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.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT ABSTRACT:The effects of lifelong physical exercise on the composition, structure and mechanical properties of bone are not well understood. Earlier, we found that voluntary physical exercise improved various properties of bone in maturing male mice up to 6 months of age. In the present study, we extended the previous study to 18 months. Half of the mice (total N=144) had access to running wheels while half were kept sedentary. The collagen network was assessed biochemically and by tensile testing of decalcified bone. The mineralized femur was analyzed with pQCT and 3-point-bending of the diaphysis and neck-strength-test. The proximal tibia was analyzed with microCT. The bone collagen revealed inferior tensional properties with aging and the mineralized femur demonstrated decreased stiffness with age. In the running mice, tensile properties and the BMD were reduced at 18 months of age compared to the sedentary mice. In contrast, the stiffness of both the diaphysis and femoral neck was higher, and trabecular architecture and structure were improved in the running mice. In summary, the results suggest that lifelong exercise training of male mice results in more beneficial effects on intact mineralized bone in both the diaphysis and epiphysis than on bone collagenous matrix.

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Background Diffuse large B‐cell lymphoma (DLBCL) is a common indication for autologous stem cell transplantation (auto‐SCT). Study Design and Methods This prospective noninterventional study aimed to evaluate the impact of mobilization characteristics and graft cellular content on hematologic recovery and outcome after auto‐SCT among 68 patients with DLBCL. Results Better mobilization capacity as manifested by blood CD34+ cell count >32 × 106/L and CD34+ cell yield of the first apheresis >2.75 × 106/kg correlated with faster neutrophil (P = .005 and P = .017) and platelet (P = .002 and P < .001) recovery. A higher number of infused CD34+ cells (> 2.65 × 106/kg) was associated with better 5‐year overall survival (OS; 95% vs 67%, P = .012). The graft CD34+CD133+CD38− cell count >0.07 × 106/kg was predictive of better 5‐year OS (87% vs 63%; P = .008) and higher graft CD3+ cell count (>23.1 × 106/kg) correlated also with better 5‐year OS (80% vs 40%, P = .008). In multivariate analysis only disease status of CR I at auto‐SCT was associated with better progression‐free survival (P = .014) and OS (P = .039). Conclusion The mobilization capacity of CD34+ cells impacted on early hematologic recovery in patients with DLBCL after auto‐SCT. Higher graft CD34+ cell count and both CD34+CD133+CD38− and CD3+ cells were also associated with better OS. The effect of optimal graft cellular composition on outcome in DLBCL should be evaluated in a randomized study.