Potentially modifiable predictors of cell collection efficiencies and product characteristics of allogeneic hematopoietic progenitor cell collections

Abstract

Background Hematopoietic progenitor cell (HPC) and immune effector cell (IEC) therapies often require high doses of mononuclear cells (MNCs), whether CD34+ cells, lymphocytes, or monocytes. Cells for IEC can be sourced from HPC products. We thus examined potentially modifiable variables affecting collection efficiencies (CEs) of MNC subsets in HPC collection and also of the typically undesired cell types of platelets, granulocytes, and red cells, which hinder downstream processing. Finally, we sought to confirm previously indeterminate studies of the effect of an adjusted collect flow rate (CFR) on CD34+ CE. Study Design and Methods We performed univariate and multivariate regression analyses of all 135 National Marrow Donor Program (NMDP) HPC collections in 2019 and compared these fixed CFR procedures to previous NMDP collections using adjusted CFRs. Results Target cell CEs decreased with increasing peripheral blood (PB) concentration and were associated with different cell type locations within the MNC layer. CEs of undesired cell types varied with standard procedural parameters (inlet flow rate, whole blood processed, etc.). Interestingly, some CEs increased with preapheresis hematocrit. Finally, adjusting the CFR by PB MNC count improved MNC CE but not CD34+ CE. Conclusion Correlation of target cell CEs with their PB concentration and different cell type locations by depth within the MNC layer indicates the importance of investigating the compensatory fine‐tuning of procedure variables to improve CE. Correlation of CEs with PB hematocrit, and CFR adjustment by a modified PB MNC and/or PB CD34 algorithm should be further explored. Adjusting standard procedural parameters may reduce product contamination.

Process and procedural adjustments to improve CD34+ collection efficiency of hematopoietic progenitor cell collections in sickle cell disease

“…1,5,6 Second, the number of donor TBV equivalent to the absolute liters that must be processed to reach the CD34+ collection target must be considered, due to the variation in donor absolute liters equal to one TBV. Third, CD34+ CE is inversely related to pre-apheresis PB CD34+ count, 7 as was observed in our two patients, with patient #1 having a CD34+ CE1 of 70% versus 51% in patient #2, resulting in a greater CD34+ fold decrease per TBV processed in patient #1 versus #2 (27% vs. 12%). Therefore, with high pre-apheresis CD34 counts, prolonging collection is worthwhile despite low CD34+ CEs, given that counts may still be elevated 11-12 h post-plerixafor 18 even with ongoing collection.…”

“…1,31 Using the Sysmex XN (Sysmex, Lincolnshire, IL) hematology analyzer, the two product Hcts of 6.1% and 7.6% were higher than the historical mean of 3% ± 3% 10 for HPC products in donors without SCD, but were similar to means with another hematology analyzer. 2,7 We also had similar recovery and purity with immunomagnetic CD34+ selection (Miltenyi CliniMACS, Miltenyi Biotec, Auburn, CA) as with our patients without SCD. 31…”

“…We are currently further examining the utility of adjusting the CFR based on a MNC count, rather than WBC-based algorithm in normal donors. 7 Notably, if such an algorithm had been used here, the CFR would have been approximately 1.5 ml/min for patient #1 and 1.2 ml/min for patient #2. We and others 4,6 also collected at a slightly deeper Hct of the second to last color bar on the Terumo collection preference tool (approx.…”

“…Factors that contribute to poor CD34+ CEs and unstable interfaces in SCD remain unclear, and there are multiple potentially modifiable variables that may affect CD34+ CE. 7 Chronic simple transfusion or RBC exchange (RCE) for several months prior to mobilization and collection is standard, but may not result in improvement in SCD-related inflammation. 8 In patients conditioned with RCE, CD34+ CE and total yield do not correlate with HbS% level.…”

“…10 In our analysis of 135 healthy allogeneic donor HPC products collected using the Optia CMNC and analyzed with the Ac_T 5diff AL hematology analyzer (Beckman Coulter, Brea, CA), the mean product Hct was 6.3% ± 2.0%. 7 We hypothesized that variables specific to SCD that might contribute to unstable interfaces and poor CD34+ CE include activation of blood cells 11,12 and elevated viscosity. 13 For example, platelet clumping may contribute to unstable interfaces and thus lower CD34+ CE.…”