CY plus G-GSF yields more CD34+ cells but seems to diminish lymphocyte and NK cell counts in the grafts and hampers immune recovery after transplantation. Thus G-CSF alone might be a preferred mobilization method due to more rapid immune recovery posttransplant.
Background
Autologous stem cell transplantation (auto‐SCT) is a widely used treatment option in multiple myeloma (MM) patients. The optimal graft cellular composition is not known.
Study design and methods
Autograft cellular composition was analyzed after freezing by flow cytometry in 127 MM patients participating in a prospective multicenter study. The impact of graft cellular composition on hematologic recovery and outcome after auto‐SCT was evaluated.
Results
A higher graft CD34+ cell content predicted faster platelet recovery after auto‐SCT in both the short and long term. In patients with standard‐risk cytogenetics, a higher graft CD34+ count (>2.5 × 106/kg) was linked with shorter progression‐free survival (PFS; 28 vs. 46 months, p = 0.04), but there was no difference in overall survival (OS) (p = 0.53). In a multivariate model, a higher graft CD34+CD133+CD38− (>0.065 × 106/kg, p = 0.009) and NK cell count (>2.5 × 106/kg, p = 0.026), lenalidomide maintenance and standard‐risk cytogenetics predicted better PFS. In contrast, a higher CD34+ count (>2.5 × 106/kg, p = 0.015) predicted worse PFS. A very low CD3+ cell count (≤20 × 106/kg, p = 0.001) in the infused graft and high‐risk cytogenetics remained predictive of worse OS.
Conclusions
Autograft cellular composition may impact outcome in MM patients after auto‐SCT. More studies are needed to define optimal graft composition.
The available phase II and III data on plerixafor has been reviewed. The efficacy of plerixafor in the mobilization of CD34(+) cells in predicted poor mobilizers as well as in patients who had failed a mobilization has been evaluated. The pre-emptive use of plerixafor as well as studies on cost-effectiveness are covered. Also effects in the composition of the collected grafts along with the data on long-term outcome of plerixafor-mobilized patients is discussed. Expert commentary: Plerixafor combined with G-CSF mobilizes CD34(+) cells more efficiently than G-CSF alone in patients with NHL or MM. In phase III studies, engraftment after high-dose therapy has been comparable to G-CSF mobilized patients. The pre-emptive use of plerixafor added to mobilization with chemotherapy plus G-CSF or with G-CSF alone has gained more popularity. This approach may be more cost-effective than the routine use of this drug. The changes observed in the composition of grafts after plerixafor injection may have implications for post-transplant events.
The metabolic effects on rat cardiac and skeletal muscle of a strenous program of swimming, of cold acclimation and of isoprenaline treatment (0.3 mg/kg daily for 5 five-day weeks) were compared. Exercised and cold-exposed rats gained less body weight than did controls or isoprenaline-treated rats. In all treated groups the heart and the intercapular brown adipose tissue hypertrophied. The size of the adrenals increased only in isoprenaline-treated animals. Cold-acclimation and physical training increased and isoprenaline treatment reduced or did not affect the activities of succinate dehydrogenase, malate dehydrogenase and citrate synthase of cardiac muscle. In the skeletal muscle all treatments resulted in increased activities of these enzymes. Of the anaerobic enzymes analysed, only the activity of hexokinase increased in response to the treatements used. This increase was the same in cardiac as in skeletal muscle, but it was significantly greater with isoprenaline-treatment than with training or with cold-acclimation. The activities of lactate dehydrogenase and phosphofructokinase did not differ significantly. All treatments improved cold resistance, but only swimming exercise and cold acclimation significantly increased tolerance to exercise. It is concluded that prolonged stimulation of adrenergic beta-receptors by catecholamines is responsible for the metabolic changes observed.
In poorly mobilizing NHL patients, plerixafor added to chemomobilization is safe and effective. It also modifies the blood graft composition in many ways, some of which have been linked to better outcomes in previous studies. Larger sets of patients and longer follow-up are needed to see whether plerixafor-mobilized grafts are associated with superior outcome of the patients.
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