Delta-Neutrophil Index Is a Useful Indicator for Initiation of Peripheral Blood Stem Cell Collection in Chemo-Mobilized Patients

Introduction: The most powerful predictor of successful peripheral blood stem cell (PBSC) collection is the count of circulating CD34+ cell on the starting day of harvest. However, measurement of CD34+ cell requires flow-cytometry method and the decision of PBSC collection initiation usually does not depend on CD34+ count result in real practice. Delta-neutrophil index (DNI) is a calculated parameter from an automated blood cell analyzer (ADVIA 120, Siemens, Inc.) which shows the difference in leukocyte subfractions by cytochemical myeloperoxidase reaction and nuclear lobularity assay. We investigated on DNI as a potential indicator for initiation of autologous PBSC harvest.

Materials and Methods: Total 114 patients who received chemo-mobilization in Severance Hospital from October 2010 to March 2014 were enrolled. All data were collected retrospectively from the patients’ medical records. Mobilization chemotherapy regimens were selected by the physician.G-CSF (600mcg/day) was administered from 1 to 3 days after end of chemotherapy until the last day of PBSC collection. Peripheral blood complete blood cell count and DNI was done daily from the end of chemotherapy. Measurement of CD34+cell was done only on the first day of harvest. Collection was initiated when the white blood cell (WBC) count rebounded > 3.0 x 10⁹/L. We evaluated correlation of collected CD34+ cell count (/Kg) and DNI and tried to find the cutoff value of DNI for successful harvest.

Results: PBSC collection data of total 114 patients were retrospectively reviewed (lymphoma n=96; multiple myeloma n=18). Mobilization regimen were variable (high dose etoposide n=71; high dose cyclophosphamide n=17; DHAP n=11; IVAM n=9; ICE n=2; high dose MTX+Ara-C n=3; other n=2). Median cycle number of previous chemotherapy line was 1 (range 1-5), and chemotherapy number 6 (1-18). 17 patients (14.9%) received radiation therapy. The median number of G-CSF was administered median 10 days (range 4-22). Peripheral blood CD34+ cell counting was done in 58 patients (50.9%). For 58 patients, WBC count, neutrophil count, mococyte count, DNI showed correlation with CD34+ cell (/mcL). Also interval between the day before harvest of WBC, neutrophil, monocyte showed correlation with CD34+ cell(/mcL). The highest correlation coefficient was shown with PB CD34+ count (ρ=0.876, P<0.001) followed by DNI (ρ=0.470, P<0.001), WBC interval (ρ=0.414, P<0.001), neutrophil interval (ρ=0.348, P<0.001), first day WBC (ρ=0.324, P<0.001). When successful first day apheresis was defined as > 1.0 x 10⁶/kg, receiver operator characteristic (ROC) curve analysis showed DNI cutoff of 11.75 which had area under the curve (AUC) of 0.875 (sensitivity 81%, specifity 85.7%, P< 0.001). And if successful first day apheresis was defined as > 2.0 x 10⁶/kg, receiver operator characteristic (ROC) curve analysis showed DNI cutoff of 13.75 which had area under the curve (AUC) of 0.845 (sensitivity 82.1%, specifity 76.7%, P< 0.001).

Summary and Conclusion: DNI correlates with peripheral circulating CD34+ count on the first day of PBSC harvest after chemo-mobilization. And it has very high sensitivity and specifity for prediction of successful collection on first day. DNI may be used as useful marker for initiation and prediction of successful PBSC collection in chemo-mobilized patients.