Solid Organ and Hematopoietic Stem Cell Transplantation Laboratory Testing for Donors and Recipients

Solid Organ and Hematopoietic Stem Cell Transplantation Laboratory Testing for Donors and Recipients

This Test Guide discusses the use of laboratory tests that help match donors and recipients for solid organ and bone marrow transplantation, and also discusses tests that identify and monitor infectious disease in post-transplant recipients.

Solid Organ and Hematopoietic Stem Cell Transplantation: Laboratory Testing for Transplant Recipients

Test Guide

 

Solid Organ and Hematopoietic Stem Cell Transplantation

Laboratory Testing for Donors and Recipients

This Test Guide provides a description of tests available for transplant donors and recipients. Laboratory testing includes US Food and Drug Administration (FDA)-required testing of donors for certain infectious diseases,1 testing for genetic kidney diseases to evaluate donor candidates,2 guideline-indicated compatibility testing (human leukocyte antigen [HLA] typing and HLA antibody screening) for transplant donors and recipients,3 and post-transplant testing to monitor immunosuppressive and antifungal drug therapies and follow-up for infectious disease.

This Test Guide is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.

Donor testing

Laboratory testing can help avoid transmission of infectious disease through transplanted human cells, tissues, and cellular-based products (HCT/Ps) by identifying diseases or disease agents in potential donors with active or latent infections; immunosuppressive drugs used to prevent transplant rejection can reactivate latent infections.4

The FDA requires testing of all donors of HCT/Ps for infections including HIV-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum (syphilis); testing for West Nile virus (WNV) is required for living donors.1 Depending on HCT/P type, requirements may also include testing for human T-lymphotropic virus (HTLV), cytomegalovirus, Chlamydia trachomatis, Neisseria gonorrhea, and Trypanosoma cruzi, the parasite that causes Chagas disease (Table 1).5,6

For potential living kidney donors who self-report African ancestry, detection of any 2 APOL1 risk alleles (G1/G1, G2/G2, or G1/G2) indicates an increased risk for developing APOL1-associated chronic kidney disease. The risk of premature allograft loss associated with a high-risk genotype in a living donor is currently unknown, but a high-risk genotype in a deceased donor is associated with shorter allograft survival in transplant recipients.7,8

Quest Diagnostics offers a menu of pretransplant tests that includes APOL1 renal risk variant genotyping and donor screening panels for infectious diseases (Table 1); components of panels can be ordered separately. These panels, based on FDA guidelines for approved testing,5,9 include tests for HIV-1/2, HBV, HCV, CMV, T pallidum, and others.

Table 1. APOL1 Risk Variant and Infectious Disease Testing for Donors

Test code

Test name

 

Primary clinical use

Genotyping

1291

Apolipoprotein L1 (APOL1) Renal Risk Variant Genotyping

 

Assist evaluation of a potential donor for kidney transplantation

Infectious disease testing

91986

Donor, Chagas Screen

 

Screen for Trypanosoma cruzi infection in potential donors of HCT/Ps

17385

Donor, Chlamydia trachomatis/Neisseria gonorrhoeae, RNA, TMA

 

Screen for C trachomatis and N gonorrhoeae RNA in potential donors of reproductive HCT/Ps

17388

Donor, Cytomegalovirus Antibody, Total

 

Screen for CMV infection in potential donors of viable, leukocyte-rich cells or tissues

90557

Donor, Cytomegalovirus Antibody, Total With Reflex to (IgG, IgM)a

 

Screen with reflex to diagnostic testing for CMV infection in potential donors of viable, leukocyte-rich cells or tissues

19618

Donor, Cytomegalovirus Antibody Total With Reflex Non-donor CMV IgMa

17378

Donor, Hepatitis B Core Total Antibody

 

Screen for history of HBV infection in potential donors of HCT/Ps

17375

Donor, Hepatitis B Surface Antigen With Reflex to Confirma

 

Screen and confirmation for acute or chronic HBV infection in potential donors of HCT/Ps

93305

Donor, Hepatitis C Antibody (Anti-HCV)

 

Screen for acute or chronic HCV infection in potential donors of HCT/Ps

19854

Donor, HIV/HCV/HBV NAT Procleix® With Reflexesa

 

Screen for HIV-1 RNA, HIV-2 RNA, HCV RNA, and HBV DNA in potential donors of HCT/Ps

17380

Donor, HIV-1/2 Plus O Antibody Screen

 

Screen for HIV-1 and HIV-2 infection in potential donors of HCT/Ps

94973

Donor, HIV-1/2 Plus O Antibody Screen With Reflex to Differentiationa

 

Screen for HIV-1 and HIV-2 infection with reflex to confirmation/differentiation in potential donors of HCT/Ps

17379

Donor, HTLV-I/II Antibody Screen

 

Screen for human T-cell lymphotrophic virus I and II infection in potential donors of viable, leukocyte-rich cells and tissues

93309

Donor, Stem Cells Donor Panel

 

Screen for CMV, HBV, HCV, HIV, HTLV-I/II, syphilis, and WNV in potential stem cell donors

17389

Donor, Syphilis IgG Antibody

 

Screen for acute or chronic Treponema pallidum infection in potential donors of HCT/Ps

93308

Donor, Tissue Donor Panel

Includes donor, hepatitis B core total antibody; donor, hepatitis B surface antigen with reflex to confirm; donor, hepatitis C antibody (anti-HCV); donor, HIV/HCV/HBV NAT Procleix® with reflexes; donor, HIV-1/2 plus O antibody screen; donor, syphilis IgG antibody; donor, West Nile virus, NAT.

 

Screen for infectious diseases in potential tissue or blood donors

19412

Donor, West Nile Virus, NAT

 

Screen for WNV RNA in potential donors of HCT/Ps

CMV, cytomegalovirus; HBV, hepatitis B virus; HCV, hepatitis C virus; HCT/Ps, human cells, tissues, and cellular and tissue-based products; HIV, human immunodeficiency virus;; HTLV, human T-cell lymphotropic virus; NAT, nucleic acid amplification; TMA, transcription-mediated amplification; WNV, West Nile virus.
a Reflex tests are performed at an additional charge and are associated with an additional CPT® code(s).

 

Compatibility testing for transplant donors and recipients

A person's HLA type and antibody profile are important for assessing immunological compatibility between donor and recipient, as incompatibility can result in transplant rejection. HLA typing and antibody testing can help assess donor-recipient immunological risk. Testing options vary by HLA class and resolution (Table 2).

HLA proteins are grouped into 2 classes: class I includes A, B, and C antigens, and class II includes DR, DQ, and DP antigens. HLA A, B, and DR antigens are considered the most important in transplant survival; however, current Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) guidelines mandate molecular typing of all HLA loci, which may be performed at different levels of resolution depending on transplant center requirements.3 DNA-based typing at low resolution identifies the group of alleles that encode a particular HLA antigen. Intermediate-resolution typing is limited to particular allele groups expected in a population. High-resolution typing allows for a more precise determination of an allelic variant by identifying variants based on differences in antigen recognition site domains. HLA antibody tests identify preformed antibodies to donor HLA antigens in transplant recipients, which may develop from prior sensitization.10

Table 2. Donor–Recipient Compatibility Tests for Solid Organ and Bone Marrow Transplantation

Test code

Test name

HLA typing

92157

HLA A, B, C, Class I Typing, Intermediate Resolutiona

92076

HLA-A, B, C, DRB1 and DQ High Resolution

92078

HLA-A, B, C High Resolution

15484

HLA A, B, C Low Resolutiona

92158

HLA-A, B, Intermediate Resolutiona

15757

HLA A, B Low Resolutiona

92044

HLA A 02:01 Determinationa

10951

HLA A Low Resolutiona

17397

HLA A Typing, High Resolutiona

92746

HLA-B*15:02 Determination with Reflex to HLA-B High Resolutiona

10950

HLA B Low Resolutiona

17395

HLA C High Resolutiona

15463

HLA C Low Resolutiona

95730

HLA DPB1 Typing, High Resolutiona

19525

HLA DQA1 Low Resolutiona

10953

HLA DQB1 Low Resolutiona

17394

HLA DQB1 Typing, High Resolutiona

92159

HLA DRB1, DQB1, Intermediate Resolutiona

15485

HLA DRB1, DQB1 Low Resolutiona

97112

HLA DRB1,3,4,5,DQB1, Low Resolutiona

10952

HLA DRB1 Low Resolutiona

19526

HLA DRB3,4,5 Low Resolutiona

17393

HLA DRB1 Typing, High Resolutiona

95732

HLA DRB3,4,5 Typing, High Resolutiona

92160

HLA DRB1 Typing, Intermediate Resolutiona

92161

HLA DRB3,4,5 Typing, Intermediate Resolutiona

HLA antibody screening and identification

95731

HLA Antibody Identification, Class Ia

97111

HLA Antibody Identification, Class IIa

95735

HLA Antibody Screen, Class Ia

95736

HLA Antibody Screen, Class IIa

a This test was developed and its performance characteristics determined by this laboratory. It has not been cleared or approved by the US Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) as qualified to perform high-complexity clinical laboratory testing.

 

Post-transplant infectious disease testing

The risk of post-transplant infection varies with a patient’s state of immunosuppression and source of infectious exposures.11,12 Reactivation of donor-derived latent infections commonly occur within the first 4 weeks after transplantation, followed by a 1- to 12-month period during which patients who are immunosuppressed are at risk for opportunistic bacterial, fungal, or viral infections.11 After 1 year, patients are at highest risk for community-acquired infections.11 Certain types of infectious diseases are more common depending on epidemiological exposure, which may help guide diagnostic testing (Table 3).

Table 3. Post-transplant Tests for Infectious Diseases

Test code

Test name

39950

Specialized Transplant Services, Post-Transplanta

Donor-derived latent infections (<4 weeks)

18143

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Bloodb

18142

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Plasmab

18144

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Respiratoryb

18141

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Serumb

18060

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Plasmab

18059

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Serumb

18104

Post-Transplant, Hepatitis C Viral RNA, Real-Time PCR, Plasmab

18103

Post-Transplant, Hepatitis C Viral (HCV) RNA, Real-Time PCR, Serumb

18003

Post-Transplant, HIV-1 RNA, Real-Time PCR, Plasmab

Opportunistic (1 month to 12 months) and community acquired infections (>12 months)

18122

Post-Transplant, Adenovirus DNA, Real-Time PCR, Bloodb

18120

Post-Transplant, Adenovirus DNA, Real-Time PCR, Plasmab

18124

Post-Transplant, Adenovirus DNA, Real-Time PCR, Respiratoryb

18118

Post-Transplant, Adenovirus DNA, Real-Time PCR, Serumb

18126

Post-Transplant, Adenovirus DNA, Real-Time PCR, Urineb

18000

Post-Transplant, Aspergillus DNA, Qualitative Real-Time PCR, Bloodb

18001

Post-Transplant, Aspergillus DNA, Qualitative Real-Time PCR, Respiratoryb

18051

Post-Transplant, BK Virus DNA, Real-Time PCR, Bloodb

18050

Post-Transplant, BK Virus DNA, Real-Time PCR, Plasmab

18049

Post-Transplant, BK Virus DNA, Real-Time PCR, Serumb

18052

Post-Transplant, BK Virus DNA, Real-Time PCR, Urineb

18143

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Bloodb

18142

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Plasmab

18144

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Respiratoryb

18141

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Serumb

18090

Post-Transplant, Epstein-Barr Virus DNA, Real-Time PCR, Bloodb

18089

Post-Transplant, Epstein-Barr Virus DNA, Real-Time PCR, Plasmab

18088

Post-Transplant, Epstein-Barr Virus DNA, Real-Time PCR, Serumb

18060

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Plasmab

18059

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Serumb

18104

Post-Transplant, Hepatitis C Viral RNA, Real-Time PCR, Plasmab

18103

Post-Transplant, Hepatitis C Viral RNA, Real-Time PCR, Serumb

18022

Post-Transplant, Herpesvirus 6 DNA, Real-Time PCR, Bloodb

18020

Post-Transplant, Herpesvirus 6 DNA, Real-Time PCR, P0lasmab

18078

Post-Transplant, Herpesvirus 7 DNA, Real-Time PCR, Bloodb

18076

Post-Transplant, Herpesvirus 7 DNA, Real-Time PCR, Plasmab

18074

Post-Transplant, Herpesvirus 7 DNA, Real-Time PCR, Serumb

18132

Post-Transplant, Herpesvirus 8 DNA, Real-Time PCR, Bloodb

18130

Post-Transplant, Herpesvirus 8 DNA, Real-Time PCR, Plasmab

18128

Post-Transplant, Herpesvirus 8 DNA, Real-Time PCR, Serumb

18003

Post-Transplant, HIV-1 RNA, Real-Time PCR, Plasmab

18011

Post-Transplant, JC Virus DNA, Real-Time PCR, CSFb

18010

Post-Transplant, JC Virus DNA, Real-Time PCR, Plasmab

18009

Post-Transplant, JC Virus DNA, Real-Time PCR, Serumb

18070

Post-Transplant, Parvovirus B19 DNA, Real-Time PCR, Bloodb

18068

Post-Transplant, Parvovirus B19 DNA, Real-Time PCR, Plasmab

18066

Post-Transplant, Parvovirus B19 DNA, Real-Time PCR, Serumb

18146

Post-Transplant, Varicella-zoster Virus DNA, Real-Time PCR, Bloodb

18148

Post-Transplant, Varicella-zoster Virus DNA, Real-Time PCR, CSFb

18005

Post-Transplant, Pneumocystis jiroveci, Real-Time PCR, Respiratoryb

a Specialized transplant services include collection and shipping kits provided to the customer, direct shipping via FedEx, post-transplant-specific requisitions, and rapid turnaround (8-12 hours from laboratory receipt of sample). Test code 39950 designates special handling for these services; it is a single-use test code that may be applied to 1 or more tests in this section.
b This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

 

Other tests

Laboratory tests can also be used to monitor immunosuppressive and antifungal drug therapies (Table 4) and help optimize dose, avoid toxicity, and assure patient adherence.

Table 4. Post-transplant Testing for Therapeutic Drug Monitoring

Test code

Test name

Primary clinical use

Immunosuppressive therapy

10720

Cyclosporine A Panel (Trough, 1 Hour, 2 Hour Post)

Monitor immunosuppressive therapy to optimize dose, avoid toxicity, and help assure adherence to a treatment regimen

10719

Cyclosporine A Peak (2 Hour), Blood

8812

Cyclosporine A, Trough, Blood

15220

Cyclosporine A Trough, LC/MS/MS, Blooda

18883

Everolimus, LC/MS/MS, Blooda

10662

Mycophenolic Acida

36712

Sirolimus, LC/MS/MSa

70007

Tacrolimus, Highly Sensitive, LC/MS/MSa

91745

Thiopurine Metabolitesa

Antifungal therapy

94092

Itraconazolea

Monitor drug levels when unexpected toxicity is encountered; optimize dosage when drug interactions are suspected

94010

Posaconazolea

94096

Voriconazolea

94692

Voriconazole, CSFa

a This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

 

Laboratory tests can also be used during early follow-up to evaluate transplant viability, bone marrow cell engraftment, cell-mediated immune response complications, and the possibility of rejection or complications (Table 5).

Table 5. Post-transplant Testing for Early Follow-up

Test code

Test name

 

Primary clinical use

4944

Beta-2-Microglobulin, Random Urine

 

Evaluate transplant viability and anticipate rejection

38994

Beta-2-Microglobulin, Random Urine with Creatinine

852

Beta-2-Microglobulin, Serum

14619

FISH, X/Y, Post Opposite Sex Bone Marrow Transplant (BMT)

 

Monitor progression of bone marrow cell engraftment when bone marrow is from a donor of the opposite sex

15435

Immune Cell Function

 

Monitor cell-mediated immune response to optimize immunosuppressant therapy

34298

Interleukin-2 Receptor Alpha Chain (IL-2Ra/CD25), Solublea

 

Assess possibility of acute transplant rejection

34473

Interleukin-6 (IL-6), Seruma

 

Assess possibility of transplant-related complications after hematopoietic stem cell transplantation (SCT)

93917

Neopterin, Serumb

 

Monitor cell-mediated immunity

a This test was performed using a kit that has not been cleared or approved by the FDA. The analytical performance characteristics of this test have been determined by Quest Diagnostics. This test should not be used for diagnosis without confirmation by other medically established means.
b This test was performed using a kit that has not been cleared or approved by the FDA. The analytical performance characteristics of this test have been determined by Laboratory Corporation of America (LabCorp). This test should not be used for diagnosis without confirmation by other medically established means.

 

References

  1. Donor screening and testing. Centers for Disease Control and Prevention. Updated October 13, 2022. Accessed May 1, 2024. https://www.cdc.gov/transplant-safety/hcp/clinical-guidance/?CDC_AAref_Val=https://www.cdc.gov/transplantsafety/protecting-patient/screening-testing.html
  2. Lentine KL, Kasiske BL, Levey AS, et al. Summary of kidney disease. Transplantation. 2017;101(8):1783-1792. doi:10.1097/tp.0000000000001770
  3. Policies. The Organ Procurement and Transplantation Network. Updated May 29, 2024. Accessed June 1, 2024. https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_07
  4. Malinis M, Boucher HW. Screening of donor and candidate prior to solid organ transplantation—guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13548. doi:10.1111/ctr.13548
  5. Guidance for industry: eligibility determination for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps). US Food and Drug Administration. Updated May 2, 2024. Accessed May 13, 2024. https://www.fda.gov/media/73072/download
  6. Use of serological tests to reduce the risk of transmission of Trypanosoma cruzi infection in blood and blood components. Guidance for industry. US Food and Drug Administration. Updated May 16, 2019. Accessed May 13, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-serological-tests-reduce-risk-transmission-trypanosoma-cruzi-infection-blood-and-blood
  7. Freedman BI, Pastan SO, Israni AK, et al. APOL1 genotype and kidney transplantation outcomes from deceased African American donors. Transplantation. 2016;100(1):194-202. doi:10.1097/tp.0000000000000969
  8. Reeves-Daniel AM, DePalma JA, Bleyer AJ, et al. The APOL1 gene and allograft survival after kidney transplantation. Am J Transplant. 2011;11(5):1025-1030. doi:10.1111/j.1600-6143.2011.03513.x
  9. Complete list of donor screening assays for infectious agents and HIV diagnostic assays. US Food and Drug Administration. Updated April 12, 2024. Accessed May 13, 2024. https://www.fda.gov/vaccines-blood-biologics/complete-list-donor-screening-assays-infectious-agents-and-hiv-diagnostic-assays
  10. HLA testing for solid organ transplantation. American Association of Clinical Chemistry. Updated August 27, 2019. Accessed June 20, 2024. https://www.myadlm.org/Science-and-Research/Clinical-Chemistry/Clinical-Chemistry-Trainee-Council/Pearls-of-Laboratory-Medicine-in-English/2019/HLA-Testing-for-Solid-Organ-Transplantation
  11. Fishman JA. Infection in organ transplantation. Am J Transplant. 2017;17(4):856-879. doi:10.1111/ajt.14208
  12. Singh N, Limaye AP. Infections in solid-organ transplant recipients. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 2015:3440-3452. doi:10.1016/b978-1-4557-4801-3.00313-1
     

Content reviewed 08/2024

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This Test Guide discusses the use of laboratory tests that help match donors and recipients for solid organ and bone marrow transplantation, and also discusses tests that identify and monitor infectious disease in post-transplant recipients.

Solid Organ and Hematopoietic Stem Cell Transplantation: Laboratory Testing for Transplant Recipients

Test Guide

 

Solid Organ and Hematopoietic Stem Cell Transplantation

Laboratory Testing for Donors and Recipients

This Test Guide provides a description of tests available for transplant donors and recipients. Laboratory testing includes US Food and Drug Administration (FDA)-required testing of donors for certain infectious diseases,1 testing for genetic kidney diseases to evaluate donor candidates,2 guideline-indicated compatibility testing (human leukocyte antigen [HLA] typing and HLA antibody screening) for transplant donors and recipients,3 and post-transplant testing to monitor immunosuppressive and antifungal drug therapies and follow-up for infectious disease.

This Test Guide is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.

Donor testing

Laboratory testing can help avoid transmission of infectious disease through transplanted human cells, tissues, and cellular-based products (HCT/Ps) by identifying diseases or disease agents in potential donors with active or latent infections; immunosuppressive drugs used to prevent transplant rejection can reactivate latent infections.4

The FDA requires testing of all donors of HCT/Ps for infections including HIV-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum (syphilis); testing for West Nile virus (WNV) is required for living donors.1 Depending on HCT/P type, requirements may also include testing for human T-lymphotropic virus (HTLV), cytomegalovirus, Chlamydia trachomatis, Neisseria gonorrhea, and Trypanosoma cruzi, the parasite that causes Chagas disease (Table 1).5,6

For potential living kidney donors who self-report African ancestry, detection of any 2 APOL1 risk alleles (G1/G1, G2/G2, or G1/G2) indicates an increased risk for developing APOL1-associated chronic kidney disease. The risk of premature allograft loss associated with a high-risk genotype in a living donor is currently unknown, but a high-risk genotype in a deceased donor is associated with shorter allograft survival in transplant recipients.7,8

Quest Diagnostics offers a menu of pretransplant tests that includes APOL1 renal risk variant genotyping and donor screening panels for infectious diseases (Table 1); components of panels can be ordered separately. These panels, based on FDA guidelines for approved testing,5,9 include tests for HIV-1/2, HBV, HCV, CMV, T pallidum, and others.

Table 1. APOL1 Risk Variant and Infectious Disease Testing for Donors

Test code

Test name

 

Primary clinical use

Genotyping

1291

Apolipoprotein L1 (APOL1) Renal Risk Variant Genotyping

 

Assist evaluation of a potential donor for kidney transplantation

Infectious disease testing

91986

Donor, Chagas Screen

 

Screen for Trypanosoma cruzi infection in potential donors of HCT/Ps

17385

Donor, Chlamydia trachomatis/Neisseria gonorrhoeae, RNA, TMA

 

Screen for C trachomatis and N gonorrhoeae RNA in potential donors of reproductive HCT/Ps

17388

Donor, Cytomegalovirus Antibody, Total

 

Screen for CMV infection in potential donors of viable, leukocyte-rich cells or tissues

90557

Donor, Cytomegalovirus Antibody, Total With Reflex to (IgG, IgM)a

 

Screen with reflex to diagnostic testing for CMV infection in potential donors of viable, leukocyte-rich cells or tissues

19618

Donor, Cytomegalovirus Antibody Total With Reflex Non-donor CMV IgMa

17378

Donor, Hepatitis B Core Total Antibody

 

Screen for history of HBV infection in potential donors of HCT/Ps

17375

Donor, Hepatitis B Surface Antigen With Reflex to Confirma

 

Screen and confirmation for acute or chronic HBV infection in potential donors of HCT/Ps

93305

Donor, Hepatitis C Antibody (Anti-HCV)

 

Screen for acute or chronic HCV infection in potential donors of HCT/Ps

19854

Donor, HIV/HCV/HBV NAT Procleix® With Reflexesa

 

Screen for HIV-1 RNA, HIV-2 RNA, HCV RNA, and HBV DNA in potential donors of HCT/Ps

17380

Donor, HIV-1/2 Plus O Antibody Screen

 

Screen for HIV-1 and HIV-2 infection in potential donors of HCT/Ps

94973

Donor, HIV-1/2 Plus O Antibody Screen With Reflex to Differentiationa

 

Screen for HIV-1 and HIV-2 infection with reflex to confirmation/differentiation in potential donors of HCT/Ps

17379

Donor, HTLV-I/II Antibody Screen

 

Screen for human T-cell lymphotrophic virus I and II infection in potential donors of viable, leukocyte-rich cells and tissues

93309

Donor, Stem Cells Donor Panel

 

Screen for CMV, HBV, HCV, HIV, HTLV-I/II, syphilis, and WNV in potential stem cell donors

17389

Donor, Syphilis IgG Antibody

 

Screen for acute or chronic Treponema pallidum infection in potential donors of HCT/Ps

93308

Donor, Tissue Donor Panel

Includes donor, hepatitis B core total antibody; donor, hepatitis B surface antigen with reflex to confirm; donor, hepatitis C antibody (anti-HCV); donor, HIV/HCV/HBV NAT Procleix® with reflexes; donor, HIV-1/2 plus O antibody screen; donor, syphilis IgG antibody; donor, West Nile virus, NAT.

 

Screen for infectious diseases in potential tissue or blood donors

19412

Donor, West Nile Virus, NAT

 

Screen for WNV RNA in potential donors of HCT/Ps

CMV, cytomegalovirus; HBV, hepatitis B virus; HCV, hepatitis C virus; HCT/Ps, human cells, tissues, and cellular and tissue-based products; HIV, human immunodeficiency virus;; HTLV, human T-cell lymphotropic virus; NAT, nucleic acid amplification; TMA, transcription-mediated amplification; WNV, West Nile virus.
a Reflex tests are performed at an additional charge and are associated with an additional CPT® code(s).

 

Compatibility testing for transplant donors and recipients

A person's HLA type and antibody profile are important for assessing immunological compatibility between donor and recipient, as incompatibility can result in transplant rejection. HLA typing and antibody testing can help assess donor-recipient immunological risk. Testing options vary by HLA class and resolution (Table 2).

HLA proteins are grouped into 2 classes: class I includes A, B, and C antigens, and class II includes DR, DQ, and DP antigens. HLA A, B, and DR antigens are considered the most important in transplant survival; however, current Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) guidelines mandate molecular typing of all HLA loci, which may be performed at different levels of resolution depending on transplant center requirements.3 DNA-based typing at low resolution identifies the group of alleles that encode a particular HLA antigen. Intermediate-resolution typing is limited to particular allele groups expected in a population. High-resolution typing allows for a more precise determination of an allelic variant by identifying variants based on differences in antigen recognition site domains. HLA antibody tests identify preformed antibodies to donor HLA antigens in transplant recipients, which may develop from prior sensitization.10

Table 2. Donor–Recipient Compatibility Tests for Solid Organ and Bone Marrow Transplantation

Test code

Test name

HLA typing

92157

HLA A, B, C, Class I Typing, Intermediate Resolutiona

92076

HLA-A, B, C, DRB1 and DQ High Resolution

92078

HLA-A, B, C High Resolution

15484

HLA A, B, C Low Resolutiona

92158

HLA-A, B, Intermediate Resolutiona

15757

HLA A, B Low Resolutiona

92044

HLA A 02:01 Determinationa

10951

HLA A Low Resolutiona

17397

HLA A Typing, High Resolutiona

92746

HLA-B*15:02 Determination with Reflex to HLA-B High Resolutiona

10950

HLA B Low Resolutiona

17395

HLA C High Resolutiona

15463

HLA C Low Resolutiona

95730

HLA DPB1 Typing, High Resolutiona

19525

HLA DQA1 Low Resolutiona

10953

HLA DQB1 Low Resolutiona

17394

HLA DQB1 Typing, High Resolutiona

92159

HLA DRB1, DQB1, Intermediate Resolutiona

15485

HLA DRB1, DQB1 Low Resolutiona

97112

HLA DRB1,3,4,5,DQB1, Low Resolutiona

10952

HLA DRB1 Low Resolutiona

19526

HLA DRB3,4,5 Low Resolutiona

17393

HLA DRB1 Typing, High Resolutiona

95732

HLA DRB3,4,5 Typing, High Resolutiona

92160

HLA DRB1 Typing, Intermediate Resolutiona

92161

HLA DRB3,4,5 Typing, Intermediate Resolutiona

HLA antibody screening and identification

95731

HLA Antibody Identification, Class Ia

97111

HLA Antibody Identification, Class IIa

95735

HLA Antibody Screen, Class Ia

95736

HLA Antibody Screen, Class IIa

a This test was developed and its performance characteristics determined by this laboratory. It has not been cleared or approved by the US Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) as qualified to perform high-complexity clinical laboratory testing.

 

Post-transplant infectious disease testing

The risk of post-transplant infection varies with a patient’s state of immunosuppression and source of infectious exposures.11,12 Reactivation of donor-derived latent infections commonly occur within the first 4 weeks after transplantation, followed by a 1- to 12-month period during which patients who are immunosuppressed are at risk for opportunistic bacterial, fungal, or viral infections.11 After 1 year, patients are at highest risk for community-acquired infections.11 Certain types of infectious diseases are more common depending on epidemiological exposure, which may help guide diagnostic testing (Table 3).

Table 3. Post-transplant Tests for Infectious Diseases

Test code

Test name

39950

Specialized Transplant Services, Post-Transplanta

Donor-derived latent infections (<4 weeks)

18143

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Bloodb

18142

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Plasmab

18144

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Respiratoryb

18141

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Serumb

18060

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Plasmab

18059

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Serumb

18104

Post-Transplant, Hepatitis C Viral RNA, Real-Time PCR, Plasmab

18103

Post-Transplant, Hepatitis C Viral (HCV) RNA, Real-Time PCR, Serumb

18003

Post-Transplant, HIV-1 RNA, Real-Time PCR, Plasmab

Opportunistic (1 month to 12 months) and community acquired infections (>12 months)

18122

Post-Transplant, Adenovirus DNA, Real-Time PCR, Bloodb

18120

Post-Transplant, Adenovirus DNA, Real-Time PCR, Plasmab

18124

Post-Transplant, Adenovirus DNA, Real-Time PCR, Respiratoryb

18118

Post-Transplant, Adenovirus DNA, Real-Time PCR, Serumb

18126

Post-Transplant, Adenovirus DNA, Real-Time PCR, Urineb

18000

Post-Transplant, Aspergillus DNA, Qualitative Real-Time PCR, Bloodb

18001

Post-Transplant, Aspergillus DNA, Qualitative Real-Time PCR, Respiratoryb

18051

Post-Transplant, BK Virus DNA, Real-Time PCR, Bloodb

18050

Post-Transplant, BK Virus DNA, Real-Time PCR, Plasmab

18049

Post-Transplant, BK Virus DNA, Real-Time PCR, Serumb

18052

Post-Transplant, BK Virus DNA, Real-Time PCR, Urineb

18143

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Bloodb

18142

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Plasmab

18144

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Respiratoryb

18141

Post-Transplant, Cytomegalovirus DNA, Real-Time PCR, Serumb

18090

Post-Transplant, Epstein-Barr Virus DNA, Real-Time PCR, Bloodb

18089

Post-Transplant, Epstein-Barr Virus DNA, Real-Time PCR, Plasmab

18088

Post-Transplant, Epstein-Barr Virus DNA, Real-Time PCR, Serumb

18060

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Plasmab

18059

Post-Transplant, Hepatitis B Virus DNA, Real-Time PCR, Serumb

18104

Post-Transplant, Hepatitis C Viral RNA, Real-Time PCR, Plasmab

18103

Post-Transplant, Hepatitis C Viral RNA, Real-Time PCR, Serumb

18022

Post-Transplant, Herpesvirus 6 DNA, Real-Time PCR, Bloodb

18020

Post-Transplant, Herpesvirus 6 DNA, Real-Time PCR, P0lasmab

18078

Post-Transplant, Herpesvirus 7 DNA, Real-Time PCR, Bloodb

18076

Post-Transplant, Herpesvirus 7 DNA, Real-Time PCR, Plasmab

18074

Post-Transplant, Herpesvirus 7 DNA, Real-Time PCR, Serumb

18132

Post-Transplant, Herpesvirus 8 DNA, Real-Time PCR, Bloodb

18130

Post-Transplant, Herpesvirus 8 DNA, Real-Time PCR, Plasmab

18128

Post-Transplant, Herpesvirus 8 DNA, Real-Time PCR, Serumb

18003

Post-Transplant, HIV-1 RNA, Real-Time PCR, Plasmab

18011

Post-Transplant, JC Virus DNA, Real-Time PCR, CSFb

18010

Post-Transplant, JC Virus DNA, Real-Time PCR, Plasmab

18009

Post-Transplant, JC Virus DNA, Real-Time PCR, Serumb

18070

Post-Transplant, Parvovirus B19 DNA, Real-Time PCR, Bloodb

18068

Post-Transplant, Parvovirus B19 DNA, Real-Time PCR, Plasmab

18066

Post-Transplant, Parvovirus B19 DNA, Real-Time PCR, Serumb

18146

Post-Transplant, Varicella-zoster Virus DNA, Real-Time PCR, Bloodb

18148

Post-Transplant, Varicella-zoster Virus DNA, Real-Time PCR, CSFb

18005

Post-Transplant, Pneumocystis jiroveci, Real-Time PCR, Respiratoryb

a Specialized transplant services include collection and shipping kits provided to the customer, direct shipping via FedEx, post-transplant-specific requisitions, and rapid turnaround (8-12 hours from laboratory receipt of sample). Test code 39950 designates special handling for these services; it is a single-use test code that may be applied to 1 or more tests in this section.
b This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

 

Other tests

Laboratory tests can also be used to monitor immunosuppressive and antifungal drug therapies (Table 4) and help optimize dose, avoid toxicity, and assure patient adherence.

Table 4. Post-transplant Testing for Therapeutic Drug Monitoring

Test code

Test name

Primary clinical use

Immunosuppressive therapy

10720

Cyclosporine A Panel (Trough, 1 Hour, 2 Hour Post)

Monitor immunosuppressive therapy to optimize dose, avoid toxicity, and help assure adherence to a treatment regimen

10719

Cyclosporine A Peak (2 Hour), Blood

8812

Cyclosporine A, Trough, Blood

15220

Cyclosporine A Trough, LC/MS/MS, Blooda

18883

Everolimus, LC/MS/MS, Blooda

10662

Mycophenolic Acida

36712

Sirolimus, LC/MS/MSa

70007

Tacrolimus, Highly Sensitive, LC/MS/MSa

91745

Thiopurine Metabolitesa

Antifungal therapy

94092

Itraconazolea

Monitor drug levels when unexpected toxicity is encountered; optimize dosage when drug interactions are suspected

94010

Posaconazolea

94096

Voriconazolea

94692

Voriconazole, CSFa

a This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

 

Laboratory tests can also be used during early follow-up to evaluate transplant viability, bone marrow cell engraftment, cell-mediated immune response complications, and the possibility of rejection or complications (Table 5).

Table 5. Post-transplant Testing for Early Follow-up

Test code

Test name

 

Primary clinical use

4944

Beta-2-Microglobulin, Random Urine

 

Evaluate transplant viability and anticipate rejection

38994

Beta-2-Microglobulin, Random Urine with Creatinine

852

Beta-2-Microglobulin, Serum

14619

FISH, X/Y, Post Opposite Sex Bone Marrow Transplant (BMT)

 

Monitor progression of bone marrow cell engraftment when bone marrow is from a donor of the opposite sex

15435

Immune Cell Function

 

Monitor cell-mediated immune response to optimize immunosuppressant therapy

34298

Interleukin-2 Receptor Alpha Chain (IL-2Ra/CD25), Solublea

 

Assess possibility of acute transplant rejection

34473

Interleukin-6 (IL-6), Seruma

 

Assess possibility of transplant-related complications after hematopoietic stem cell transplantation (SCT)

93917

Neopterin, Serumb

 

Monitor cell-mediated immunity

a This test was performed using a kit that has not been cleared or approved by the FDA. The analytical performance characteristics of this test have been determined by Quest Diagnostics. This test should not be used for diagnosis without confirmation by other medically established means.
b This test was performed using a kit that has not been cleared or approved by the FDA. The analytical performance characteristics of this test have been determined by Laboratory Corporation of America (LabCorp). This test should not be used for diagnosis without confirmation by other medically established means.

 

References

  1. Donor screening and testing. Centers for Disease Control and Prevention. Updated October 13, 2022. Accessed May 1, 2024. https://www.cdc.gov/transplant-safety/hcp/clinical-guidance/?CDC_AAref_Val=https://www.cdc.gov/transplantsafety/protecting-patient/screening-testing.html
  2. Lentine KL, Kasiske BL, Levey AS, et al. Summary of kidney disease. Transplantation. 2017;101(8):1783-1792. doi:10.1097/tp.0000000000001770
  3. Policies. The Organ Procurement and Transplantation Network. Updated May 29, 2024. Accessed June 1, 2024. https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_07
  4. Malinis M, Boucher HW. Screening of donor and candidate prior to solid organ transplantation—guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13548. doi:10.1111/ctr.13548
  5. Guidance for industry: eligibility determination for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps). US Food and Drug Administration. Updated May 2, 2024. Accessed May 13, 2024. https://www.fda.gov/media/73072/download
  6. Use of serological tests to reduce the risk of transmission of Trypanosoma cruzi infection in blood and blood components. Guidance for industry. US Food and Drug Administration. Updated May 16, 2019. Accessed May 13, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-serological-tests-reduce-risk-transmission-trypanosoma-cruzi-infection-blood-and-blood
  7. Freedman BI, Pastan SO, Israni AK, et al. APOL1 genotype and kidney transplantation outcomes from deceased African American donors. Transplantation. 2016;100(1):194-202. doi:10.1097/tp.0000000000000969
  8. Reeves-Daniel AM, DePalma JA, Bleyer AJ, et al. The APOL1 gene and allograft survival after kidney transplantation. Am J Transplant. 2011;11(5):1025-1030. doi:10.1111/j.1600-6143.2011.03513.x
  9. Complete list of donor screening assays for infectious agents and HIV diagnostic assays. US Food and Drug Administration. Updated April 12, 2024. Accessed May 13, 2024. https://www.fda.gov/vaccines-blood-biologics/complete-list-donor-screening-assays-infectious-agents-and-hiv-diagnostic-assays
  10. HLA testing for solid organ transplantation. American Association of Clinical Chemistry. Updated August 27, 2019. Accessed June 20, 2024. https://www.myadlm.org/Science-and-Research/Clinical-Chemistry/Clinical-Chemistry-Trainee-Council/Pearls-of-Laboratory-Medicine-in-English/2019/HLA-Testing-for-Solid-Organ-Transplantation
  11. Fishman JA. Infection in organ transplantation. Am J Transplant. 2017;17(4):856-879. doi:10.1111/ajt.14208
  12. Singh N, Limaye AP. Infections in solid-organ transplant recipients. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 2015:3440-3452. doi:10.1016/b978-1-4557-4801-3.00313-1
     

Content reviewed 08/2024

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