LCD/NCD Portal

L33015 TRANSPLANTATION IMMUNE CELL FUNCTION ASSAY (IMMUKNOW®)

 

 

01/29/2013

 

Indications and Limitations of Coverage and/or Medical Necessity

 

• The purpose of this local coverage determination (LCD) is to communicate that after review of the strongest available evidence, it has been determined that the Transplantation Immune Cell Function Assay (ImmuKnow®) does NOT meet reasonable and necessary criteria as defined in Section 1862 (a)(1)(A) of the Social Security Act.

• Section 1862(a)(1)(A) of the Social Security Act precludes program payment for services not deemed to be medically reasonable and necessary.

• A service or item is considered to be reasonable and necessary if it is:

o Safe and effective;

o Appropriate, including the duration and frequency that is considered appropriate for the service, in terms of whether it is:

 Furnished in accordance with accepted standards of medical practice for the diagnosis or treatment of the patient’s condition or to improve the function of a malformed body member;

 Furnished in a setting appropriate to the patient’s medical needs and condition;

 Ordered and furnished by qualified personnel

 One that meets, but does not exceed, the patient’s medical need; and

 At least as beneficial as an existing and available medically appropriate alternative

 

 

Background

 

• Both solid organ (kidney, heart, liver, lung, and integument) and hematopoietic stem cell transplantation are interventions which place beneficiaries at high risk.

o Among the risks are opportunistic infection, induction of malignancy, and the multi-system morbidity of immune transplant rejection.

• Laboratory tests to predict rejection (incompatibility) between transplant donors and recipients measure two separate aspects of immunity to predict future graft success:

o humoral immunity (measuring circulating antibodies directed against the graft) and

o cell-mediated immunity or CMI (measuring cellular anti-transplant rejection risk by lymphocytes, macrophages, and other cell types which reside in the marrow, spleen, lymph nodes, and circulation).

• A variety of tests of CMI are in common use for testing the immune systems of potential and post-operative transplant recipients.

o The most popular and informative are the CD4- and CD8-cytotoxic CMI tests, which have high sensitivity, specificity, positive and negative predictive value for the patient’s risk of “cellular rejection.”

• It is common practice in transplant centers to test transplant candidates for risk of cellular rejection pre- and post-transplant.

o In addition, when a transplant recipient exhibits signs of inflammation and acute illness, it is critical to differentiate three different potential processes, which mandate different therapeutic approaches: acute infection (which may be of an uncommon, “opportunistic” type), medication toxicity (especially the inflammatory syndromes caused by Cyclosporine toxicity), and true graft rejection.

• The precision of tests to differentiate these graft- and life-threatening processes is critical.

o Transplant physicians must stratify test selection based on informative properties.

o Any lab test(s) which fail to provide maximum resolution among the above syndromes must be disqualified from use for pre-transplant candidates or recipients.

 

 

Assessment of the Transplantation Immune Cell Function Assay (ImmuKnow®)

 

• The following summarize studies which endeavored to establish correlation between ImmuKnow test results and transplant and/or infection risks:

o Large series reported by Cadillo-Chavez, et al (2006) failed to demonstrate statistically significant relationships between ImmuKnow ATP levels and risk of infection and/or rejection episodes.

o Another report (Batal, et al, 2008) likewise failed to establish a predictive correlation between ImmuKnow levels, viral infection events, and risk of rejection.

o Serban, et al (2009) assayed the range of ATP values generated by ImmuKnow testing and failed to demonstrate a correlation to clinical rejection and likewise failed to be informative for immunosuppression dosing changes.

o Bhorade, et al (2008) studied a large cohort of lung transplant patients and failed to observe a relationship between levels of immunosuppression, risk of infection, and ImmuKnow dosing.

o Rossano, et al (2009) tested for correlation between the ImmuKnow assay and the risk of pediatric heart transplant rejection events. The authors failed to demonstrate a correlation and concluded the test cannot be recommended for routine use in this critical setting for these vulnerable patients.

o Torio, et al (2011) did demonstrate a correlation between ImmuKnow test outcomes in infected and non-infected transplant patients; however, the test exhibited no predictive value for transplant organ rejection risk.

• ImmuKnow is NOT reasonable and necessary for the management of organ transplant rejection.

o There is insufficient evidence of the effectiveness of the ImmuKnow assay in the management of organ transplant rejection in individuals undergoing immunosuppressive therapy post solid organ transplant and for the identification of individual risk for rejection prior to kidney or any other solid organ transplant.

• The use of ImmuKnow assay is not reasonable and necessary to indicate risk of underlying active infection.

o ImmuKnow has not been proven to be at least as beneficial as an existing and available medically appropriate alternative.

o  Both active infection and cellular rejection may be more accurately assessed by alternative, proven and superior lab testing modalities.

o ImmuKnow is not reasonable and necessary for the individualized titration of immunosuppressive therapy.

o There is insufficient evidence that the results of immune cell function testing will result in improved clinical outcome in individuals following solid organ transplant.

o ImmuKnow is not reasonable and necessary to identify individuals at risk for rejection prior to kidney or any other solid organ transplant or for the management of other conditions.

o The utility of the assay is unproven for these uses.

• Use of the Immune Cell Function Assay to monitor and predict immune function after solid organ transplantation and to detect or predict risk of active infection does not attain reasonable and necessary criteria for coverage.

 

 

CPT/HCPCS Codes

 

86352 CELLULAR FUNCTION ASSAY INVOLVING STIMULATION (EG, MITOGEN OR ANTIGEN) AND DETECTION OF BIOMARKER (EG, ATP)

 

 

Documentation Requirements

 

• In order for the non-covered service listed in this Local Coverage Determination (LCD) to be evaluated for coverage, a reconsideration request must be submitted in writing to First Coast Service Options Inc., Medical Policy Department.

• Copies of published full-text evidence (e.g., peer-reviewed medical literature, published studies, etc.) must also be included with the reconsideration request.

 

 

Sources of Information and Basis for Decision

 

Aetna Policy Number 0773, Clinical Policy Bulletin: ImmuKnow (Transplantation Immune Cell Function Assay). Retrieved from http://www.aetna.com/cpb/medical/data/700_799/0773.html (last review 12/02/2011).

 

Anthem Medical Policy Number LAB.00024, Immune Cell Function Assay. Retrieved from http://www.anthem.com/medicalpolicies/policies/mp_pw_b088847.htm (last review 5/10/2012).

 

Batal I, Zeevi A, Heider A, et al. Measurements of global cell-mediated immunity in renal transplant recipients with BK virus reactivation. Am J Clin Pathol. 2008;19(4):587-591.

 

BCBS of Idaho Medical Policy Number MP 2.04.56, Immune Cell Function Assay. Retrieved from https://www.bcidaho.com/providers/medical_policies/Med/mp_20456.asp (last review 11/2011).

 

BCBS of Delaware Medical Policy Number 10.01.Z-24, Miscellaneous Services (last review 6/12/12). Retrieved from https://www.bcbsde.com/ProviderPolicies/public_site/10.01.Z-24_Miscellaneous_Services.htm.

 

BCBS of North Carolina Medical Policy for Immune Cell Function Assay. Retrieved from http://www.bcbsnc.com/assets/services/public/pdfs/medicalpolicy/immune_cell_function_assay.pdf (last review 3/2012).

 

Bhorade SM, Janata K, Vigneswaran WT, et al. Cylex ImmuKnow assay levels are lower in lung transplant recipients with infection. J Heart Lung Transplant. 2008;27(9):990-994.

 

Cadillo-Chavez R, de Echegaray S, Santiago-Delpin EA, et al. Assessing the risk of infection and rejection in Hispanic renal transplant recipients by means of an adenosine triphosphate release assay. Transplant Proc. 2006;38(3):918-920.

 

Centers for Medicare & Medicaid Services (CMS) General Background on Transplant Patient Management:

 

1.CMS Medicare National Coverage Determinations (NCD) Manual (IOM Pub. 100-03, Chapter 1, Part 4,) §260-260.9 concerning solid organ transplants; (Retrieved from http://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Downloads/ncd103c1_Part4.pdf).

 

2.CMS Policy (Ruling CMS-1543-R) concerning the proper allocation of donor acquisition costs incurred by organ procurement organizations (OPOs) and acquisitions involved. (Retrieved from http://www.cms.gov/Regulations-and-Guidance/Guidance/Rulings/downloads/CMS1543R.pdf).

 

Food and Drug Administration (FDA) 510(K) approval for Cylex Inc. Immune Cell Function Assay (i.e., ImmuKnow®). Retrieved from http://www.accessdata.fda.gov/cdrh_docs/pdf10/K101911.pdf.

 

Immunology of Transplant Rejection. Review of Transplant Immunobiology; Retrieved from http://emedicine.medscape.com/article/432209-overview#aw2aab6b7.

 

Lab Tests Online; a peer-reviewed, non-commercial lab test resource. HLA Testing; Retrieved from http://labtestsonline.org/understanding/analytes/hla-testing/tab/test.

 

Rossano JW, Denfield SW, Kim JJ, et al. Assessment of the Cylex ImmuKnow cell function assay in pediatric heart transplant patients. J Heart Lung Transplant. 2009;28(1):26-31.

 

Serban G, Whittaker V, Fan J, et al. Significance of immune cell function monitoring in renal transplantation after Thymoglobulin induction therapy. Hum Immunol. 2009;70(11):882-890.

 

Torio A, Fernandez E, Montes-Ares O, et al. Lack of association of immune cell function test with rejection in kidney transplantation. Transplant Proc. 2011;43(6):2168-2170.

 

Transplant Tests and Evaluations. Review of standard transplant clinical and laboratory testing; Retrieved from http://www.kidneylink.org/TransplantTestsAndEvaluations.aspx.

 

01/29/2013

The official local coverage determination (LCD) is the version on the Medicare coverage database at www.cms.gov/medicare-coverage-database/.

 

 

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CPT codes, descriptions and other data only are copyright 2012 American Medical Association (or such other date of publication of CPT). All Rights Reserved. Applicable FARS/DFARS Clauses Apply. Current Dental Terminology, (CDT) (including procedure codes, nomenclature, descriptors and other data contained therein) is copyright by the American Dental Association. © 2002, 2004 American Dental Association. All rights reserved. Applicable FARS/DFARS apply.

 

CMS LCD TRANSPLANTATION IMMUNE CELL FUNCTION ASSAY (IMMUKNOW®)