Pediatric Peripheral Blood Stem Cell Research Articles

Alemtuzumab, Dual Graft-versus-Host Disease Prophylaxis, and Lower CD3+ T Cell Doses Equalize Rates of Acute and Chronic Graft-versus-Host Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation with Matched Unrelated Donor Peripheral Blood Stem Cells or Bone Marrow Grafts

Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based conditioning are lacking. We investigated whether in vivo T cell depletion using alemtuzumab could reduce the risk of severe acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) after HSCT with matched unrelated donor (MUD) BM or PBSCs. This retrospective multicenter study included 397 children (BM group, n = 202; PBSC group, n = 195) who underwent first MUD HSCT at 9 pediatric centers in the United Kingdom between 2015 and 2019. The median age at transplantation was 7.0 years (range, .1 to 19.3 years), and the median duration of follow-up was 3.1 years (range, .3 to 7.5 years). The 3-year overall survival was 81% for the entire cohort (BM group, 80%; PBSC group, 81%). The incidence of grade II-IV aGVHD was significantly higher in the PBSC group (31%) compared to the BM group (31% versus 19%; P = .003), with no difference in the incidence of grade III-IV aGVHD (BM, 7%; PBSC, 12%; P = .17). CD3+ T cell dose >5 × 108/kg and the use of PBSCs were independent predictors of grade II-IV aGVHD. When considering CD3+ T cell dose and GVHD prophylaxis, PBSC transplantation with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) and a CD3+ T cell dose ≤5 × 108/kg had a comparable grade II-IV aGVHD to BM transplantation plus a CNI (20% versus 18%; P = .52). PBSC transplantation was associated with a lower incidence of cGVHD compared to BM transplantation (6% versus 11%; P = .03). Within the limits of this study, we identified a potential strategy to reduce the risk of severe GVHD in pediatric PBSC recipients that includes a combination of in vivo T cell depletion using alemtuzumab and dual GVHD prophylaxis (with a CNI and MMF) and limiting the CD3+ T cell dose to ≤5 × 108/kg.

Safety of Pediatric Peripheral Blood Stem Cell Harvest in Daycare Setting: An Institutional Experience.

Introduction:Children serving as a donor for their siblings will require anesthesia or sedation. In view of shortage of time and space in operating room setting, peripheral blood stem cell (PBSC) harvest is performed as a daycare procedure.Aim:This study aims to find out whether performing PBSC harvest in hematology blood collection area as a daycare procedure is safe or not.Settings and Design:This secondary analysis included 164 pediatric PBSC harvest (154 pediatric donors, of which 10 had repeat harvesting done) donors, performed under anesthesia, in the Department of Hematology, between January 2009 and June 2017.Materials and Methods:Donors were examined, informed consent was obtained, and adequate premedications were ensured. Induction was intravenous for cooperative donors or inhalational sevoflurane followed by intravenous maintenance infusion using either face mask or a laryngeal mask airway (LMA). During the procedure, vitals are monitored with a noninvasive monitor. Normal hemodynamics were ensured before transferring the children to the ward.Statistical Analysis:Statistical analysis was performed using SPSS 16.0 statistical software. Descriptive statistics and frequencies were used for the data description.Results:A total of 137 donors (median age of 5 years) were induced with sevoflurane and LMA was used in 84 children and face mask in 53. Twenty-seven children cooperated for intravenous induction. Various combinations of propofol, dexmedetomidine, and ketamine were used with respiratory and hemodynamic stability. The median duration of anesthesia was 250 (165–375) min. The recovery from anesthesia was smooth with a median wake-up time of 20 (5–60) min.Conclusion:This retrospective analysis demonstrates that nonoperating room anesthesia for pediatric age group for PBSC harvest can be safely and successfully accomplished outside the operation room setting by a consultant anesthesiologist.

Analysis of Donor Demographic and Laboratory Parameters Affecting CD34+ Cell Mobilization In Healthy Allogeneic Pediatric Peripheral Blood Stem Cell (PBSC) Donors

AbstractAbstract 2259 Background: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. Methods: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. Results: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. Conclusions: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. Disclosures:No relevant conflicts of interest to declare.

Development of an educational brochure for pediatric peripheral blood stem cell collection

Development of an educational brochure for pediatric peripheral blood stem cell collection

Development of an Educational Brochure for Pediatric Peripheral Blood Stem Cell Collection

Development of an Educational Brochure for Pediatric Peripheral Blood Stem Cell Collection