Efficacy and safety of stem cell mobilization with cyclophosphamide plus etoposide versus cyclophosphamide alone.

The use of the combination of two cytostatics cyclophosphamide (CTX) and etoposide (VEP) and G-CSF is a reasonable alternative, especially for stem mobilization in multiple myeloma (MM) patients from countries in which newer treatments are limited due to financial constraints. The aim of this study was to compare the efficacy and safety of CTX-VEP versus CTX alone for mobilization of hematopoietic stem cells in MM patients. The analysis included 48 consecutive MM patients mobilized with CTX-VEP compared to 43 consecutive historical controls mobilized with CTX alone. The two groups of MM patients did not differ in terms of the median number of apheresis procedures, median yield the first day, median numbers of harvested CD34+ cells, proportion of patients with at least 5 x 106/kg yield and incidence of non-hematological complications. The median cumulative dose of G-CSF given to individuals in the CTX-VEP group was significantly lower than in the CTX group (p < 0.001). The incidence of post-mobilization thrombocytopenia was higher in the CTX group (p<0.001). The median time to platelet count > 20 x 109/l (10 vs. 11 days, p = 0.004) and the median time to neutrophil count > 50 x 109/l (11 vs. 13 days, p < 0.001) were significantly shorter among the patients mobilized with CTX-VEP than in those treated with CTX alone. These findings suggest that CTX-VEP is as efficacious and possibly safer than CTX alone.

Transcoronary stem cell delivery using physiological endothelium-targeting perfusion technique: the rationale and a pilot study involving a comparison with conventional over-the-wire balloon coronary occlusions in patients after recent myocardial infarction.

INTRODUCTION: Recent evidence shows poor efficacy of over-the-wire balloon catheter (OTW) coronary occlusive technique adopted widely for intracoronary bone marrow stem cell (BMSC) delivery. The waterfall effect of OTW-balloon inflation/deflation with reactive > or = 2-fold flow velocity increase might be partly responsible for poor BMSC retention. AIM: To evaluate the safety, feasibility and tolerability of perfusion-infusion BMSC delivery with the facilitation of cell rolling in contact with the coronary endothelium (a pre-requisite for downstream transmigration). METHODS: We randomly assigned 11 patients (age 41-72 years) with first anterior myocardial infarction treated with PTCA+stent and LVEF < or =45% at 6-9 days to OTW in-stent occlusive (3 x 3 min.) BMSC delivery or cell infusion via a perfusion catheter with multiple side holes (SH-PC). RESULTS: OTW and SH-PC patients had a similar infarct size (mean peak CK 4361 vs 4717 U/L), LVEF (41.2% vs 40.3%), infused mononuclear cell number (2.99 x 108 range 0.61-7.48 x 108 vs 3.28 x 108 range 1.64-4.39 x 108), CD 34(+) number (1.79 x 106 vs 1.62 x 106), cell viability (91.5% vs 91.8%) and clonogenicity (CFU assay). None of the SH-PC, but 67% of OTW patients, had ST-segment elevation with chest pain (and nsVT in one) that limited OTW occlusion tolerance to 50-110 sec. At 6 months DLVEF in the OTW vs SH-PC patients was +4.2% (2-6) vs +8.8% (5-16) by MRI and +4.8 (2-7) vs +13.8% (2-24) by SPECT. CONCLUSIONS: Our work indicates that the SH-PC technique can be used safely for intracoronary BMSC transplantation. Further research is needed to determine whether the putative advantages of physiological SH-PC delivery translate into enhanced BMSC homing.