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 >90%). All patients received G-CSF after stem cell infusion: from day 0 in <10% and from day +5 in >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 (106/kg IBW)

CD34+ cell dose CD34+ cell dose 
≤3 42 >3 712 
≤4 109 >4 645 
≤5 260 >5 494 
≤6 434 >6 320 
≤7 534 >7 220 
≤8 586 >8 168 
≤9 619 >9 135 
≤10 646 >10 108 
≤15 714 >15 40 
CD34+ cell dose CD34+ cell dose 
≤3 42 >3 712 
≤4 109 >4 645 
≤5 260 >5 494 
≤6 434 >6 320 
≤7 534 >7 220 
≤8 586 >8 168 
≤9 619 >9 135 
≤10 646 >10 108 
≤15 714 >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/>3 0.28 0.003 0.083 0.43 
≤4/>4 0.029 0.0007 0.027 0.39 
≤5/>5 0.002 0.001 0.0004 0.031 
≤6/>6 <0.0001 <0.0001 0.002 0.076 
≤7/>7 <0.0001 <0.0001 0.0002 0.009 
≤8/>8 <0.0001 <0.0001 0.0002 0.006 
≤9/>9 <0.0001 <0.0001 0.0004 0.005 
≤10/>10 <0.0001 <0.0001 <0.0001 0.006 
≤15/>15 0.005 0.001 0.003 0.004 
CD34+ cell dose bands ANC 0.5 ANC 1.0 PLT 20 PLT 50 
≤3/>3 0.28 0.003 0.083 0.43 
≤4/>4 0.029 0.0007 0.027 0.39 
≤5/>5 0.002 0.001 0.0004 0.031 
≤6/>6 <0.0001 <0.0001 0.002 0.076 
≤7/>7 <0.0001 <0.0001 0.0002 0.009 
≤8/>8 <0.0001 <0.0001 0.0002 0.006 
≤9/>9 <0.0001 <0.0001 0.0004 0.005 
≤10/>10 <0.0001 <0.0001 <0.0001 0.006 
≤15/>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.

Disclosures: No relevant conflicts of interest to declare.

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