I started reviewing in the last post details from the publication of the three-year milestone outcomes for a clinical study on treating degenerative disc disease with BMC.
The details concerning the patient demographics, and how patients were enrolled in the study are described in the first-year milestone publication by Pettine, et al. (2015). The salient points are that all patients were seen for lower back pain, and subsequently had failed conservative treatment for a minimum of three to six months. Patients meeting these criteria, and other exclusion/inclusion criteria, were provided with an option to receive an autologous BMC injection into the pathologic disc(s), or undergo spinal fusion/artificial disc replacement.
As reported in the first-year milestone publication, the BMC preparations on which analysis was performed had an average total of 121 x 106 nucleated cells/mL in the injectate. These preps also had an average of 2,713 CFU-F colonies/mL in the injectate. CFU-F stands for colony forming unit-fibroblast and is considered to be a biomarker estimate of the MSC content. Eight of 20 patients who had had an MRI of the pathologic disc at one-year showed an improved level of hydration of the pathologic disc(s), such that a blinded reader indicated that according to the modified Pfirrmann score (a multi-factor assessment of disc health) these patients showed an improvement of a single grade (i.e., a lower score). Perhaps equally as important was the fact that none of the other 12 patients showed a degradation in disc status sufficient to increase their Pfirrmann score.
The availability in the clinical study of an estimate of the MSC content for the BMC injectates in the study, along with the clinical outcome metrics of Visual Analog Score (VAS) and Oswestry Disability Index (ODI) created an opportunity to look for correlations between MSC content and improvement in VAS and/or ODI. As reported in the first-year milestone paper, there was an obvious correlation between percent improvement in VAS and ODI and the concentration level of MSCs in the injectate. In fact, a level of 2,000 CFU-F/mL of injectate emerged as a useful breakpoint for tracking clinical outcomes over three years. When this breakpoint was examined in the first-year milestone paper, there seemed to be a somewhat faster improvement in VAS and ODI for patients receiving >2,000 CFU-F/mL at earlier time points (3 and 6 months) compared to the patients receiving <2,000 CFU-F. However, regardless of the number of CFU-Fs a patient received, the majority of improvement was achieved between three and six months post-injection.
Out of 26 patients at the start of the study, two patients elected to have surgery within the first 12 months, so 24 of 26 patients remained active at 12 months. Another three patients progressed to surgery between 12 and 24 months, while one patient opted for surgery between 24 and 36 months. Thus, over the three-year period 77% of the patients initially receiving BMC injections into their pathologic discs remained in the study. Of particular interest to me is the fact that three of the six surgical patients were treated at a single level, while the other three had two levels injected. I was surprised at this result, since I would have expected patients with two-level pathology to be at a higher risk of surgical progression, since, after all, they have twice the chance for a disc to become painful again. What this suggests is that treating two adjacent pathologic discs with BMC might provide a synergistic benefit, thereby reducing the potential for return of pain to either disc. So, my original concern about including patients with 2-level disc pathology in the clinical study proved to be unfounded.
I will finish up my review of the three-year milestone publication in the next post.