Surgery Section - Meniscal Allograft Transplantation

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Historically, the role of normal meniscal cartilage was greatly under appreciated and up until some 30 years ago, torn and damaged menisci were routinely excised. However, it is now known that the menisci are integral structural components of the human knee, functioning to absorb shocks, provide joint stability, congruity, and nutrition. In addition, total and partial meniscectomies are associated with altered load bearing across the joint, frequently resulting in degenerative osteoarthritis. The integrity of the menisci is particularly important in knees in which the anterior cruciate ligament (ACL) has been damaged; in these situations, the menisci act as secondary stabilizers of anteroposterior and varus-valgus translation. With this greater understanding, the surgical principles of treating torn or damaged menisci evolved to their repair and preservation whenever possible. Moreover, meniscal allograft transplantation has been investigated in patients with a previous meniscectomy or in patients requiring total or near total meniscectomy for irreparable tears.

There are three general groups of patients who have been treated with meniscal allograft transplantation:

• Those with pain and discomfort associated with early osteoarthrosis
• Those who are undergoing ACL reconstruction in whom a concomitant meniscal transplant is intended to provide increased stability
• Athletes with few symptoms in whom the allograft transplantation is intended to deter the development of osteoarthritis

The following different types of allografts have been investigated:

• Fresh

Fresh implants, harvested under sterile conditions, typically are not a practical option. The grafts must be used within a couple of days to maintain viability. Also, there are concerns regarding infectious diseases, such as HIV, and the grafts must be appropriately sized.

• Frozen

After sterile harvest, the meniscus can be frozen for storage until thawed for use. The freezing process may destroy donor cells and decrease the size of the graft.

• Freeze Dried (Lyophilized)

In addition to freezing, the tissue may be dehydrated, permitting storage at room temperature. Before transplantation, the graft is thawed and rehydrated.

• Cryopreserved

Cryopreservation freezes the graft in glycerol, preserving the cell membrane integrity and donor fibrochondrocyte viability. Of all the above options, cryopreserved grafts are most commonly used. Cryolife (Marietta, GA) is a commercial supplier of such grafts.

The risk of infectious disease, particularly HIV or hepatitis, continues to be a concern. Several secondary sterilization techniques have been used, with gamma irradiation being the most common.

Policy/Criteria

Meniscal allograft transplantation is considered investigational.

Scientific Background

Intermediate outcomes regarding meniscal allograft transplantation primarily focus on the viability of the transplanted tissue. Long-tern 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, 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.

A 1997 BlueCross BlueShield Association Technology Evaluation Center (TEC) assessment noted that the data regarding meniscal allograft transplantation are of poor quality. (1) 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 was 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 1997 does not address the limitations identified in the TEC assessment. In terms of the intermediate outcome of graft viability, the largest case series data 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 was transplanted with a bone plug for fixation, compared to 67% without such fixation. (2) The method of determining graft viability, with either serial MRI scans or second-look arthroscopy, was not reported. Additional patient outcome information is posted on their company Web site, based on responses to patient questionnaires. (3) 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. It is not possible to interpret these results scientifically due to the incomplete nature of the data and the heterogenous population of patients, many of whom presumably underwent concomitant knee reconstructive procedures.

An updated search of the MEDLINE database through July 9, 2007 identified no new studies which address the limitations noted above. In a case series 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. (5) 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. (6) While the Wirth study used two ACL control groups for comparison, the concomitant knee reconstruction does not permit scientific analysis of the contributions attributable to meniscal allograft transplantation alone. In addition, no preoperative clinical outcomes were assessed. Noyes and colleagues reported on 38 patients (40 knees) receiving cryopreserved meniscal transplant. (7, 8) At a mean of 40 months postoperative follow-up, 27 (68%) and 13 (33%) knees had no pain or mild pain, respectively, and the meniscal grafts appeared normal in 17 knees (43%) but altered in 12 (30%), and failed in 11 (28%) knees. Nevertheless, interpretation of these results is confounded since 16 knees also received concomitant osteochondral autograft transfer, and 9 had knee ligament reconstruction. The authors conclude in this study that although the short-term results of meniscal allograft are encouraging, the long-term function of the meniscal transplant "remains questionable, as the transplant appears to undergo a remodeling process that results in alterations in its collagen fiber architecture that affect its load-sharing capabilities and long-term survival." They also state that further investigation is needed to determine long-term transplant function and any chondroprotective effects. In two additional studies, Sekiya and colleagues and Yoldas and colleagues reported promising outcomes in 28 and 31 patients receiving meniscal transplants, respectively. (9,10) However, the patients in these two studies also received ACL reconstruction, again confounding interpretation of study results.

A more recent study by Verdonk and colleagues reported long-term follow-up from 100 of their first 105 (95%) fresh cultured (viable) meniscal allografts performed from 1989-2001.(11)  The indication for transplantation was moderate-to-severe pain in a younger patient (mean of 35 years, range 16 to 50 years old) who had undergone a previous total meniscectomy, was not old enough to be considered for a knee joint replacement, and had good alignment of the lower limb and a stable joint. Corrective osteotomy or stabilization was performed concomitantly on some of the joints.  Postoperative clinical evaluation was conducted yearly; 2 subjects were lost to follow-up as a result of death unrelated to the transplant (these were carried forward). With failure defined as moderate or severe pain (occasional or persistent) or poor knee function (modified Hospital for Special Surgery score of less than 80), 70% of the viable allografts (39 medial, 61 lateral) survived at 10 years, the mean survival time was estimated at 11.6 years.

This group also published follow-up of at least 10 years with radiological imaging from their first 42 allografts (27 medial, 15 lateral, treated from 1989 to 1993). (12) Of the 41 patients, 7 (17%) were followed up at the time of total knee replacement (failures); these were characterized by progression in joint space width narrowing (by 1 or 2 grades) and Fairbank changes (by 1 or 2 grades). Twenty-five allografts were evaluated in 2004 (average of 12 years follow-up). Of the 32 total cases evaluated (76% follow-up), joint space remained stable in 41% (13 of 32 knees) and Fairbank changes did not progress in 28% (9 of 32 knees). Magnetic resonance imaging (MRI) showed absence of further femoral cartilage degeneration in 8 of 17 knees (47%) evaluated. Of interest, no significant correlations were found between any of the measured radiological or MRI parameters and clinical outcome sub scales. The investigators of these reports discuss the investigational nature of this procedure and suggest a need for a prospective long-term comparison (using both subjective and objective clinical outcome measures) of patients who are treated with a meniscal allograft and a control group of patients who have similar symptoms and clinical findings. (11,12)

Sekiya and colleagues reported follow-up testing from 32 patients who underwent isolated lateral cryopreserved meniscal allograft transplantation. (13) Transplants prior to 1994 were secured with individual bone plugs (n=5), those after 1994 were secured with use of a bone bridge (n=12) or no bony fixation with nonabsorbable suture passed through transosseous tunnels (n=8), depending on surgeon preference. Twenty-five patients could be located for follow-up, 20 for postoperative radiographs, and 17 (53%) underwent complete follow-up with radiographs and examination. At an average duration of 3.3 years (range of 2 to 6 years), 96% of patients believed that their overall function and activity level were improved following surgery (13 greatly better, 7 somewhat better, 4 slightly better, and 1 somewhat worse). Radiographic evaluation showed that joint space narrowing did not progress following transplantation (pre-operative 3.70 mm, latest follow-up 3.65 mm). This was compared with a change from 6.32 mm to 6.15 mm for the contralateral non-transplanted compartment. This report is limited by the loss to follow-up of nearly half of the patient group. In a recent review, Sekiya describes meniscal allograft transplantation as a salvage procedure. (14)

Another case series reported follow-up evaluation of 39 patients, 21 menisci were transplanted in isolation, and 19 were combined with other procedures.(15)  From the whole group, 4 transplants (3 patients) failed early and another 7 had failed at follow-up, for a total 25% failure rate. The authors conclude that, “meniscus transplantation alone or in combination with other reconstructive procedures results in reliable improvements in knee pain and function at minimum 2-year follow-up. Longer term studies are necessary to determine if transplantation can prevent the articular degeneration associated with meniscectomy.”

It is notable that researchers in the area consider this to be an experimental procedure.  Heckman and colleagues conclude in their review that, “For patients in whom meniscus function has been lost from prior meniscectomy, the short-term results of meniscus transplantation are encouraging, as many patients demonstrate improvement in knee function and pain relief in the affected compartment. However, the long-term function of this operation remains questionable, as the transplant appears to undergo remodeling, which results in alterations in collagen fiber architecture required for load-sharing and survival.”(16)  Although meniscus transplantation holds promise for the younger patient, transplant procedures are evolving and it is still considered investigational. (17)

In summary, the published literature to date does not permit scientific conclusions concerning the effects of meniscal allograft transplantation on final health outcomes, particularly in the long-term. Improvements demonstrated in the short-term cannot be isolated to meniscal allograft transplantation as concomitant procedures are often performed. Further study is needed to determine long-term functional outcomes.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 7.01.15
2. TEC Assessment; Meniscal Allograft Transplantation; 1997;BlueCross and  BlueShield Association Technology Evaluation Center, Vol 12, Tab 14
3. Johnson DL, Bealle D. Meniscal allograft transplantation. Clin Sports Med 1999;18(1):93-108
4. CryoLife Web Site:  www.cryolife.com/products/ortho_meniscusnew.htm  (Verified 7/20/07)
5. Rath E, Richmond JC, Yassir W et al. Meniscal allograft transplantation. Two- to eight-year results. Am J Sports Med 2001;29(4):410-4
6. Wirth CJ, Peters G, Milachowski KA et al. Long-term results of meniscal allograft transplantation. Am J Sports Med 2002;30(2):174-81
7. Noyes FR, Barber-Westin SD, Rankin M. Meniscal transplantation in symptomatic patients less than fifty years old. J Bone Joint Surg Am 2004;86-A(7):1392-404
8. Noyes FR, Barber-Westin SD, Rankin M.  Meniscal transplantation in symptomatic patients less than fifty years old.  JBone Joint Surg Am  2005;87 Suppl 1(pt 2):149-65
9. Sekiya JK, Giffin JR, Irrgang JJ, et al. Clinical outcomes after combined meniscal allograft transplantation and anterior cruciate ligament reconstruction. Am J Sports Med 2003;31(6):896-906
10. Yoldas EA, Sekiya JK, Irrgang JJ, et al. Arthroscopically assisted meniscal allograft transplantation with and without combined anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 2003;11(3):173-82
11. Verdonk PC, Demurie A, Almqvist KF et al. Transplantation of viable meniscal allograft. Survivorship analysis and clinical outcome of one hundred cases. J Bone Joint Surg Am 2005; 87(4):715-24
12. Verdonk PC, Verstraete KL, Almqvist KF et al. Meniscal allograft transplantation: long-term clinical results with radiological and magnetic resonance imaging correlations. Knee Surg Sports Traumatol Arthrosc 2006; 14(8):694-706
    
13. Sekiya JK, West RV, Groff YJ, et al. Clinical outcomes following isolated lateral meniscal allograft transplantation. Arthroscopy 2006; 22(7):771-80
14. Sekiya JK, Ellingson CI. Meniscal allograft transplantation. J Am Acad Orthop Surg. 2006; 14(3):164-74
    
15. Cole BJ, Dennis MG, Lee SJ, et al. Prospective evaluation of allograft meniscus transplantation: a minimum 2-year follow-up. Am J Sports Med 2006; 34(6):919-27
16. Heckmann TP, Barber-Westin SD, Noyes FR. Meniscal repair and transplantation: indications, techniques, rehabilitation, and clinical outcome. J Orthop Sports Phys Ther 2006 Oct;36(10):795-814
17. Eriksson E. Meniscus transplantation. Knee Surg Sports Traumatol Arthrosc 2006; 14(8):693

Cross References

None

Surgery Section Table of Contents