Evaluation of Progenitor Cells (CFU-GM, CFU-GEMM, BFU-E, CD34+ Cells) and White Blood Cells in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with Rituximab-CHOP-14 and Supported with Pegfilgrastim.

Purpose: To investigate the behavior of CFU-GM, CFU-GEMM, BFU-E, CD34+ cells and white blood cells before and during six courses of dose-dense immune-chemotherapy (R-CHOP-14) supported by pegfilgrastim in eight patients affected with newly diagnosed diffuse large B cell lymphoma (3 men, 5 women, aged 18–51).

Patients and Methods: The standard-dose CHOP chemotherapy was delivered every 14 days, preceded on day 1 by rituximab (375 mg/m²) and followed on day 3 by pegfilgrastim (6 mg per cycle). In each course of therapy, the evaluation was performed before treatment (day 1) and on days +3, +6, +8, +10 and +13. Hemopoietic progenitors were assayed in a complete StemCell medium (MethoCult^TM GF H4434 StemCell, Canada) and counted with an inverted microscope after 14-day incubation at 37°C, in 5% CO₂. CD34+ cells were evaluated with flow cytometry (EPICS XL, Beckman Coulter); WBC were evaluated with an automatic counter (ADVIA 120 Bayer).

Results: The peak of CFU-GM, CFU-GEMM, BFU-E colonies and of CD34+ cells was invariably reached on day +13 and the highest absolute values were detected after the first cycle of therapy: CFU-GM/ml 3704±738; CFU-GEMM/ml 199±62; BFU-E/ml 8848±3499; CD34+cells/μL 33±3. In the subsequent courses, the number of both hematopoietic colonies and of CD34+ cells progressively lowered; however, the median value of CD34+ cells was still over 20/μL (range 20–35/μL) before the start of the fourth cycle of R-CHOP-14. A significant direct correlation was found between the number of CFU-GM, CFU-GEMM and BFU-E colonies and that of CD34+ cells (p<0.05). The WBC peak was constantly reached on day +6, with a mean value, all cycles considered, of 32±14 x 10⁹/l.

Comments: Hemopoietic progenitor cells kynetic showed that colonies and CD34+ cells started to increase at the WBC nadir. Most important, the level of circulating CD34+ cells at day 13 of the first three cycles of therapy was above 20/μL which we consider permissive for a productive leukaferesis; this observation adds further evidence of the pegfilgrastim progenitor cells mobilizing capacity.