ISSN 1866-8836
Клеточная терапия и трансплантация

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

Irina V. Kruchkova, Svetlana A. Sizikova, Galina U. Ushakova, Vera V. Sergeevicheva, Darya S. Batorova, Egor V. Batorov, Natalya V. Pronkina, Andrey V. Gilevich, Elena R. Chernykh
Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia

Contact: Dr. Irina V. Kruchkova
E-mail: bmt-novosibirsk@mail.ru
doi 10.18620/ctt-1866-8836-2016-5-3-44-46
Submitted 23 August 2016
Accepted 20 September 2016

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Cellular Therapy and Transplantation (CTT)
Volume 5, Number 3
Contents 

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


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