Identification of Factors Associated with Poor Hematopoetic Cell Mobilization and Collection from Peripheral Blood in Non-Hodgkin’s Lymphoma; Single Center Analysis of 80 Patients.

To identify the factors influencing hematopoetic cell collection we performed an analysis of a group of patients with uniform diagnosis treated in single center.

Patients and methods: For this study we selected out of 1205 transplantation procedures performed in our department a group of 80 patients with non-Hodgkin’s lymphoma (NHL): M/F 42/38, median age 38,5, 17–66 y, who underwent peripheral blood progenitor cell (PBPC) harvest and autologous hematopoetic cell transplantation. The histological NHL subtypes were as follows: -follicular (n=13), -mantle cell (n=2), -small lymphocytic (n=9), -diffuse large B-cell (n=23), -lymphoblastic (n=11), -anaplastic (n=11) and other subtypes (n=11). The involvement of bone marrow at diagnosis or in relapse was proved in 27 patients. Most patients were heavily pretreated: the median time from diagnosis to mobilization was 12,5 months (3,7–70,8). The median number of different chemotherapy regimens was 2 (1–7) and the med. no. of chemotherapy cycles equaled to 9 (3–30). 34 patients received in addition radiation therapy. At the time of PBPC mobilization, 30 patients were in 1^st remission (CR), 7 were in ≥2^nd CR; 41 patients were in PR and 2 in relapse.

Mobilization and harvesting procedures. In 27 patients pre-mobilization chemotherapy consisted of a single high dose of cyclophosphamide - 4,g/m², 40 patients received IVE (Ifosfamide 3g/m²/d 1–3, Etoposide 0,2g/m²/d 1–3, epirubicine 0,05g/m²/d 1) and 10 patients were given other regimens: Cladribine, COP, F-MACHOP, Mtx, DHAP. Five days after the last chemotherapy dose G-CSF was started at 10mg/kg/day sc and continued until the last day of collection. Apheresis was performed using CS 3000 cell separators.

The goal of this study was to determine factor associated with poor number of collected CD34+ cells. The following end-points were taken into account: <1.0x10⁶ CD34+ cells/kg collected on the first day of harvest, <1.0x10⁶ CD34+ cells/kg after two days of harvest, <1.0, <2.5, <5.0x10⁶ CD34+ cells/kg after one entire harvesting procedure. Following variables were analyzed for their impact on the harvest efficacy: sex, age, histological subtype, bone marrow involvement, number of different chemotherapy regimens, number of chemotherapy cycles, adjuvant radiation therapy, chemotherapy scoring system (Drake M), scoring system of myelotoxic chemotherapy (Vantelon JM), time from diagnosis to mobilization, disease status at mobilization and mobilization regimen.

Results: Univariate analysis selected the factors associated with unsuccessful harvest (p<0.05) as follows: bone marrow involvement at any time prior to mobilization, diagnosis of low grade lymphoma, a high number of chemotherapy regimens and cycles, additional radiation therapy, type of mobilization regimen (others vs IVE). The subsequent multivariate analysis identified following adverse risk factors: low grade NHL (p 0.01–0.004), bone marrow involvement at any time of treatment (p=0.01–0.002), B line NHL (p=0.04–0.009), number of therapy regimens >2 (p=0.03–0.0001), radiation therapy (p=0.01–0.02), scoroing system of myelotoxic chemotherapy (p=0.02–0.03), mobilization other then IVE (p=0.02–0.0007). Like in our earlier study IVE was found the most effective pre-mobilization regimen

Conclusions: The factors associated with poor mobilization of peripheral blood progenitors in this study were: low grade lymphoma, bone marrow involvement, heavy pretreatment and mobilization regimen other then IVE.