Monitoring of adult B-cell lineage acute lymphoblastic leukemia: validation of a simple method for detecting immunoglobulin heavy chain gene clonality.
Most approaches to demonstrating immunoglobulin heavy chain gene rearrangements are relatively laborious for routine follow-up of acute lymphoblastic leukemia (ALL). Here the use of a simple polymerase chain reaction (PCR) approach to monitor ALL disease activity has been validated. In the dilution experiments the method revealed a detection sensitivity 0.5% clonal cells in a background of 99.5% normal cells. To validate the immunoglobulin heavy chain gene PCH (IgH-PCR) in practice, we monitored the disease activity of 26 adult ALL patients showing a B-cell lineage component in immunophenotyping at the diagnosis of the disease. In 18 of those 26 patients, an IgH-PCR product could be demonstrated in the samples taken either at diagnosis or in relapse. These 18 patients were followed with a total of 158 consecutive samples by IgH-PCR. The mean follow-up time for the IgH-PCR-positive patients was 13.6 months (range 4 to 26 months). Eleven of these patients underwent altogether 18 relapses. In nine patients (81.8%), ten relapses (55.6%) could be predicted using the IgH-PCR approach. The mean time of IgH-PCR clonality detection, preceding a cytologic relapse, was 9.1 weeks (range 1.0 to 30.7 weeks). It seems that in three patients the predictive value of the IgH-PCR was remarkable, showing a repetitive positivity in spite of a cytologic remission, even one year prior to the relapse. We find that IgH-PCR provides a straightforward additional tool for monitoring B-cell lineage ALL. Due to the straightforward technical performance the method has low running costs and it is thus suitable for a routine service laboratory. Even if a negative finding in IgH-PCR does not rule out a forthcoming relapse in the patient, a positive finding is a definitive warning signal. All of the patients that showed an IgH-PCR clonality in the follow-up samples relapsed sooner or later.
Department of Clinical Chemistry, University of Helsinki, Finland.
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Salo
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Pakkala
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Jansson
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Helminen
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Palotie
D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests