Abstract 2145

Poster Board II-122

Introduction:

Plerixafor (AMD3100; PLX), a bicyclam molecule that reversibly inhibits binding of the CXCR4 chemokine receptor to stromal cell derived factor-1, is used clinically in combination with G-CSF for mobilization of hematopoietic stem cells. Although the effects of PLX plus G-CSF on mobilization of CD34+ cells have been well studied, the impact of PLX plus G-CSF on mobilization of lymphocytes and lymphocyte subsets remains unclear. Additionally, comparative effects of PLX on the content and subpopulations of lymphocytes in apheresis products from patients (pts) with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) have not been previously reported.

Patients and Methods:

Thirteen pts (7 NHL, 6 MM) underwent autologous PBSC mobilization with subcutaneous (sq) G-CSF (10 micrograms/kg/day x 4 days) and sq PLX (0.24 mg/kg on the fourth day of G-CSF administration), followed by large-volume apheresis approximately 15 hr after PLX dose. Pts who did not attain target CD34+ collection on first day of apheresis (day 1) received up to 3 additional daily doses of PLX plus G-CSF and up to 3 additional days of apheresis. Aliquots of apheresis products were obtained after each collection for differential WBC count, from which the absolute lymphocyte count (ALC) was calculated, and for flow cytometric quantitation of lymphocyte subsets. Cell doses were expressed per kg of pt weight. A nonparametric (Mann-Whitney) tests was used for all statistical analyses.

Results:

Five pts (1 NHL, 4 MM) collected target CD34+ cell doses (median 7.46 × 106 cells/kg; range, 7.22-22.7 × 106 cells/kg) with 1 apheresis. The remaining 8 pts collected target CD34+ cell doses after a total of 2 (2 NHL, 2MM), 3 (3 NHL) or 4 (1 NHL) aphereses. Doses of CD34+ cells, ALC, CD4+ cells, CD19+ cells and CD56+ cells were significantly higher in day 1 PBSC apheresis products from MM pts than from NHL pts, but neither CD3+ nor CD8+ cell dose was significantly different in the two groups (Table 1). For the pts undergoing 2 or more aphereses, comparison of day 1 and day 2 apheresis products showed significantly decreased doses of ALC, CD3+, CD4+ and CD8+ cells, but no significant differences in doses of CD34+, CD19+ or CD56+ cells (Table 2).

Table 1:

Cell Doses in Day 1 Apheresis Products after Mobilization with PLX plus G-CSF

Cell typeNHL (n=7)MM (n=6)P value
CD34 ×106/kg, Median (Range) 1.27 (0.78-11.0) 4.74 (1.43-22.7) 0.051 
ALC X108/kg, Median (Range) 3.58 (1.57-4.37) 5.15 (3.54-7.48) 0.035 
CD3 ×108/kg, Median (Range) 1.26 (0.63-2.40) 1.50 (1.07-3.97) NS 
CD4 ×108/kg, Median (Range) 0.55 (0.30-1.18) 0.97 (0.60-2.08) 0.035 
CD8 ×108/kg, Median (Range) 0.49 (0.24-0.97) 0.53 (0.18-1.76) NS 
CD19 ×108/kg, Median (Range) 0 (0-0.14) 0.14 (0-0.27) 0.035 
CD56 ×108/kg, Median (Range) 0.07 (0.03-0.12) 0.13 (0.12-0.54) 0.002 
Cell typeNHL (n=7)MM (n=6)P value
CD34 ×106/kg, Median (Range) 1.27 (0.78-11.0) 4.74 (1.43-22.7) 0.051 
ALC X108/kg, Median (Range) 3.58 (1.57-4.37) 5.15 (3.54-7.48) 0.035 
CD3 ×108/kg, Median (Range) 1.26 (0.63-2.40) 1.50 (1.07-3.97) NS 
CD4 ×108/kg, Median (Range) 0.55 (0.30-1.18) 0.97 (0.60-2.08) 0.035 
CD8 ×108/kg, Median (Range) 0.49 (0.24-0.97) 0.53 (0.18-1.76) NS 
CD19 ×108/kg, Median (Range) 0 (0-0.14) 0.14 (0-0.27) 0.035 
CD56 ×108/kg, Median (Range) 0.07 (0.03-0.12) 0.13 (0.12-0.54) 0.002 
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Table 2:

Effects of Second Apheresis on Cellular Composition of Autologous PBSCs Mobilized with PLX plus G-CSF

Cell typeDay 1 (n=7)Day 2 (n=7)P value
CD34 ×106/kg, Median (Range) 1.27 (0.78-2.26) 0.82 (0.58-1.89) NS 
ALC X108/kg, Median (Range) 3.54 (1.57-4.27) 1.95 (1.19-3.0) 0.017 
CD3 ×108/kg, Median (Range) 1.14 (0.63-2.40) 0.55 (0.15-0.93) 0.011 
CD4 ×108/kg, Median (Range) 0.60 (0.30-1.18) 0.22 (0.05-0.35) 0.007 
CD8 ×108/kg, Median (Range) 0.46 (0.24-0.97) 0.22 (0.07-0.47) 0.017 
CD19 ×108/kg, Median (Range) 0 (0-0.16) 0.001 (0-0.117) NS 
CD56 ×108/kg, Median (Range) 0.09 (0.04-0.54) 0.08 (0.04-0.30) NS 
Cell typeDay 1 (n=7)Day 2 (n=7)P value
CD34 ×106/kg, Median (Range) 1.27 (0.78-2.26) 0.82 (0.58-1.89) NS 
ALC X108/kg, Median (Range) 3.54 (1.57-4.27) 1.95 (1.19-3.0) 0.017 
CD3 ×108/kg, Median (Range) 1.14 (0.63-2.40) 0.55 (0.15-0.93) 0.011 
CD4 ×108/kg, Median (Range) 0.60 (0.30-1.18) 0.22 (0.05-0.35) 0.007 
CD8 ×108/kg, Median (Range) 0.46 (0.24-0.97) 0.22 (0.07-0.47) 0.017 
CD19 ×108/kg, Median (Range) 0 (0-0.16) 0.001 (0-0.117) NS 
CD56 ×108/kg, Median (Range) 0.09 (0.04-0.54) 0.08 (0.04-0.30) NS 
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Conclusions:

PLX plus G-CSF effectively mobilizes lymphocytes and lymphocyte subsets as well as CD34+ cells. Pts with MM had significantly higher doses of specific lymphocyte subsets, notably CD4+ and CD56+, than did pts with NHL, potentially reflecting differences in previous treatments (e.g., lenalidomide plus dexamethasone in MM pts compared with ICE or ESHAP in NHL pts). These findings are relevant to the understanding of the effects of infused lymphocyte subsets on outcomes of and immune reconstitution after autologous PBSC transplantation.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
apheresis, granulocyte colony-stimulating factor, lymphocyte subset, peripheral blood stem cells, plerixafor, recombinant granulocyte colony stimulating factor, brachial plexus neuritis, cd19 antigens, cd34 antigens, cd56 antigens

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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