Introduction In clinical practice, a hematopoietic progenitor cell (HPC) dose of 2 million CD34+ cells/kg is the desired minimum needed for timely neutrophil and platelet (PLT) engraftment in autologous hematopoietic… Click to show full abstract
Introduction In clinical practice, a hematopoietic progenitor cell (HPC) dose of 2 million CD34+ cells/kg is the desired minimum needed for timely neutrophil and platelet (PLT) engraftment in autologous hematopoietic cell transplantation (HCT). Patients frequently receive higher HPC doses with the median pre-cryopreservation dose at our center being 5 million CD34+ cells/kg adjBW25%. Cryopreservation (CP) and thawing leads to cell loss through mechanisms including activation of the caspase pathway. The degree of loss in post-CP HPC doses can range from 20 to 85%; hence the cell dose that is able to effectuate engraftment is determined by the percentage of surviving cells in the initial pre-CP cell dose. This effective residual vital dose (ERVD) is the product of the pre-CP cell dose and the post thaw viability percentage. Objective Correlate viability, HPC cell dose and the ERVD to engraftment. Method We conducted a retrospective review of autologous HCT patients at our center to correlate the ERVD with engraftment. Twenty-five patients, ages 32 to 76, receiving 27 transplants had HPC infusions during 1 or 2 sessions within 3 days of each other. Diagnoses were multiple myeloma (MM) (n=20) and lymphoma (n=7). Engraftment of neutrophils and PLTs was defined using CIBMTR definitions. Viability was assessed by 7AAD on CD34+ cells. Data was analyzed with Excel Correlation Function which calculates the Pearson Product-Moment Correlation Coefficient for 2 sets of values. Results The median neutrophil and PLT engraftment times were 11 and 16.5 days, respectively. Correlation of the HPC dose of the total population with neutrophil engraftment data, revealed the r value to be -0.31 for all patients, -0.20 for lymphoma patients, and -0.32 for MM patients. Cell dose correlation with PLT engraftment revealed the r value to be -0.43 for the total population (Figure 1), -0.52 for the lymphoma subset, and -0.55 for the MM subset. We found a moderately strong correlation of ERVD with PLT engraftment with an r value of -0.56 for the entire population, i.e. as ERVD increased, time to PLT engraftment decreased (Figure 2). When separated by diagnosis (MM vs lymphoma) the ERVD correlated moderately with PLT engraftment, r value of -0.57 amongst the MM subset and -0.88 for the lymphoma subset (Figure 3). Neutrophil engraftment had a weaker correlation with the ERVD, r value of -0.33 for the entire population, -0.41 for the MM subset, and -0.68 for the lymphoma subset. Conclusion Based on our data, the ERVD has a moderately strong correlation with PLT and neutrophil engraftment in a population of MM and lymphoma patients undergoing autologous HCT. The correlation was stronger for PLT engraftment and strongest amongst patients with lymphoma. To achieve our median engraftment times for neutrophils and PLTs the optimal ERVD of approximately 3 Million CD34/Kg adjBW25% is suggested.
               
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