VARIABLE NUMBERS OF BCR-ABL TRANSCRIPTS PERSIST IN CML PATIENTS WHO ACHIEVE COMPLETE CYTOGENETIC REMISSION WITH INTERFERON-ALPHA

A substantial minority of patients with chronic myeloid leukaemia (CML ) achieve a complete response to treatment with interferon-alpha (IFN- alpha), defined as the disappearance of Philadelphia chromosome positi ve metaphases or, for patients who are Philadelphia chromosome negativ e but BCR-ABL positive, the disappearance of the leukaemic clone as as sayed by Southern blot. We have measured the levels of BCR-ABL transcr ipts in 20 such patients by quantitative PCR. Results were standardize d for both quality and quantity of cDNA by quantification of ABL as an internal control. All 20 patients had evidence of residual disease; t he median number of transcripts was 750/mu g RNA (range 10-22 000) and the median BCR-ABL/ABL ratio was 0.17% (range 0.0008-3.6%). Our findi ngs show that CML has not been eradicated in any patient and that the quantity of residual disease in complete responders may vary by as muc h as four orders of magnitude.