ABSTRACT
Collection of peripheral blood stem cells (PBSCs) for autologous stem cell transplant (ASCT) requires mobilization from the bone marrow. There is variation in mobilization choice;during the COVID-19 pandemic BSBMT&CT guidelines recommended using granulocyte-colony stimulating factor (G-CSF) alone to minimize the use of chemotherapy. We report on the impact of mobilization regimen on stem cell collection, and whether IMiD-containing induction therapy impacts on mobilization and consequently transplant engraftment times for 83 patients undergoing ASCT at Leeds Teaching Hospitals. Cyclophosphamide plus G-CSF (cyclo-G) mobilization yielded more CD34+ cells (8.94 vs. 4.88 x106/kg, p = < 0.0001) over fewer days (1.6 vs. 2.4 days, p = 0.007), and required fewer doses of salvage Plerixafor than G-CSF only (13.6% vs. 35%, p = 0.0407). IMiD-containing induction impaired all of these factors. CD34+ doses > 8x106/kg were more frequent with Cyclo-G (62% vs. 11%, p = 0.0001), including for those receiving IMiD 1st line induction (50% vs. 13.3%, p = 0.0381). Note that 92.6% of those receiving IMiD-free inductions were mobilized with Cyclo-G. The novel agents used in modern induction regimens (e.g Daratumumab) have been shown to impair yields, increasing the importance of optimizing mobilization regimens in the first instance. Furthermore, as cellular therapies become established in the management of multiple myeloma emerging data highlights the potential benefits of stem cell top up in the management of the haematological toxicities of these therapies. Our findings support re-adoption of Cyclo-G as the gold standard for mobilization to optimize PBSC harvesting and ensure sufficient cells for subsequent ASCTs.Copyright © 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.
ABSTRACT
Collection of peripheral blood haematopoietic stem cells (PBSC) for autologous stem cell transplant (ASCT) requires mobilisation with granulocyte colony-stimulating factor either alone (GCSF) or in combination with chemotherapy, typically cyclophosphamide (Cyclo-G). There is variation between UK centres in mobilisation choice;during the Covid-19 pandemic BSBMT&CT guidelines recommend GCSF alone. Front-line myeloma induction regimens also vary across the UK;some centres favour IMiD-containing induction (VTd) and others cyclophosphamide-containing (VCd). This retrospective study evaluates the mobilisation strategies within a regional comprehensive cancer centre after IMiD-based and IMiDfree induction. Eighty-three patients underwent 86 mobilisation procedures between Jan 2016 and Sept 2021. Sixty-six harvests used Cyclo-G (Cyclophosphamide 2 g/m2 then GCSF 5 mcg/kg for 10 days), and 20 used GCSF (10 mcg/kg for 5 days). CD34+ minimum target was >4 × 106 /kg with an optimal target of >8 × 106 /kg, corresponding to safe and optimal doses, respectively, for two ASCTs. Outcomes included CD34+ yield, days of harvesting, rescue plerixafor use and complications. Groups were compared using the Mann-Whitney or Chisquared tests. 86.04% of harvests collected the minimum target (failure rates: Cyclo-G 10.6% vs. 25% for GCSF p = 0.1). Cyclo-G yielded higher CD34+ doses (8.94 vs. 4.88 × 106 /kg, p = <0.0001) and required fewer apheresis days (1.6 vs. 2.4 days, p = 0.007). Optimal harvest yield was more frequent with Cyclo-G (62% vs. 11%, p = 0.0001), including for those receiving IMiD 1st line induction (50% vs. 13.3%, p = 0.0381). CD34+ yields were lower after IMiD-containing (thalidomide or lenalidomide) induction (5.18 vs. 8.98 × 106 /kg, p = 0.00003, n = 32) though there was a trend towards higher yields when Cyclo-G was used (5.8 vs. 4.8 × 106 /kg, p = 0.34). In patients mobilising after 1st line IMiD therapy ( n = 27), Cyclo-G did result in higher yields (8.51 vs. 5.18 × 106 / kg, p = 0.0321). The improved mobilisation of PBSCs with Cyclo-G is reflected in increased preapheresis day 1 CD34+ counts (95 vs. 46.94 × 106 /kg, p = 0.06). More patients mobilised with GCSF required plerixafor (35% vs. 13.6%, p = 0.0407). Five patients receiving Cyclo-G were hospitalised, including one with neutropenic sepsis. There were no infective complications from mobilisation with GCSF. In summary, Cyclo-G mobilisation yielded more cells over fewer days, and required fewer doses of salvage plerixafor than GCSF-only. IMiD-based induction impaired all of these factors. Of note, 92.6% of those receiving IMiD-free inductions were mobilised with Cyclo-G, meaning differences may be attributable not only to mobilisation regimen but also in part to induction therapy. In the UK, where VTd versus VCd use varies, our study suggests mobilisation with Cyclo-G should be considered preferable in patients having VTd induction. Cyclo-G additionally saves costs by reducing plerixafor use and apheresis unit days. Commissioning arrangements for plerixafor mean access to this medication is not unlimited, which underlines the importance of achieving optimal CD34+ mobilisation without its use. Future myeloma therapies will incorporate more novel agents into induction regimens (e.g. daratumumab), which further compromises PBSC harvesting. Thought should be given to re-adoption of Cyclo-G as the gold standard for mobilisation to optimise PBSC harvesting and ensure sufficient cells for subsequent ASCTs. (Table Presented).