The Effect of Increasing CD34+ Cell Doses on Time to Engraftment after Autotransplantation for Hematologic Malignancies.
Authors: Singh V. , Krishnamurthy J. , Frankfurt O. , Evens Andrew M , Altman J. , Gordon L. , Singhal S. , Tallman M. , Williams S. , Winter J. , Mehta J. 
Published: April 2020

Abstract
It is thought that 2 x 106/kg is the minimum CD34+ cell dose needed for autotransplantation, while the ideal dose is generally accepted to be 5 x 106/kg. Whether infusing cell doses higher than 5 x 106/kg offers additional benefit is unknown. The relationship between time to standard engraftment endpoints (0.5 x 109/L Neutrophils – ANC 0.5, 1 x 109/L neutrophils – ANC 1.0, 20 x 109/L platelets – PLT 20, and 50 x 109/L platelets – PLT 50) and the CD34+ cell doses infused was explored in 754 autografts performed for malignant diseases in adult patients: 32 leukemia, 195 lymphoma, 514 myeloma, 13 other. The conditioning regimens used were standard (high-dose melphalan, BEAM, busulfan-cyclophosphamide, or busulfan-etoposide in &gt;90%). All patients received G-CSF after stem cell infusion: from day 0 in &lt;10% and from day +5 in &gt;90%. Cell dose calculations were based upon ideal body weight. Table 1 shows the distribution of the CD34+ cell ranges infused.
Table 1: CD34+ cell numbers infused (10 6 /kg IBW)
CD34+ cell dose n CD34+ cell dose n ≤3 42 &gt;3 712 ≤4 109 &gt;4 645 ≤5 260 &gt;5 494 ≤6 434 &gt;6 320 ≤7 534 &gt;7 220 ≤8 586 &gt;8 168 ≤9 619 &gt;9 135 ≤10 646 &gt;10 108 ≤15 714 &gt;15 40
Figure 1 shows the mean days to achieving the 4 engraftment endpoints under study by the number of CD34+ cells infused. It is clear that increasing CD34+ cell doses hasten platelet recovery significantly through the entire range of CD34+ cell dose ranges studied. Increasing CD34+ cell doses appear to hasten neutrophil recovery too, but the benefit seems to level off beyond 10 x 106 CD34+ cells per kg. The effect of a CD34+ cell dose of ≤2 x 106/kg was not analyzed because only 7 patients received this small quantity of cells.
Figure 1: The effect of different CD34+ cell dose ranges on various engraftment endpoints Figure 1: . The effect of different CD34+ cell dose ranges on various engraftment endpoints
The relationship between CD34+ cell doses and engraftment holds true even when the data are analyzed in a dichotomous fashion as shown in Figure 2.
Figure 2: Differences in engraftment based upon CD34+ cell doses Figure 2: . Differences in engraftment based upon CD34+ cell doses
CD34+ cell dose bands ANC 0.5 ANC 1.0 PLT 20 PLT 50 ≤3/&gt;3 0.28 0.003 0.083 0.43 ≤4/&gt;4 0.029 0.0007 0.027 0.39 ≤5/&gt;5 0.002 0.001 0.0004 0.031 ≤6/&gt;6 &lt;0.0001 &lt;0.0001 0.002 0.076 ≤7/&gt;7 &lt;0.0001 &lt;0.0001 0.0002 0.009 ≤8/&gt;8 &lt;0.0001 &lt;0.0001 0.0002 0.006 ≤9/&gt;9 &lt;0.0001 &lt;0.0001 0.0004 0.005 ≤10/&gt;10 &lt;0.0001 &lt;0.0001 &lt;0.0001 0.006 ≤15/&gt;15 0.005 0.001 0.003 0.004
Table 2 shows the significance of the differences illustrated in Figure 2.
Table 2: Significance of differences in time to engraftment
These data suggest that increasing CD34+ cell numbers hasten hematologic recovery – even beyond a cell dose of 15 x 106/kg. It remains to be seen if more rapid engraftment resulting from infusion of higher number of CD34+ cells results in practical benefits such as more robust/durable engraftment, decreased toxicity, and improved survival.