In healthy adult donors undergoing blood stem cell mobilization, we previously showed that the single strongest factor related to peak pre-apheresis circulating CD34+ cell counts was the total dose of granulocyte colony-stimulating factor (G-CSF) administered to the donor. Donor weight and gender were also highly correlated with peak CD34+ cell mobilization, to the degree that they contributed to the total dose of G-CSF administered. To determine if this relationship applied to younger donors, we analyzed the factors affecting PBSC mobilization in healthy allogeneic pediatric subjects.
A retrospective analysis of 44 consecutive allogeneic PBSC collections performed between 1998 and 2009 in healthy pediatric donors in a single institution was done. Pediatric subjects were defined as less than 18 years old and less than 60 kg. Mobilization was with G-CSF (filgrastim) alone, given subcutaneously as 10 mcg/kg once daily (n=42), or 8 mcg/kg BID (n=2), for 5 consecutive days. Leukapheresis was initiated on day 5, at least 2 hours after the final G-CSF dose, using either the CS3000 (Fenwal) or Spectra (Gambro) cell separator. Central venous access was necessary in 29 of 44 subjects (66%). Donor demographics, self-reported ethnic backgrounds, and peripheral blood and component CD34+ cell counts were assessed at each procedure. All subjects were healthy siblings of patients undergoing hematopoietic transplantation for hematologic malignances, marrow failure syndromes, solid tumors, and congenital immune deficiencies. Donors gave assent/consent for participation in IRB-approved institutional protocols.
Donor age ranged from 3.8 to 17.8 years (mean 11.5 years), with 10 subjects (23%) under the age of 6 years, 15 (34%) between 7 and 12 years, and 19 (43%) between 12 and 17 years. Donor weight ranged from 16.1 to 59.1 kg (mean 38.6 kg). The cohort self-reported their ethnicity as 18 (41%) individuals being Hispanic, 16 (36%) Caucasian, 6 (13%) Black, and 3 (7%) Asian; 28 of 44 (63%) were female. G-CSF dose ranged from 7.6 to 16.7 mcg/kg, with 37 (84%) of the subjects receiving 9 to 13 mcg/kg (mean 10.2), and 6 (14%) receiving greater than 14 mcg/kg. Peak CD34+ count, assayed on a sample collected immediately prior to starting apheresis, was 75 ± 36 per mL (range 25 to 205/mL). A mean of 29.6 × 106 CD34+ cells (range 8.7 to 71.0) were harvested per liter processed, with 13.0 ± 5.4 liters processed per procedure (range 6.0 to 25.5 liters). In this manner, a total of 358 × 106 CD34+ cells (range 120–952 × 106) were collected per procedure, yielding a mean of 9.5 ×106 cells/kg recipient weight (range 3.17 to 20.8 ×106 cells/kg). Average procedural CD34+ collection efficiency was 57%. In univariate regression analysis, peak peripheral blood CD34+ counts on day 5 of G-CSF and CD34+ cell yields per liter processed during apheresis were significantly and negatively correlated with donor age (p=0.019), donor weight (p=0.011), and total CD34 dose (p=0.015). In contrast, peak circulating CD34+ counts were significantly higher in donors with higher baseline platelet (p=0.004) and mononuclear cell (p=0.027) counts. There was no significant relationship between donor gender or race and peak CD34+ mobilization response. In multivariate analysis, younger age was the single strongest factor associated with a favorable mobilization response (p=0.024); once age was in the model, donor weight and G-CSF dose no longer made significant contributions. In multivariate analysis, baseline platelet and mononuclear cell count (p=0.036 for both) continued to be strongly associated with a favorable mobilization response.
In a healthy allogeneic pediatric population with an age range of 3 to 17 years, younger age is the driving factor determining the peak CD34+ mobilization response to G-CSF. Younger donors were smaller (lower weight) and thus received lower total doses of filgrastim, resulting in an inverse relationship between G-CSF dose and mobilization response, an opposite finding to that seen in adult PBSC donors. Higher baseline platelets and mononuclear cell counts were also predictors of more robust mobilization responses. Our data suggest that mobilizable cell reserves are greater in very young subjects, and that higher G-CSF dose or larger apheresis volumes are not necessary to achieve targeted cell yields in this population.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.