Long-Term Follow-up of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Patients After Stem Cell Mobilisation Under Imatinib.

Mobilisation and collection of in vivo-purged CD34+ stem cells for chronic myeloid leukemia (CML) patients while in complete cytogenetic remission (CCyR) may offer a therapeutic option for those who develop resistance to the tyrosine kinase inhibitor imatinib mesylate (IM), the recommended first line therapy. Indeed, several groups have reported on retrospective studies showing autologous stem cell mobilisation to be safe and efficacious during IM therapy. However, assessing the clinical utility of managing patients using this approach is difficult as long-term follow-up is lacking. Here, we report the clinical outcome for 22 CML patients with a median of 99.5 months follow-up post G-CSF induced stem cell mobilisation. We assessed the efficacy and the the impact on BCR-ABL1 expression levels in these individuals.

Stem cell mobilisation was achieved by administering 10 mg/kg body weight (bw)/day filgrastim (granulocyte-colony stimulating factor, G-CSF) subcutaneously. Stem cell apheresis was performed if the absolute number of circulating CD34+ cells exceeded 5/ml. Target stem cell yield was ³2×10⁶ CD34+ cells/kg body weight. BCR-ABL1 transcripts were quantified by real time PCR (Q-PCR) of reverse transcribed total RNA using LightCycler® with β-actin as endogenous control gene.

For the twenty-two patients included in the present study, median age was 47 years (range, 24 – 71) and median disease duration was 20 months (range, 1 – 77). At the start of IM, 19 patients were in chronic phase (CP), and 3 in accelerated phase (AP). With a median duration on IM of 16 months (range, 2 – 29), time to first CCyR was 6 months (range, 0 – 25) and time from CCyR to apheresis was 8.5 months (range, 1 – 20). Mobilisation was performed once in 16 patients and twice in 6 patients, of whom eighteen patients (82 %) proceeded to apheresis. Overall, mobilisation was successful in 17 of 22 patients (78 %) with a median CD34+ cell number of 3.1×10⁶/kg body weight (range, 0,7 - 6). BCR-ABL1 transcripts were undetectable in 12 of 22 peripheral blood samples (55 %) at the time of apheresis and 7 of 14 stem cell harvests (50 %) without discernible correlation with matched peripheral blood samples. Progression-free survival at 5 and 8 years was determined to be 63 %, and overall survival at 5 years and 8 years was 95 % and 90 %, respectively. Sixteen of 22 patients (73 %) continue to be treated with IM and twelve of 22 patients (55 %) are without detectable BCR-ABL1 transcripts, i.e. in complete molecular remission (CMR). Of the six patients that stopped IM (3 resistant and 3 intolerant), all received nilotinib as second-line TKI. Five of these six patients are still alive (1 in CHR; 1 in MCyR; 1 in MMR; and 2 in CMR), and one patient who subsequently received dasatinib died after progressing to blast crisis.

These observations show G-CSF induced stem cell mobilisation and collection during IM therapy for autologous transplantation to be safe and efficient with a favourable long-term outcome.

No relevant conflicts of interest to declare.