Impaired Mobilization of Peripheral Blood Stem Cell (PBSC) after Fludarabine Treatment: Comparison of Results Using 3 Different Procedures.
Authors: Genet Philippe , Travade Philippe , Cazin Bruno , Lepretre Stephane , Divine Marine , Martin Claude , Leblond Veronique , Van Den Neste Eric , Maloisel Frederic , Michallet Mauricette , Eghbali Houchingue , Berthou Christian , Delmer Alain , Grosbois Bernard , Feugier Pierre , Leporrier Michel , Sutton Laurent , Tournilhac Olivier 
Published: October 2019

Preliminary studies have shown that autologous PBSC transplantation could be an interesting approach for patients with advanced CLL. As the duration of response after transplantation appears to be correlated to the response at time of transplantation, optimal treatment should precede the transplantation procedure. Fludarabine (FDR), alone or associated with cyclophosphamide (CPM), seems to be appropriate. However, it has been previously suspected that FDR impairs subsequent PBSC collection in CLL patients. Factors influencing these results are poorly understood. To better assess the influence of both treatment and mobilization procedure on PBSC mobilization, we analysed the results of 2 prospective trials of the French Cooperative Study Group on CLL.

The first trial (trial 1) involved 38 Binet stage B or C patients in CR or in PR after front-line therapy with 6 monthly cycles of FDR (30 mg/m2/d) + CPM (200 mg/m2/d) for 5 consecutive days (B. Cazin, Blood 2002, 100, 773a). At least 2 months after the last course of chemotherapy, a single mobilization with G-CSF alone was done. Filgrastim (10 μg/kg per day) or lenograstim (7 μg/kg per day) were used. The collected PBSC were frozen and could be used for autologous stem cell transplantation (ASCT) at relapse (O. Tournilhac, Blood 2004, 103, 363–365).

The second study (trial 2) is an ongoing prospective trial evaluating the efficiency of front-line ASCT in stage B and C patients. All patients were initially treated with 3 mini-CHOP followed by 3 courses of FDR. Patients in CR underwent PBSC mobilization with G-CSF alone (lenograstim 10 μg/kg per day), at least 8 weeks after the last course of FDR and were subsequently randomized between observation and high dose CPM+TBI followed by ASCT. Patients not in CR received 1 or 2 DHAP with G-CSF (lenograstim 150 μg/m2 per day) for PBSC mobilization and were randomized to receive either ASCT with the same regimen as above or 3 courses of FDR+CPM.

In the 2 trials, the goal of the mobilization was to obtain more than 2 x 106 CD34/kg. We focused the analysis on the result of the first mobilization procedure of every patient to allow the comparison between the 2 trials. Results of PBSC collection are summarized below:

These results show that mobilization with G-CSF alone provides poor results in CLL patients treated with FDR as front-line therapy, whatever the modalities of FDR treatment. On the other hand, the impact of fludarabine can be overcome by using DHAP for PBSC mobilization, allowing its use before PBSC mobilization and ASCT in CLL patients.

(1) t-test: G-CSF vs G-CSF+DHAP (p<0.001) Previous chemotherapy FDR+CPM (trial 1) Mini-CHOP+FDR (trial 2) Mini-CHOP+FDR (trial 2) Mobilization procedure G-CSF G-CSF G-CSF+DHAP n 38 37 47 %CD34>2x106kg (1) 15.8% 29.7% 78.7% Median CD34 (x106/kg) 1.48 (0.47–3.45) 1.65 (0.38–6.49) 5.07 (0.34–53,07)