Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study

In our single-center study, 357 myeloma and lymphoma patients between 2009 and 2019 were mobilized with granulocyte colony-stimulating factor (G-CSF 7.5 µg/kg bid for four days) plus a fixed dose of 24 mg Plerixafor when indicated (Plerixafor Group, n = 187) or G-CSF alone (G-CSF Group, n = 170). The target CD34 cell yields were ≥2.0 × 106 CD34+ cells/kg in lymphoma and ≥4.0 × 106 CD34+ cells/kg in myeloma patients to enable putative second transplants in the latter. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the control group in the myeloma cohort, with lymphoma patients not requiring Plerixafor showing significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions, probably due to the significantly lower number of CD34-positive cells re-transfused. While in myeloma patients the outcome (overall survival, progression-free survival) following autologous stem cell transplantation (ASCT) was similar between the Plerixafor Group and the control group, hard to mobilize lymphoma patients had significantly poorer progression-free survival (47% vs. 74% at 36 months after ASCT, p = 0.003) with a trend also to poorer overall survival (71% vs. 84%). In conclusion, while there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT. Whether disease characteristics and/or a more intense or stem cell-toxic pre-mobilization chemo-/radiotherapy burden in this cohort are responsible for this observation remains to be shown in future studies

Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study

In our single-center study, 357 myeloma and lymphoma patients between 2009 and 2019 were mobilized with granulocyte colony-stimulating factor (G-CSF 7.5 µg/kg bid for four days) plus a fixed dose of 24 mg Plerixafor when indicated (Plerixafor Group, n = 187) or G-CSF alone (G-CSF Group, n = 170). The target CD34 cell yields were ≥2.0 × 106 CD34+ cells/kg in lymphoma and ≥4.0 × 106 CD34+ cells/kg in myeloma patients to enable putative second transplants in the latter. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the control group in the myeloma cohort, with lymphoma patients not requiring Plerixafor showing significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions, probably due to the significantly lower number of CD34-positive cells re-transfused. While in myeloma patients the outcome (overall survival, progression-free survival) following autologous stem cell transplantation (ASCT) was similar between the Plerixafor Group and the control group, hard to mobilize lymphoma patients had significantly poorer progression-free survival (47% vs. 74% at 36 months after ASCT, p = 0.003) with a trend also to poorer overall survival (71% vs. 84%). In conclusion, while there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT. Whether disease characteristics and/or a more intense or stem cell-toxic pre-mobilization chemo-/radiotherapy burden in this cohort are responsible for this observation remains to be shown in future studies

The iron-responsive element (IRE)/iron-regulatory protein 1 (IRP1)–cytosolic aconitase iron-regulatory switch does not operate in plants

Animal cytosolic ACO (aconitase) and bacteria ACO are able to switch to RNA-binding proteins [IRPs (iron-regulatory proteins)], thereby playing a key role in the regulation of iron homoeostasis. In the model plant Arabidopsis thaliana, we have identified three IRP1 homologues, named ACO1–3. To determine whether or not they may encode functional IRP proteins and regulate iron homoeostasis in plants, we have isolated loss-of-function mutants in the three genes. The aco1-1 and aco3-1 mutants show a clear decrease in cytosolic ACO activity. However, none of the mutants is affected in respect of the accumulation of the ferritin transcript or protein in response to iron excess. cis-acting elements potentially able to bind to the IRP have been searched for in silico in the Arabidopsis genome. They appear to be very rare sequences, found in the 5′-UTR (5′-untranslated region) or 3′-UTR of a few genes unrelated to iron metabolism. They are therefore unlikely to play a functional role in the regulation of iron homoeostasis. Taken together, our results demonstrate that, in plants, the cytosolic ACO is not converted into an IRP and does not regulate iron homoeostasis. In contrast with animals, the RNA binding activity of plant ACO, if any, would be more likely to be attributable to a structural element, rather than to a canonical sequence