospectively analyzed the effect of body mass index (BMI) on PBSC mobilization in 164 patients with plasma cell dyscrasias. Patients were segregated based on BMI <25 (Group I), 25-30 (Group II) and >30 (Group III).  Since G-CSF is dosed according to the actual body weight, patients with higher BMI received higher total G-CSF dose (as well as higher dose per kg ideal body weight) but the median stem cell yield per kg IBW was similar in the 3 groups. (I= 2.2 x 10^3 cells/ Kg, II= 2.1 x 10^3 cells/Kg and III= 2.3 x 10^3 cells/Kg; p=0.76). We also evaluated the effect of BMI on the mobilizing efficacy of plerixafor. In our institution, patients receive G-CSF at a dose of 10 μg/Kg daily subcutaneous injections for three consecutive days. Patients with peripheral CD34+ cell count less than 10 x 10⁶ /L are considered “poor mobilizers” and plerixafor at a dose of 0.24 mg/Kg SQ daily is initiated starting on the fourth day for a maximum of four days or until target number of cells are collected. The fold increase in the median peripheral blood CD34+ count after one dose of plerixafor was 8.1 (7.1-> 57.2 /uL), 6.8 (7.2-> 49.5 /uL) and 3.6 (11-> 40.3 /uL) in BMI groups I, II and III, respectively (p=0.0675). Similarly, the administration of plerixafor in addition to G-CSF did not give as much benefit in stem cell yield in higher BMI groups as seen in BMI < 25 group (p=0.0063 in BMI<25 group and p=0.30 in BMI >30). The reasons for these effects are unclear. Homing of the HPCs in the adipose tissue (AT) may be a factor in higher BMI individuals as the adipose tissue has similar biochemical and molecular microenvironment as the bone marrow.  The pathophysiologic changes associated with obesity may alter the pharmacokinetics and pharmacodynamics of subcutaneously administered drugs leading to their impaired efficacy. We believe these initial observations may have important implications for clinical practice. Prospective studies are needed to validate these findings and explore whether these effects can be mitigated by intravenous route of plerixafor administration.