Timing of Peripheral Blood Stem Cell Yield: Comparison of Alternative Methods with the Classic Method for CD34⁺Cell Determination

Abstract

Hematopoietic stem cells (HSCs), still represent a certain mystery in biology, have a unique property of dividing into equal cells and repopulating the hematopoietic tissue. This potential enables their use in transplantation treatments. The quality of the HSC grafts for transplantation is evaluated by flow cytometric determination of the CD34+ cells, which enables optimal timing of the first apheresis and the acquisition of maximal yield of the peripheral blood stem cells (PBSCs). To identify a more efficient method for evaluating CD34+ cells, we compared the following alternative methods with the reference method: hematopoietic progenitor cells (HPC) enumeration (using the Sysmex XE-2100 analyser), detection of CD133+ cells, and quantification of aldehyde dehydrogenase activity in the PBSCs. 266 aphereses (84 patients) were evaluated. In the preapheretic blood, the new methods produced data that were in agreement with the reference method. The ROC curves have shown that for the first-day apheresis target, the optimal predictive cut-off value was 0.032 cells/mL for the HPC method (sensitivity 73.4%, specificity 69.3%). HPC method exhibited a definite practical superiority as compared to other methods tested. HPC enumeration could serve as a supplementary method for the optimal timing of the first apheresis; it is simple, rapid, and cheap.

Algorithms utilizing peripheral blood hematopoietic progenitor cell counts in lieu of some CD34+ cell counts predict successful peripheral blood stem cell collections with substantial time and cost savings

“…Several groups have demonstrated reasonably good correlations between HPC counts and PB CD34 counts . Algorithms to guide PBSC collections using HPC counts have been proposed for certain patient populations . However, very few of these algorithms have been tested prospectively, and none addressed when to begin large volume PBSC collections in chemomobilized patients, or whether HPC values could be used to guide administration of plerixafor to optimize PBSC collections in cytokine‐mobilized patients who would be predicted to otherwise collect poorly.…”

“…The use of HPC to predict PB CD34+ cell counts and potentially guide PBSC collection has been proposed in the literature multiple times over the past two decades. Several groups have demonstrated reasonably good correlations between HPC counts and PB CD34 counts . Algorithms to guide PBSC collections using HPC counts have been proposed for certain patient populations .…”

“…HPC measurement saves considerable time and money when compared with conventional CD34+ measurements . Based on reasonably good correlations between HPC counts and successful PBSC collections, several groups proposed algorithms from retrospective data that utilized HPC counts rather than CD34+ counts to guide PBSC collection strategies . Two studies prospectively validated their cutpoints; however, they studied only chemomobilized patients, and their outcomes were defined as successfully reaching the total product yield needed for PBSCT in a series of aphereses.…”

Method comparison study of peripheral blood CD34+ count performed on an Abbott CELL-DYN Sapphire hematology analyzer versus flow cytometry reference procedure (modified ISHAGE)

“…G-CSF stimulation results in an increase of white blood cell (WBC) counts including a variable increase in circulating HPCs. Enumeration of circulating CD34+ cells in mobilized donors and patients is considered to be the best predictor of a successful HPC(A) collection 4 .…”

“…The current recommended method for CD34+ cell enumeration by the International Society of Hematotherapy and Graft Engineering (ISHAGE) utilizes clinical flow cytometry instrumentation and sophisticated data analysis protocols 4 . The availability of this type of specialized testing is usually limited to routine clinical laboratory day shifts (Monday to Friday, 9AM – 5PM) whereas other clinical laboratories such as Hematology are available to perform testing 7 days a week, 24 hours a day.…”