Viability and Quantification of Progenitor Cells in Venesected Blood from Patients Receiving Escalated-Dose Epirubicin and Cyclophosphamide with G-CSF for Lymphoma: Potential Role in Further Increasing Dose-Intensity

Abstract

We assessed the concentration of haemopoietic progenitors in peripheral blood in six patients with de novo intermediate grade non-Hodgkin's lymphoma receiving multiple cycles of escalated dose epirubicin and cyclophosphamide on day 1 followed by 5ug/kg of G-CSF (filgrastim) on days 2-14. Specimens were taken at days 12, 15 and 18 in cycles 1 and 2 and on day 15 for cycles 3-6. Progenitor numbers were maximal on day 15 in cycles 1 and 2. The median number of granulocyte-macrophage colony forming cells (GM-CFC) and CD34⁺ cells on day 15 of cycles 1 and 2 was 3.8 × 10⁴/ml and 11 × 10⁴/ml, respectively. A 600ml venesection at this time would contain a median of 36 × 10⁴ GM-CFC/kg (range 25-47) and 1.04 × 10⁶ CD34⁺ cells/kg (range 0.73-1.4), based on individual patient weights. Day 15 progenitor numbers were maintained for the first 3 cycles but tended to fall thereafter. The viability of the progenitors collected in whole blood and stored at 4×C for various time intervals was also assessed. The median percent of GM-CFC and erythroid blast forming units (BFU-e) surviving after storage for 48hrs was 79% and 69% respectively and after 72hrs was 48% and 63% respectively. Serum collected 2hrs after the completion of chemotherapy had minimal inhibitory effect on progenitors collected prior to treatment.

Our data demonstrate that two weeks after anthracycline-based chemotherapy and G-CSF in previously untreated patients the peripheral blood contains large numbers of progenitors. A 600ml venesection at this time stored at 4×C, and then reinfused after the next cycle of chemotherapy would contain sufficient viable progenitors to potentially hasten haematological recovery.

Key Words:

• G-CSF
• progenitors
• NHL
• high-dose chemotherapy