A Retrospective Comparison between Cyclophosphamide (Cy) Followed by G-CSF, and Ifosfamide, Etoposide and Epirubicin (IVE) Plus G-CSF Mobilisation Regimes in Haematological Malignancies.
Authors: Ortin Miguel , Bricknell Sue , Gribben Sheila , Stirrup Lynn , Dyer Martin , Hunter Ann 
Published: April 2020

Background: High dose intensity protocols supported by autologous peripheral blood progenitor cell (PBPC) infusions are an intrinsic part of therapy in a number of haematological malignancies. Success rates depend on the ability to collect adequate numbers of PBPC. Several mobilization regimens have been designed, with Cy/G-CSF being the most widely used. In the present study, we retrospectively compared the PBPC yields of harvests after IVE with those of standard Cy/G-CSF priming. Patients and Methods: Between January-2004 and June-2005, 49 patients with haematological malignancies [multiple myeloma (MM), 29 cases; non-Hodgkin lymphoma (NHL), 16; Hodgkin’s Disease (HD), 4] were harvested after priming with either IVE or Cy/G-CSF. IVE consists on ifosfamide 3 g/m2 plus etoposide 200 mg/m2 on days 1 to 3, plus epirubicin 50 mg/m2 on day 1, followed by G-CSF 300 microg/day from day 8. Cyclophosphamide priming consists on Cy 3 g/m2 on day 1, followed by G-CSF 300 microg/day from day 5. The target PBPC yield was 2.5 x106 CD34+ cells/Kg, and patients had daily collections until the required number of cells was reached (1–3 leucopheresis). Endpoints included CD34+ and CFU-GM yields (overall and per pheresis), and number of pheresis required.

Results: Fifty procedures were performed in 49 patients; 35 using Cy/G-CSG (5 NHL, 29 MM, 1 HD) and 15 using IVE (11 NHL, 1 MM, 3 HD). One patient with MM underwent 2 procedures. All patients receiving IVE achieved the required cell dose in a maximum of 2 pheresis (40% in one, 60% in two).Of the patients receiving Cy, only 80% achieved the required cell dose, with 20% needing one, 60% two and 20% three pheresis (p&lt;0.001). CD34+ counts were significantly higher in cases primed with IVE, both from individual pheresis and in total final counts. CFU-GM yields, however, appeared to follow different dynamics: As shown in Table 1, both the final and the first pheresis yields are significantly superior in cases mobilized after IVE, whilst no difference was found in the second day of harvest. IVE priming appeared to yield significantly higher CD34+ counts in NHL (p&lt;0.04). No differences in toxicity between Cy and IVE were seen.

Conclusion: Priming with IVE yields higher PBPC numbers than cyclophosphamide, patients requiring fewer pheresis, therefore reducing the cost. NHL patients appear to be the most benefited. The differences observed in the dynamics followed by the mobilization of CD34+ cells and CFU-GM suggest IVE and Cy act in different ways and on different cell populations.

Table 1: CFU-GM (x 10^4/Kg) and CD34+ (x 10^6/Kg) total and per session Session (cell type) 1st (CD34+) 2nd (CD34+) Total (CD34+) 1st (CFU–GM) 2nd (CFU–GM) Total (CFU–GM) Cy 2.5±2.8 1.9±1.6 4.3±3.5 18.3±16.4 19.6±16.1 35.6±26.3 IVE 6.2±6.7 4.3±4.2 8.8±6.4 48.8±55.6 24.1±11.4 60.0±48.1 p value &lt;0.001 &lt;0.007 &lt;0.001 &lt;0.001 &lt;0.3 &lt;0.02