Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard of care for transplant-eligible patients with multiple myeloma (MM). Among factors that influence outcome after autoHSCT, it has been suggested that the number of natural killer (NK) cells plays an important role. However, the impact that different NK cell subsets and their phenotype could have in disease progression after autoHSCT are less clear. For this reason, we have phenotypically and functionally characterized NK cells during immune system reconstitution after autoHSCT in 54 MM patients. Shortly after leukocyte recovery, an extensive redistribution of NK cell subsets occurs in these patients. In addition, NK cells undergo a profound phenotypic change characterized, among others, by their increased proliferative capacity and immature phenotype. Importantly, MM patients who showed lower frequencies of the mature highly differentiated NKG2A-CD57+ NK cell subset at +30 and +100 days after autoHSCT experienced superior progression-free survival and had a longer time to the next treatment than those with higher frequencies. Our results provide significant insights into NK cell reconstitution after autoHSCT and suggest that the degree of NK cell maturation after autoHSCT affects the clinical outcome of MM patients treated with this therapeutic strategy.
We have recently reported (Alonso-deFlorida, del Castillo, Gonzalez & Sanchez, 1965) that chronically denervated diaphragmatic muscle of the guinea-pig not only becomes supersensitive to acetylcholine but also exhibits a considerable and unexpected sensitivity to histamine and bradykinin. Moreover, strips of denervated diaphragm taken from sensitized guinea-pigs contract in the presence of small concentrations of the homologous antigen, a finding which largely confirms the experiments of Ado & Ginetsinskii (1944) and Ado, Ginetsinskii & Shamarina (1946) on the allergic reaction of denervated muscles of the dog in situ.These results are interesting for two main reasons. First, they show that denervated guinea-pig diaphragm develops chemical receptors to compounds which are inactive before the degeneration of the phrenic nerve; this finding offers a fresh opportunity to probe into the mechanisms by which the motor nerve controls the chemical sensitivity of the muscle membrane. Second, the fact that skeletal muscle can show anaphylactic responses is important technically, since striated muscle fibres are larger than smooth muscle cells and more suitable for the study of the changes in membrane permeability and electrical properties elicited by the antigen on sensitized tissues. This paper describes the responses of denervated muscle strips to histamine and antigenic proteins. The effect of histamine is compared with that of acetylcholine; our investigation of the effects of the homologous antigen follows the lines of the classical work of Schultz (1910) and Dale (1913) on the in vitro anaphylactic responses of visceral smooth muscle.
METHODSThe left denervated hemidiaphragms of over 100 guinea-pigs have been used in these experiments. Most of the animals were young, weighing less than 300 g, as the in vitro survival and functional condition of the strips of diaphragmatic muscle appear to be inversely related to their thickness.The left phrenic nerve was cut in the cervical region during pentobarbitone sodium anaesthesia, and 1 week after denervation active immunization was begun by injecting antigenic proteins according to three different schedules. (1) Most of the animals were immunized to ovalbumin, human serum-albumin or
Introduction
We evaluated the value of hematopoietic progenitor cells (HPCs) counted in Sysmex XN analyzers to predict the mobilization and collection of CD34+ cells in apheresis for stem cell transplantation.
Methods
Eighty patients who underwent stem cell transplantation were enrolled (50 autologous and 30 allogeneic). In the autologous group, patients were considered poor mobilizers when the CD34+ count was <10 × 106/L or <20 × 106/L in patients with multiple myeloma who were going to undergo two transplants. ROC curves were generated, and HPC cutoffs were calculated.
Results
The correlation between the HPC and CD34+ cell counts was good. Two algorithms were proposed. In the first algorithm, samples collected the day before apheresis, negative and positive HPC cutoffs were selected to detect poor and good mobilization and, therefore, the need or not to administer plerixafor. In the second algorithm, samples collected pre‐apheresis, the negative HPC cutoff was an indication to delay apheresis; an HPC higher than the optimal cutoff was an indication to start apheresis. When the HPC values were between these cutoffs, there was an indication to count CD34+ cells for a better decision‐making. Finally, in samples collected pre‐apheresis, HPC counts could be used to predict patients who would have poor CD34+ cell collections. In the allogeneic group, all the donors mobilized well, and very few needed two apheresis procedures.
Conclusions
The HPC count is useful for decision‐making in the management of patients subjected to apheresis procedures to collect peripheral blood stem cells.
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