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Mobilization with cyclophosphamide reduces the number of lymphocyte subpopulations in the leukapheresis product and delays their reconstitution after autologous hematopoietic stem cell transplantation in patients with multiple myeloma

View Article: PubMed Central - PubMed

ABSTRACT

Background: Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation.

Patients and methods: In total 48 patients were prospectively enrolled in three different mobilization regimens; (i) filgrastim (20), (ii) pegfilgrastim (19) and (iii) cyclophosphamide + filgrastim (9). Lymphocytes, CD16+/56+ natural killer and CD4+/CD25high T regulatory cells were determined by flow cytometry.

Results: We found a statistically significant difference between the mobilization regimens. Cyclophosphamide reduced lymphocyte and natural killer (NK) cell counts on collection day (lymphocytes 1.08 × 109/L; NK cells 0.07 × 109/L) compared to filgrastim (lymphocytes 3.08 × 109/L; NK cells 0.52 × 109/L) and pegfilgrastim (lymphocytes 3 × 109/L; NK cells 0.42 × 109/L). As a consequence lymphocyte and NK cell counts were also lower in the leukapheresis products following cyclophosphamide mobilization regimen (lymphocytes 50.1 × 109/L; NK cells 4.18 × 109/L) compared to filgrastim (lymphocytes 112 × 109/L; NK cells 17.5 × 109/L) and pegfilgrastim (lymphocytes 112 × 109/L; NK cells 14.3 × 109/L). In all mobilization regimens T regulatory cells increased 2-fold on collection day, regarding the base line value before mobilization. There was no difference in T regulatory cell counts between the regimens.

Conclusions: Mobilization with cyclophophamide reduces the number of mobilized and collected lymphocytes and NK cells as compared to mobilization with growth factors only and results in their delayed reconstitution following autologous hematopoietic stem cell transplantation. We found no difference between filgrastim and pegfilgrastim mobilization.

No MeSH data available.


The mean lymphocyte, natural killer (NK) cell and Treg cell counts (109/L) before mobilization and on collection day with 95 % confidence interval (CI) for mobilization with cyclophosphamide (cyclo), pegfilgras tim (pegG-CSF) and filgrastim (G-CSF).
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j_raon-2016-0028_fig_001: The mean lymphocyte, natural killer (NK) cell and Treg cell counts (109/L) before mobilization and on collection day with 95 % confidence interval (CI) for mobilization with cyclophosphamide (cyclo), pegfilgras tim (pegG-CSF) and filgrastim (G-CSF).

Mentions: No differences between the three regimens were noted in lymphocyte, NK cell and Treg cell counts before mobilization. Mobilization with cyclophosphamide reduced the lymphocyte and NK cell counts on collection day by 2-fold as compared to baseline value before mobilization. On the contrary mobilization with G-CSF and pegfligrastim induced a 2- fold increase in lymphocyte and NK cell counts on collection day as compared to baseline value before mobilization (Figure 1). This resulted in different lymphocyte and NK cell counts on collection day between the mobilization regimens (p < 0.001). In pairwise comparison the differences between mobilization with cyclophosphamide and G-CSF only, and cyclophosphamide and pegfilgrastim only were statistically significant (p < 0.001). The differences in lymphocyte and NK cell counts on collection day resulted in a significantly different lymphocyte and NK cell composition of the leukapheresis product (Table 2). All three mobilization regimens increased Treg cell counts on collection day by 2-fold with no differences in absolute values between the three regimens. Comparison between the groups mobilized with G-CSF or pegfilgrastim showed no difference in lymphocyte, NK and Treg cell counts on the collection day, in the leukapheresis product and on day 15 after AHSCT. Because no difference in lymphocyte and NK cell counts during mobilization and in the leukapheresis product was noted between the G-CSF and pegfilgrastim group, and due to the small patient sample, we analyzed lymphocyte counts on day 15 after AHSCT between cyclophosphamide mobilization and growth factors only (G-CSF and pegfilgrastim combined) mobilization. Mobilization with growth factors resulted in a higher lymphocyte count on day 15 post AHSCT compared to cyclophosphamide mobilization (p < 0.04).


Mobilization with cyclophosphamide reduces the number of lymphocyte subpopulations in the leukapheresis product and delays their reconstitution after autologous hematopoietic stem cell transplantation in patients with multiple myeloma
The mean lymphocyte, natural killer (NK) cell and Treg cell counts (109/L) before mobilization and on collection day with 95 % confidence interval (CI) for mobilization with cyclophosphamide (cyclo), pegfilgras tim (pegG-CSF) and filgrastim (G-CSF).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5120577&req=5

j_raon-2016-0028_fig_001: The mean lymphocyte, natural killer (NK) cell and Treg cell counts (109/L) before mobilization and on collection day with 95 % confidence interval (CI) for mobilization with cyclophosphamide (cyclo), pegfilgras tim (pegG-CSF) and filgrastim (G-CSF).
Mentions: No differences between the three regimens were noted in lymphocyte, NK cell and Treg cell counts before mobilization. Mobilization with cyclophosphamide reduced the lymphocyte and NK cell counts on collection day by 2-fold as compared to baseline value before mobilization. On the contrary mobilization with G-CSF and pegfligrastim induced a 2- fold increase in lymphocyte and NK cell counts on collection day as compared to baseline value before mobilization (Figure 1). This resulted in different lymphocyte and NK cell counts on collection day between the mobilization regimens (p < 0.001). In pairwise comparison the differences between mobilization with cyclophosphamide and G-CSF only, and cyclophosphamide and pegfilgrastim only were statistically significant (p < 0.001). The differences in lymphocyte and NK cell counts on collection day resulted in a significantly different lymphocyte and NK cell composition of the leukapheresis product (Table 2). All three mobilization regimens increased Treg cell counts on collection day by 2-fold with no differences in absolute values between the three regimens. Comparison between the groups mobilized with G-CSF or pegfilgrastim showed no difference in lymphocyte, NK and Treg cell counts on the collection day, in the leukapheresis product and on day 15 after AHSCT. Because no difference in lymphocyte and NK cell counts during mobilization and in the leukapheresis product was noted between the G-CSF and pegfilgrastim group, and due to the small patient sample, we analyzed lymphocyte counts on day 15 after AHSCT between cyclophosphamide mobilization and growth factors only (G-CSF and pegfilgrastim combined) mobilization. Mobilization with growth factors resulted in a higher lymphocyte count on day 15 post AHSCT compared to cyclophosphamide mobilization (p < 0.04).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation.

Patients and methods: In total 48 patients were prospectively enrolled in three different mobilization regimens; (i) filgrastim (20), (ii) pegfilgrastim (19) and (iii) cyclophosphamide + filgrastim (9). Lymphocytes, CD16+/56+ natural killer and CD4+/CD25high T regulatory cells were determined by flow cytometry.

Results: We found a statistically significant difference between the mobilization regimens. Cyclophosphamide reduced lymphocyte and natural killer (NK) cell counts on collection day (lymphocytes 1.08 &times; 109/L; NK cells 0.07 &times; 109/L) compared to filgrastim (lymphocytes 3.08 &times; 109/L; NK cells 0.52 &times; 109/L) and pegfilgrastim (lymphocytes 3 &times; 109/L; NK cells 0.42 &times; 109/L). As a consequence lymphocyte and NK cell counts were also lower in the leukapheresis products following cyclophosphamide mobilization regimen (lymphocytes 50.1 &times; 109/L; NK cells 4.18 &times; 109/L) compared to filgrastim (lymphocytes 112 &times; 109/L; NK cells 17.5 &times; 109/L) and pegfilgrastim (lymphocytes 112 &times; 109/L; NK cells 14.3 &times; 109/L). In all mobilization regimens T regulatory cells increased 2-fold on collection day, regarding the base line value before mobilization. There was no difference in T regulatory cell counts between the regimens.

Conclusions: Mobilization with cyclophophamide reduces the number of mobilized and collected lymphocytes and NK cells as compared to mobilization with growth factors only and results in their delayed reconstitution following autologous hematopoietic stem cell transplantation. We found no difference between filgrastim and pegfilgrastim mobilization.

No MeSH data available.