The Impact of Lymphocyte Composition in the Stem Cell Harvest on Blood Lymphocytes 1-2 Weeks Post-Autologous Stem Cell Transplant for Newly Diagnosed Myeloma

Abstract

Background It is known that cellular composition of the stem cell harvest in autologous stem cell transplantation for multiple myeloma is important for engraftment and blood reconstitution, with CD34 count commonly used as a marker for harvest adequacy; however, there is a relative lack of data on the importance of lymphocyte marker-expressing cells in the harvest and their implications for immune reconstitution and outcome. Here, we demonstrate that the amount and proportion of lymphocyte marker-expressing cells in the stem cell harvest directly correlate with the cellular composition of the peripheral blood 1-2 weeks post-transplant. Objective To investigate whether the immunological cellular composition of the stem cell harvest prior to autologous stem cell transplantation in multiple myeloma correlates with the cellular composition of peripheral blood 1-2 weeks post-transplant. Methods We analysed stem cell harvest (SCH) and post-autologous stem cell transplant (PASCT) cellular composition data for 185 patients from the Myeloma XI trial. Utilising flow cytometry, SCH data was obtained from a 0.5ml aliquot of the total harvest and PASCT data was obtained from a peripheral blood sample collected 1-2 weeks post-transplant. Spearman's rank tests were performed across a variety of cell markers to assess for correlations between the cell count per µl and for correlations between the cell percentage (defined as the proportion of total CD45+ cells in each sample that expressed the given combination of cell markers) between the SCH and PASCT samples. Analysed cell marker phenotypes included CD45+, total CD3+, CD3/4+, CD3/8+, CD19+, and CD16/56+. Results We demonstrated statistically significant correlations for multiple cell markers between the composition of the SCH and peripheral blood 1-2 weeks post-transplant. Regarding cell count per µl, significant correlations were found in CD45+ (r=0.2168; p=0.0030), CD3+ (r=0.2254, p=0.0020), CD3/4+ (r=0.2050, p=0.0051), CD3/8+ (r=0.2733, p=0.0002), CD19+ (r=0.2787, p=0.0001), and CD16/56+ (r=0.3085, p<0.0001). Regarding cell percentages, significant correlations were found in CD3+ (r=0.3013, p<0.0001), CD3/4+ (r=0.3551, p<0.0001), CD3/8+ (r=0.4640, p <0.0001), CD19+ (r=0.2080, p=0.0048), and CD16/56+ (r=0.3221, p<0.0001). Further data assessing for correlations between harvest composition and progression-free and overall survival is also being analysed. Conclusions These data demonstrate clear correlations between higher lymphocyte counts in the stem cell harvest and higher lymphocyte counts 1-2 weeks post-autologous stem cell transplantation. Additionally, correlations between cell percentages indicate that harvest composition is directly correlated to the cellular composition of the blood following transplant. The correlations were statistically significant for a variety of phenotypes, including T cells, B cells, and NK cells, and indicate that the total dosage of lymphocytes re-introduced during transplantation may have wide ramifications for immune reconstitution as early as 1-2 weeks post-transplant. Our findings demonstrate that cellular composition of the harvest is a potentially important consideration that could influence immune reconstitution following autologous transplantation for myeloma. This research suggests that the lymphocyte constitution of the stem cell harvest, currently an overlooked metric during harvest collection, is correlated with immune recovery and further investigations may reveal implications for transplant outcome.