Factors affecting the efficiency of peripheral blood stem cell collection in children treated with chemotherapy and G-CSF

This retrospective study attempts to clarify the optimal timing for peripheral blood stem cell (PBSC) collection after conventional chemotherapy followed by granulocyte-colony stimulating factor (G-CSF) administration. Leukapheresis was performed 32 times in nine children with various cancers during bone marrow recovery phase following transient pancytopenia after chemotherapy. (On two occasions, leukapheresis was excluded because many leukemic blasts were included.) When the number of white blood cells (WBC) exceeded 1.8 times 10¹⁰/L after administration of G-CSF (200 μg/m², continuous infusion), many more CD34⁺ cells were contained in the collected peripheral mononuclear cells (P > 0.02) and a sufficient number of PBSC for transplantation (≥ 10 times 10⁸ CD34⁺ cells/kg) was obtained after one run in 15 of 17 leukapheresis sessions. In contrast, sufficient PBSC were obtained only in one of 13 runs of leukapheresis when the number of WBC was < 1.8 times 10¹⁰/L. The number of WBC on the day when PBSC were collected correlated with collected nuclear cell number (r = 0.60), but not with the CD34⁺ cell ratio. The ratio was higher only when both platelets and reticulocytes increased in parallel with WBC. We conclude that sufficient PBSC collection is possible after conventional chemotherapy using G-CSF, when hematopoietic recovery is parallel, without the use of high-dose chemotherapy.     

Shortcut Link Between the Fast and Slow Pathways and the Mechanism of Cure in Atrioventricular Nodal Reentrant Tachycardia by Catheter Ablation

The mechanism of cure in AV nodal reentrant tachycardia (AVNRT) by catheter ablation has not been fully clarified. We hypothesized that disruption of a shortcut link between the fast and slow pathways is responsible for the elimination of tachycardia. Results: AVNRT was eliminated in 20 patients by catheter ablation. In five patients (25%; group 1) slow pathway conduction disappeared 1 week after ablation. In six patients (30%; group II), the effective refractory period of the slow pathway was prolonged by more than 50 ms (212 ± 81 ms vs 340 ± 81 ms; P < 0.05). In the remaining nine patients (45%; group III), there was no change in the refractory period (270 ± 65 ms vs 273 ± 74 ms), although tachycardia was not inducible. A shortcut link between the fast and slow pathways was examined by comparing the A-H intervals over the slow pathway during the tachycardia and during atrial pacing at the tachycardia cycle length. Prior to ablation, a shortcut link was assumed in 1 of group I patients, 2 of group II patients, and 8 of group III patients. Of the 9 patients in whom the slow pathway was not impaired after ablation (group III), 8 patients were found to have a shortcut link, while 8 of 11 patients with impairment of the slow pathway after ablation (groups I and II) had no shortcut link between the fast and slow pathways (P < 0.05). Conclusion: In patients with a shortcut link between the fast and slow pathways, slow pathway conduction itself does not need to be impaired to eliminate the AVNRT, whereas in patients without this shortcut link, slow pathway conduction must be impaired.     

Myeloid differentiation is impaired in transgenic mice with targeted expression of a dominant negative form of retinoid X receptor β

To investigate the in vivo function of retinoid X receptor (RXR) on myelopoiesis, we generated transgenic (Tg) mice with targeted expression of a dominant negative form of RXR β in myeloid cells. In these Tg mice the transgene is expected to suppress the function of heterodimeric receptors composed of RXR and its counterparts, such as retinoic acid receptor. Out of 12 mice analysed, one Tg mouse exhibited a severe maturation arrest at the promyelocytic stage. Three other Tg mice showed a mild inhibition of myeloid differentiation, which was further augmented when mice were treated with 5-fluorouracil (5-FU). Furthermore, four Tg mice showed impaired myeloid differentiation in response to the treatment by 5-FU or granulocyte-colony stimulating factor (G-CSF), although they exhibited apparently normal myelopoiesis in the untreated state. The phenotype of Tg mice observed after G-CSF treatment correlated with the expression level of the transgene, although the correlation was not found in untreated mice. These results indicated that myeloid differentiation is perturbed in the Tg mice by the dominant negative effect of the transgenic RXR, indicating that RXR plays a role in myelopoiesis.