Stem cell collection and hematological recovery in the Fondazione Italiana Linfomi (FIL) MCL0208 clinical trial

Abstract

In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 10⁶ PBSC/kg, 2.6% (n = 7) mobilized < 4 × 10⁶ PBSC/kg and 7.7% (n = 21) failed the collection. Similar results were obtained for the planned second leukapheresis, with only one patient failing both attempts. Median count of reinfused PBSC was 5 × 10⁶/kg and median time to recovery from neutropenia G4 was 10 days from ASCT. No impact of mobilizing subtype or number of reinfused PBSC on hematological recovery and LEN dose reduction was noted. At a median follow-up of 75 months from ASCT, PFS and OS of transplanted patients were 50% and 73%, respectively. A long lasting G4 neutropenia after ASCT (> 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes.

Keywords: Autologous stem cell transplantation (ASCT); Hematological recovery; Leukapheresis (LK); Mantle cell lymphoma (MCL); Peripheral blood stem cells (PBSC).

Figure 1

Study flow chart. Consort of the study protocol with focus on harvest results and reasons of interruption. Patients undergoing leukapheresis after the 2 courses of HD-ARA-C and MRD results are depicted on the top-right of the diagram. pts patients; Ara-C cytarabine; HRVST harvest; INSUFF insufficient; SUFF sufficient; MRD minimal residual disease; BEAM carmustine with etoposide, cytarabine and melphalan; ASCT autologous stem cell transplantation; PD progressive disease; AE adverse event; R randomisation; Lena lenalidomide.

Figure 2

Kaplan Meier estimates of PFS (A) and OS (B) of transplanted patients.

Figure 3

Kaplan–Meier estimates of PFS (A) and OS (B) of all transplanted patients according to days of recovery from neutropenia G4 (up to 10 vs 11 and more) after ASCT. G4 grade 4; ASCT autologous stem cell transplantation.

Figure 4

Kaplan–Meier estimates of PFS of transplanted patients according to MRD by RQ-PCR on leukapheresis samples. MRD minimal residual disease; RQ-PCR quantitative real-time polymerase chain reaction.