Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment

Abstract

Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m(2) and granulocyte colony-stimulating factor (G-CSF) 10 microg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was >or=2.0x10(6) CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3x10(6) CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.

Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment

“…Autoimmune hemolytic anemia has been reported. Long-term hematopoietic stem cell damage may also persist, as evidenced by the occasional difficulty in Abbott 25 www.TheOncologist.com mobilization of autologous stem cells in some prior recipients of nucleoside analogues [42,43]. Finally, there are rare reports of secondary acute myeloid leukemia following nucleoside analogue treatment [44].…”

Blood stem cell mobilization and collection in patients with chronic lymphocytic leukaemia: a nationwide analysis

“…As suggested by earlier studies, longer time from the last chemotherapy to mobilization may be associated with better mobilization outcome. 20,21 The time interval from previous chemotherapy to mobilization was at least 2 months in 74% of the patients in our analysis, but a longer waiting time might have improved collection success in at least some patients.…”

“…This is in line with previous findings. 21 However, the platelet count was 4100 Â 10 9 /l in 70% of the patients who failed in the initial collection, making this factor of limited practical value. On the other hand, if a platelet count is o100 Â 10 9 /l at the start of mobilization therapy, the chances of successful mobilization are minimal.…”

“…Based on this survey as well as previous studies 8,11,12,14,15,[20][21][22] (Table 4), patients with CLL are more difficult to mobilize than many other haematological patient groups. Previous treatments have been variable, as have the mobilization regimens used preventing more detailed conclusions, but success rates for collections have been in the order of 60-70% in most studies.…”

How we mobilize haemopoietic stem cells

“…A failure rate of up to 59% for collection was described in chronic lymphocytic leukaemia patients following fludarabine use, particularly with more prior fludarabine cycles, <2 months since fludarabine exposure and prior fludarabine-cyclophosphamide combination therapy. 20 Biological agents, such as the immunomodulatory agents, may also impair stem cell mobilization although, at least with lenalidomide, this block may be overcome with the use of chemotherapy-or plerixafor-containing mobilizing regimens. 21,22 Identifying suboptimal mobilizers during G-CSF treatment…”