Beneficial Effects of G-CSF Dosage Adaption in Allogeneic Stem Cell Donors That Are at Risk for Poor Mobilization. Retrospective Dual Center Analysis of 5691 Allogeneic Stem Cell Mobilizations

Peripheral blood stem cells (PBSC) are the major source for allogeneic stem cell transplantations. It has been shown that treatment with 7,5 µg/kg G-CSF for 5 days is sufficient to mobilize and collect required CD34+ cells for transplantation. However, uncertainty remains in 0.5 – 5.0% of all donors regarding insufficient mobilization. In this retrospective analysis we evaluated 5691 allogeneic stem cell mobilization regimens (72% male vs. 28% female donors) from two major collection centers focusing on donor risk factors for poor mobilization. According to our historical reciprocal weight and BMI-adapted mobilization protocol low weight/low BMI donors received > 8.3µg/kg/d for 4 days, whereas overweight donors received <7.5 µg/kg. At day 5 all donors received 526µg G-CSF 2 hours before apheresis. In total, a mean G-CSF-dosis of 8.9 ± 1.0µg/kg/d for 5 days has been utilized (min 4.5µg/kg/d – max. 15.9µg/kg/d). Mean CD34+ cell concentration of 95 ± 49/µl could be achieved in the peripheral blood at day 5 before starting apheresis. This enabled us to collect a mean of 9.7 ± 8.0 CD34+ cells/kg body weight recipient corresponding to 658 ± 252 million total CD34+ cells in the product. In 96.3% of all cases one single apheresis was sufficient to collect the requested amount of CD34+ cells. Using logistic regression analysis we defined female sex, low BMI and low platelet (PLT) count at baseline as strongest risk factors for poor mobilization. Low white blood cell (WBC) concentration, low hematocrit and G-CSF-dosis < 9µg/kg/d were also significantly associated with poor mobilization. Using the strongest numeric predictors (BMI, PLT) we employed STEPP-analysis to establish a statistically significant cross table risk score, that allows prediction of CD34+ cells in the peripheral blood at day 5 according to baseline PLT and BMI. From lowest cumulative risk score 2 (PLT>290; BMI>34.5) to highest risk score 6 (PLT<170; BMI<20.7) differences between all risk scores were highly significant. Interestingly, subgroup analysis demonstrated that female – but not male donors with poor risk score that received > 9µg/kg/d G-CSF could improve significantly mobilization outcome without further side effects. Thus, overall results demonstrated that weight adapted G-CSF dosage for allogeneic donor treatment may improve mobilization outcome, i.e. in poor risk prospect female donors with low BMI and low PLT at baseline. Further genetic analysis may identify factors responsible for mobilization outcome.