Relapse-free survival in multiple myeloma patients after autologous transplantation of peripheral blood stem cells depending of the content of CD45+CD19+ B cells in the apheresis product

Summary

Background

Currently 40% of autologous stem cell transplantation (auto-SCT) is performed for multiple myeloma (MM) patients, but so far there is no way the disease prognosis after auto-SCT having sufficiently high sensitivity and specificity. Objective To explore the relative content of CD45 + CD19 + B-lymphocytes in separated product from the MM patients and to investigate a possible relationship between the number of these cells and disease-free survival after autologous SCT.

Patients and Methods

The study included 17 patients with MM, who underwent high-dose chemotherapy with autologous SCT was performed over 2010-2012. The median age was 47 years (37-58 years). Mobilization of hematopoietic stem cells (HSC) was performed using high-dose cyclophosphamide (4 g/m2) followed by granulocyte colony-stimulating factor 5-10 mg/kg/day. Apheresis procedure was performed using a blood cell separator AS TEC 204 (Fresenius) and Spectra LRS 07 (COBE). At the time of auto-SCT, 6 patients were in complete remission, 9, in partial response and 2 had a resistant disease. Conditioning regimen included melphalan 140-200 mg/m2. 5.6±0.6×106 CD34+ HSC/kg (2.6-13.9×106 CCM/kg) were transplanted. CD45 + CD19 + B cell counts of in separation product were assessed by flow cytometry (BD FACSCalibur). The data are presented as Me (min-max) or M ± SE. Statistical analysis was performed using Statistica 6.0 (StatSoft). To assess significance of differences in continuous variables between independent groups of patients, we used a non-parametric U-Mann-Whitney (PU) test. To evaluate diagnostic values, we used ROC-analysis with calculation area under the curve (AUC). Survival analysis was carried out using the Kaplan-Meier method to estimate the reliability of log-ranktest.

Results

Median observation period after auto-SCT was 44.1 months (4-67.2 months). Median survival was 38.3 months. There were no significant differences between the patients in remission (n=8) and relapse (n=9), in age (48 vs. 46.5 years; Pu = 0.74), re-infused HSC number (4.8± 0.5 versus 6.5 ± 1.1×106/kg P=0.23), and disease status at the time of auto-SCT. Higher levels of CD45+CD19+ B cells in apheresis product were founded in MM patients with relapse (5.7 ± 0.9 vs 2.9 ± 0.9% in remission patients; P=0.046). By means of ROC analysis we have found AUC= 0.80 (95% CI: 0.588- 1.012; p = 0.040). The method showed 100% sensitivity and 60% specificity, with a likelihood ratio of 2.5 at the cut-off point of 2.5% for CD45 + CD19 + B cells. We have revealed significant differences (P log-rank=0.028) when analysing disease-free survival of MM patients after autologous SCT by Kaplan-Meier method, depending on the relative content of CD45 + CD19 + B cells in apheresis product.

Conclusion

In patients with MM, relative content of >2.5% CD45 + CD19 + B-cells in product apheresis may be considered an adverse prognostic factor indicating shorter period of disease-free survival (-16.8 months). Relative content of < 2.5% CD45+ CD19 + B-cells in apheresis product may be associated with prolonged disease-free survival period.

Keywords

Multiple myeloma, autologous hematopoietic stem cell transplantation, cd19+ b-cells, apheresis product