Authors' objectives:

The Australian Health Technology Advisory Committee (AHTAC) completed a review of nucleic acid amplification (NAA) technology in 1997. The use of polymerase chain reaction (PCR) was recommended for diagnosis and monitoring of chronic myeloid leukaemia (CML) in that report. MSAC was approached by the Pathology Services Table Committee (PSTC) to review the use of NAA in CML as well as other indications considered in the 1997 report. The NAA supporting committee developed the following questions for CML:

Does the evidence support the use of PCR in the diagnosis and monitoring of CML? Specifically: - Does BCR-ABL detection by PCR increase the proportion of patients who are recognised to have a specific disease entity (CML) that defines a specific therapeutic strategy? - Does repeated qualitative or quantitative PCR testing in CML influence management?

Detection of other cytogenetic abnormalities have important prognostic and therapeutic implications, so PCR testing is a supplementary rather than a replacement test.

Authors' results and conclusions: Diagnostic accuracy in CML monitoring using qualitative PCR The PCR was evaluated for its ability to predict cytogenetic and haematological relapse in the monitoring studies. Twenty-five studies were eligible for this section of the review. All but one were conducted solely in the post-transplant setting. All 25 studies were case series. There was variation in the study populations, including time since transplant. The pooled diagnostic odds ratio (DOR) from these studies, based on validity estimates more than six months post-transplant, was 25 (95% CI 14, 45) indicating a refinement in assessing the likelihood of subsequent cytogenetic or haematological relapse as a result of using the PCR. For instance, a DOR of 25 is consistent with a sensitivity of 85 per cent and specificity of 81 per cent. Biases in the individual studies would act in both directions on the validity estimates. The DOR would be overestimated by lack of blinding, and potentially by verification bias, but underestimated due to short follow up in some studies. Diagnostic accuracy in CML monitoring using quantitative PCR As with qualitative PCR, quantitative PCR was evaluated for its ability to predict cytogenetic and haematological relapse. Sixteen studies were eligible for the review. Ten were conducted solely in the posttransplant setting, four had mixed study populations and two consisted of study populations treated with chemotherapy alone. Ten allowed an assessment of sensitivity and specificity of PCR. All were case series. Most studies classified patients as PCR positive on the basis of single high levels or increasing levels on sequential samples. There was variation in the study populations, including time since transplant. The median sensitivity was 100 per cent (range 70-100) and median specificity was 83 per cent (range 62-100). Specificity is likely to be underestimated due to incomplete follow up for cytogenetic and haematological relapse. The pooled DOR was estimated for the three highest quality studies as nine (95% CI 5, 15). A DOR of nine is consistent with a sensitivity and specificity of 75 per cent.

Authors' recommendations: MSAC recommended that on the strength of evidence pertaining to safety, effectiveness and cost effectiveness of polymerase chain reaction (PCR) testing in the diagnosis and monitoring of BCR-ABL gene rearrangement in patients with chronic myeloid leukaemia (CML), public funding should be supported for this procedure.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.msac.gov.au/pdfs/reports/msacref9ai.pdf

Year Published: 2003

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Australia

Organisation Name: Medical Services Advisory Committee

Contact Address: MSAC (MDP 107), GPO Box 9848, Canberra, ACT 2601, Australia. Tel: +61 2 6289 6811; Fax: +61 2 6289 8799.

Contact Name: msac.secretariat@health.gov.au

Contact Email: msac.secretariat@health.gov.au

Copyright: Medicare Services Advisory Committee (MSAC)