Patient Characteristics Associated with Successful Mobilization of Peripheral Blood Stem and Progenitor Cells Following Cytotoxic Chemotherapy and Peg-G-CSF Stimulation.
Authors: Bruns Ingmar , Fischer Johannes C. , Czibere Akos G. , Kilic Cangül , Fenk Roland , Zohren Fabian , Kronenwett Ralf , Haas Rainer , Kronenwett Ralf 
Published: October 2019

Abstract
Mobilized peripheral blood stem and progenitor cells are nowadays widely used for transplantation of hematopoietic stem and progenitor cells (PBSCT). These cells can be mobilized into the peripheral blood with cytotoxic chemotherapy, cytokines or both. Currently, G-CSF is most frequently used due to its high efficacy and lack of serious toxicity. However, a serious patient-to-patient variation in the yield of peripheral blood stem and progenitor cells is a feature common of all mobilizations schemes. Therefore, factors determining the collection efficacy have been identified for G-CSF mobilization. Recently a polyethylenglycole-conjugated G-CSF (Peg-G-CSF) has been introduced which has a 12-fold longer half-life than the original compound and therefore leads to long-lasting G-CSF serum-levels after a single injection. Studies on Peg-G-CSF included only small cohorts and no attempts have been made to identify factors influencing the mobilization of blood stem and progenitor cells. Therefore, we retrospectively analyzed 101 unselected patients (66 with multiple myeloma, 26 with non-Hodgkin-lymphoma, 7 with Hodgkin’s disease, 1 with Ewing sarcoma, 1 with malignant germ cell tumor). 27% of patients had active disease, while all others where at least in partial remission after conventional chemotherapy. Patients were treated with a broad range of chemotherapy regimens. The number of cytotoxic chemotherapy cycles administered prior to the mobilization therapy ranged from 1 to 11 (median 4). Mobilization chemotherapy was followed by 6 mg or 12 mg Peg-G-CSF (median 6 mg). Median peripheral blood CD34+ cell maximum in all patients was 65.3/μl (range 0.2–1084 per μl). 12 mg Peg-G-CSF led to a significantly earlier CD34+ cell maximum in the peripheral blood compared to 6 mg Peg-G-CSF (median 13 days vs 15 days, respectively; p=0.01). Overall, a median yield of 8.5 x 10^6 CD34+ cells/kg bodyweight (range 0.2–72.4 x 10^6) was reached with a single apheresis (median, range 1–4). To search for predictors of hematopoietic stem and progenitor cell mobilization, multiple regression analysis was used and revealed CD34+ cell count/μl peripheral blood at the day of apheresis and the processed blood volume during apheresis as predictors for the CD34+ cell yield per kilogram bodyweight. Age, sex, disease type and status were not significantly related to the CD34+ cell count/μl peripheral blood nor the CD34+ cell yield. Interestingly, the number of previous chemotherapy cycles was correlated with the CD34+ cell maximum (p=0.027) with fewer chemotherapy cycles leading to a higher peripheral blood CD34+ cell count and vice versa. In contrast, radiation therapy prior to CD34+ cell mobilization led to a significantly later occurrence of the CD34+ cell maximum in the peripheral blood. Our results confirm the feasibility and efficacy of PBPC mobilization with single dose Peg-G-CSF after cytotoxic chemotherapy shown in previous clinical trials analyzing the largest patient cohort to date and predictors for successful stem cell mobilization with Peg-G-CSF could be identified.