Impact of good and poor mobilizers on hematopoietic progenitor cell collection efficiency and product quality

2018 ◽  
Vol 34 (1) ◽  
pp. 39-43
Author(s):  
Abdel-Ghani M. Azzouqa ◽  
Kinda Jouni ◽  
Vivek Roy ◽  
Abba C. Zubair
2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S34-S35
Author(s):  
Aidas Mattis ◽  
Diane Sempek ◽  
Suzanne Thibodeaux

Abstract Hematopoietic progenitor cell (HPC) transplant product quality indicators after prolonged cryopreservation are variable. A recent study in Europe demonstrated wide variability of cryopreservation times, from 1 to >20 years, with most centers storing products for 5 or 10 years. Thawed HPC viability using various ex vivo means and in vivo by studying neutrophil and platelet engraftment has generally supported preservation of CD34+ viability with prolonged storage. However, sample size, methods, and timepoints varied, and clear guidelines currently do not exist regarding how long HPCs can be stored. This study’s objectives include an evaluation of HPC quality indicators over time and if HPC product age and/or viability correlates with HPC engraftment. Retrospective record review was conducted on 837 HPC products thawed between January 1, 2011, and December 31, 2018. HPC products were sampled and characterized at thawing by flow cytometry for total nucleated cell (TNC) recovery, CD34+ recovery, and CD34+ viability (by 7-AAD). Preestablished acceptability criteria for TNC recovery, CD34+ recovery, and CD34+ viability were >80%, >40%, and >60%, respectively. If available, products with ANC engraftment data were further analyzed to correlate data with time to HPC engraftment. HPC products were stored between 3 and 5,943 days; 816 products were infused, ranging from 3 to 5,273 days in storage. Most (81%) HPC transplants occurred within the first year, 47 infusions occurred after storage >5 years, and 4 infusions occurred after storage >10 years. CD34 viability and percent recovery of TNC and CD34 were not significantly different as time in storage increased. Given sample paucity, 19 samples stored for >10 years were analyzed in individual years and grouped. In total, 96.5% samples stored for <1 year and 68% in samples stored >10 years met acceptability criteria for >60% CD34+ recovery; 98.9% samples stored <1 year met the >60% CD34+ viability acceptability threshold versus 90% of samples stored for >10 years. The oldest sample infused after storage of 5,273 days (14.4 years) showed 42% TNC recovery, 19% CD34+ recovery, and 84% CD34 viability; ANC engraftment data were not available. Sixty-five samples containing ANC engraftment data showed that time to ANC engraftment ranged from 9 to 15 days. No clear trend was present for viability or CD34 recovery when compared with days to engraftment based on limited data. Although rare, infusion of HPC products of extended duration occurs. This study suggests that HPC product quality may decrease after extended cryopreservation based on preestablished acceptability criteria. The oldest sample infused had preserved CD34+ viability despite significantly less TNC and CD34+ recovery, suggesting thawing might select for more robust HPCs. More studies with older samples are needed to determine the clinical impact of cryopreservation and if modification of current quality indicators could be useful clinically.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18576-e18576
Author(s):  
Bijay Nair ◽  
Sarah Waheed ◽  
Gary Villines ◽  
Frits Van Rhee ◽  
Saad Zafar Usmani ◽  
...  

e18576 Background: Currently available agents such as cyclophosphamide or etoposide in combination with G-CSF and plerixafor are effective in mobilizing HPC in most patients with myeloma and refractory lymphoma needing autologous HPC transplant. Unfortunately, there are patients who are unable to mobilize HPC adequately because of prior radiation or stem cell toxic alkylating chemotherapy. As Thom et al. noted an increase in circulating CD34+ cells in patients undergoing hyperbaric oxygen therapy (HBOT) for osteoradionecrosis of the mandible, we examined this modality as a mobilizing agent in those who failed at least one other modality. Methods: A retrospective data review of all patients undergoing HPC mobilization from January 2009 to December 2011 identified 9 patients (7 male, 2 female), (8 multiple myeloma, 1 non-Hodgkin lymphoma) who underwent HBOT for mobilization of HPC after failing to collect at least 2 x 10e6 CD34+ cells/kg CD34 cells/kg body weight following standard mobilization using chemotherapy, G-CSF and/or plerixafor. Mean age was 61 (range 52-82 y). Four had previously undergone autologous transplant. Treatment was in hyperbaric oxygen chambers pressurized with 100% oxygen at 1.5 atmospheres of pressure for 90 minutes per day, with treatment ranging from 3 to 8 days. During this period patients also received growth factors and plerixafor. Results: Total CD34+ cells/kg collected ranged from 0.1 - 20.6 x 10e6 CD34+ cells/kg; 5 patients collected > 2 x 10e6 CD34+ cells/kg, of which 3 collected > 5 x 10e6 CD34+ cells/kg. All patients had failed prior mobilization and collection with G-CSF, and 8 had also previously received plerixafor. One of the patients who had undergone prior tandem transplant collected 8.23 x10e6 CD34+ cells/kg. No patient experienced toxicities known to be associated with use of HBOT such as barotrauma. Conclusions: HBOT appears to be an effective and safe modality to mobilize HPC in patients who are poor mobilizers, when used in conjunction with G-CSF and plerixafor.


Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4060-4066 ◽  
Author(s):  
Maria Fiammetta Romano ◽  
Annalisa Lamberti ◽  
Rita Bisogni ◽  
Corrado Garbi ◽  
Antonio M. Pagnano ◽  
...  

Abstract We investigated the involvement of NF-κB/Rel transcription factors that reportedly can inhibit apoptosis in various cell types in the antiapoptotic mechanism of the cytoprotectant amifostine. In the nontumorigenic murine myeloid progenitor 32D cells incubated with amifostine, we detected a reduction of the IκB cytoplasmic levels by Western blotting and a raising of nuclear NF-κB/Rel complexes by electrophoretic mobility shift assay. Amifostine inhibited by more than 30% the growth factor deprivation-induced apoptosis, whereas its effect failed when we blocked the NF-κB/Rel activity with an NF-κB/Rel-binding phosphorothioate decoy oligodeoxynucleotide. In human cord blood CD34+ cells, the NF-κB/Rel p65 subunit was detectable (using immunofluorescence analysis) mainly in the cytoplasm in the absence of amifostine, whereas its presence was appreciable in the nuclei of cells incubated with the cytoprotectant. In 4 CD34+ samples incubated for 3 days in cytokine-deficient conditions, cell apoptosis was reduced by more than 30% in the presence of amifostine (or amifostine plus a control oligo); the effect of amifostine was abolished in cultures with the decoy oligo. These findings indicate that the inhibition of hematopoietic progenitor cell apoptosis by amifostine requires the induction of NF-κB/Rel factors and that the latter can therefore exert an antiapoptotic activity in the hematopoietic progenitor cell compartment. Furthermore, the identification of this specific mechanism underlying the survival-promoting activity of amifostine lends support to the possible use of this agent in apoptosis-related pathologies, such as myelodysplasias.


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