Intermediate outcomes regarding meniscal allograft transplantation primarily focus on the viability of the transplanted tissue. Long-term outcomes vary with the patient population studied. For example, relief of pain and improved function are critical outcomes for symptomatic patients with signs and symptoms of osteoarthritis. When performed in conjunction with repair of the anterior cruciate ligament (ACL), improved function and maintenance of knee stability is pertinent. In both of the above situations, it is important to isolate the contribution of the meniscal allograft to the overall surgical procedure. Finally, for asymptomatic patients who are undergoing allograft transplantation prophylactically, long-term outcomes regarding the incidence of subsequent osteoarthritis is important.

 

Data regarding meniscal allograft transplantation are of poor quality.  For example, none of the studies reporting health outcomes included preoperative and postoperative measures of restoration of knee function, including MRI results or second-look arthroscopy. None of the studies presented clear comparisons of preoperative clinical findings to postoperative results. Each study assessed outcomes differently. While definitive data were not available, in general, poor results were reported in patients with Outerbridge grade III or IV osteoarthritis, or in those with unstable knees, and thus researchers have largely abandoned meniscal allograft transplantation in these patients.

 

The literature published since the 1997 Assessment does not address the limitations identified in the Blue Cross Blue Shield Association Technology Evaluation Center Assessment. In terms of the intermediate outcome of graft viability, the largest case series has been collected by CryoLife, a commercial supplier of cryopreserved allografts. However, these data are not available in the published peer-reviewed literature. As summarized by Johnson in a 1999 report, among 1,023 transplants, CryoLife reported graft survival of 93% when the meniscus is transplanted with a bone plug for fixation, compared to 67% without such fixation.  The method of determining graft viability, with either serial MRI scans or second-look arthroscopy, is not reported. Additional patient outcome information is posted on their company Web site, based on responses to patient questionnaires.  A total of 332 patients were contacted; 136 (41%) responded. The mean patient age was 35 years old, and in 84% of cases transplantation was related to prior sports or traumatic injury. A total of 80% of patients rated their knee function as normal to nearly normal as compared to their knee function before surgery. The incomplete nature of the data and the heterogeneous population of patients, many of whom presumably underwent concomitant knee reconstructive procedures, make this data scientifically uninterpretable.

 

A review of the peer-reviewed literature on MEDLINE for the period of 2001 through February 2003 found no articles addressing the study limitations noted above. In a case study of 23 patients, Rath and colleagues reported significant improvement in function and reduced pain as measured by the Short Form-36 scores after cryopreserved meniscal allograft transplantation for compartmental pain after total meniscectomy 2-8 years post-operatively.  However, the authors noted function remained limited, and 8 of 22 allografts tore during the study period and required total or partial meniscectomies. In a prospective study of 23 patients who underwent medial meniscal transplantation with reconstruction of the ACL, Wirth and colleagues reported better results in the 6 cases of preservation of deep-frozen allografts over lyophilized meniscal transplants at 3 and 14 years postoperatively.   While the Wirth study used 2 ACL control groups for comparison, the concomitant knee reconstruction does not permit scientific analysis attributable to meniscal allograft transplantation alone. In addition, no preoperative clinical outcomes were assessed. Therefore, these 2 studies do not alter the findings above and the policy statement is unchanged.

 

A paper on "current concepts" on Meniscus allograft transplantation by Lubowitz, PC Verdonk, JB Reid III, and R Verdonk published in May 2007 was reviewed. The authors stated, "A growing body of evidence suggests that pain relief and functional improvement may reliably be achieved at short- and medium-term follow-up, and even, in some cases, at long term (>10 years) follow-up.  Future research must address the issue of optimal timing of the procedure and whether meniscal transplantation results in demonstrable long-term benefits, especially with regard to protection of articular cartilage."  

 

Two articles by Sekiya et al and Rankin et al were reviewed.  All articles reported retrospective studies with small numbers of patients and short follow-up periods. Sekiya et al,  in 2003, concluded a prospective randomized controlled study would be necessary to definitively prove the impression that restoration of meniscal function would provide protection for the articular cartilage and improve joint stability.

 

R Verdonk, KF Almqvist, W Huyesse, and PC Verdonk published another review in September 2007, stating, "…the major drawback in all meniscus allograft studies is the general lack of a control propulation."

 

Another September 2007 article by G von Lewinski, et al., reporting their 20 year experience with meniscal allograft transplantation described that radiological results revealed clear degenerative changes with long-term follow-up after meniscal allograft transplantation even though some patients did relatively well regarding the subjective and clinical results…in comparison with the literature.

 

In 2007, Matava published a systematic review of the available literature; none of the 15 studies identified could be classified as Level I or Level II (prospective controlled comparisons), 3 studies qualified as Level III (retrospective comparisons); the 12 remaining studies were retrospective case series.  The primary indication for meniscal allograft transplantation in these studies was complete or near-complete meniscectomy with pain in the involved compartment, and before the development of moderate to severe arthrosis (less than 2 to 3 mm of joint space narrowing and/or limited chondral wear) in a young (less than 50 years of age) active patient. Lower extremity malalignment and/or ligamentous instability have been associated with meniscal transplantation failure, and thus were treated (e.g., osteotomy or ACL repair) before or at the time of the transplantation. Twelve studies used validated outcome measures, with second-look arthroscopy conducted in some of the patients in 11 studies. “Success” rates were usually over 60% (ranging from 13% to 100%), with more recent series reporting short-term favorable outcomes (based on pain, function, and patient satisfaction) in about 85% of their patient cohorts (generally 20 to 30 patients per cohort). Up to 26% reoperation rates for allograft tears in addition to other complications were reported. Matava et al noted that fresh frozen or cryopreserved grafts were associated with the highest success rates and the least risk for biomechanical degradation or disease transmission.

 

Also, in 2007, Hommen and colleagues reported 10-year follow-up on 20 of 22  consecutive patients who received cryopreserved meniscus allografts.   The 10-year graft survival/success rate was 45%, with 5 allograft failures identified on second-look surgery, 5 allografts with grade III tears identified on magnetic resonance imaging (MRI), and 4 patients reporting no improvement. Of 15 patients with follow-up radiographs, 10 had narrowing and 12  had progression of the Fairbank degenerative joint disease score  in the transplanted tibiofemoral compartment. Twenty-year follow-up was reported for 5 patients who had received a deep frozen meniscal allograft along with other procedures on the knee (Lewinski et al, 2007).  At 20-year follow-up MRI revealed shrinkage of the transplants with very small rims of the meniscus; the remaining meniscal tissue showed degenerative changes. As noted by Hommen et al, questions remain about whether meniscus grafts can delay or prevent the progression of degenerative changes and joint space narrowing (Hommen et al, 2007).

 

In summary, meniscal allograft transplantation appears to improve symptoms in some patients with a prior meniscectomy who are considered too young to undergo total knee replacement.   Evidence consisting primarily of retrospective case series indicates that this procedure may produce short- term to intermediate-term pain relief in selected patients.   At this time, there are no long-term controlled studies.  The literature does not permit conclusions concerning the effect of meniscal transplantation on the progression of degenerative changes and joint space narrowing.   

 

Meniscal allograft transplantation is associated with a high number of complications, including tears of the transplanted meniscus, displacement, or arthrofibrosis.  In addition, the risk of infection from cadaver transplant has not been completely resolved.  Careful selection of patients and surgical technique appear to be critical for success of this procedure.

 

In 2006, a German research group published initial results from a randomized trial that compared high tibial valgus osteotomy alone with osteotomy plus a collagen meniscus implant in 60 patients with subtotal loss of the medial meniscus (Linke, 2006).  Arthroscopy on the first 23 of 30 patients with a collagen implant at 8-18 months post-surgery showed complete healing in 8 patients (35%), partial healing in 7 (30%; requiring resection of the posterior part of the implant), and poor results with only small remains of the collagen implant left in 8 patients (35%). Complications included implantation in insufficiently vascularized tissue, sutures cutting into the implant, inadequate fixation to the rim, destruction of the implant in an unstable knee joint or with premature loading post-operatively, allergic reaction to the xenogenic collagen implant, avulsion of the implant with joint blocking, and infection. Assessment of pain and function (Lysholm, International Knee Documentation Committee, subjective pain scores) showed slight and non-significant differences in comparison with the 16 patients treated with correction osteotomy only. Longer follow-up on all 60 patients is reported to be continuing.

 

Data provided to the FDA in support of the 510(k) application for the Menaflex collagen meniscus implant included a prospective, randomized multicenter clinical trial (26 surgeon-investigators from 16 sites) that was conducted under an investigational device exemption (IDE) and published in 2008 (Rodkey, 2008).  The study involved 311 patients, randomized and analyzed separately for those with no prior surgery (acute group, n = 157) and those who had from 1 to 3 prior meniscal procedures (chronic group, n = 154). Included were patients 18 to 60 years of age who had an irreparable injury to or previous partial loss of one medial meniscus, with an intact rim. The involved knees had to be in neutral alignment, and patients with a fullthickness (Outerbridge Grade-IV) chondral lesion were excluded from the study, as were patients with posterior cruciate ligament insufficiency. Patients within the acute and chronic arms were randomized to receive the collagen meniscus implant or be treated with a partial meniscectomy only. Control patients (partial meniscectomy only) underwent standard physical therapy only. Patients receiving a collagen meniscus implant wore a knee brace that was locked in full extension for 6 weeks and were required to be non-weight-bearing with crutches for 2 weeks. The brace was removed 3 to 4 times per day to perform self-assisted passive range-of-motion exercises. Full weight-bearing and unlimited active and passive range-of-motion exercises were initiated after 6 weeks. Second-look arthroscopy with biopsy at one year was performed for all patients who received a collagen meniscus implant (acute and chronic); 141 of 160 patients in the 2 groups (88%) had arthroscopy. Patients underwent frequent clinical follow-up examinations over 2 years and completed validated outcomes questionnaires for up to 7 years (Lysholm functional score, Tegner activity scale and pain on a visual analog scale). At an average follow-up of 59 months (range, 16-92), new tissue was reported to appear grossly meniscus-like and integrate with the meniscus rim, with about 50% of the defect filled (45% in the acute group and 58% in the chronic group). There were no differences between the implant and control groups for pain, Lysholm and self-assessment scores. Only Tegner activity scores in the chronic arm were significantly different, with patients in the implant group reporting regaining 42% of their lost activity level, compared to a 29% regain in activity reported by controls. Implant patients in the chronic group underwent significantly fewer non-protocol reoperations (8 vs. 15) compared to controls, although the report did not indicate whether procedures other than a “re-look” were performed during the one-year protocol scheduled reoperation. No differences were detected between the 2 treatment groups in the acute arm of the study, with 5 reoperations in each group. Kaplan-Meier analysis, which was estimated at 5 years due to the low number of patients at risk, suggested a modest increase in survival in the chronic group who had received a collagen implant compared to controls (about 90% vs. 80%). Longer follow-up is needed to determine whether implantation of a collagen scaffold is able to slow joint degeneration, reduce pain, or otherwise improve the net health outcome at longer durations. Controlled studies comparing the collagen meniscus implant with allograft transplantation would also be of value in evaluating the health benefit of this procedure. The evidence at this time is insufficient to permit conclusions concerning the effect of this technology on health outcomes.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

    

 

 

 

 

 

 

 

 

 

 

 

A literature review conducted using the MEDLINE database did not reveal any new literature that would prompt a change in the coverage statement. There were no new randomized controlled trials identified.