Dear Sir, By describing the long-time persistence of major and complete molecular responses in two patients with chronic myeloid leukaemia (CML) after cessation of interferon-α therapy, we would like to take part in the debate regarding discontinuation of treatment in CML patients. The first case, a 64-year old man, was diagnosed with CML in September 1990. Treatment was discontinued, at the patient’s request, in June 2002 during a major molecular remission. The second case, a 34-year old male was diagnosed with CML in March 1997. Interferon-α was stopped in December 2005 due to an acute myocardial infarction. The patient had been in complete molecular remission since September 1999. Following discontinuation of interferon-α, both patients were evaluated twice a year by real time quantitative and/or nested polymerase chain reaction (PCR) analysis of BCR-ABL mRNA from peripheral blood. To date, the patients are in persistent major molecular remission (BCR-ABL:ABL-ABL ratio: 0.0103) and complete molecular remission at 107 and 65 months, respectively, since treatment cessation. In the past, allogeneic haemopoietic stem-cell transplantation (HSCT) was indicated to be the only cure for CML because disease recurrence was not observed in most transplanted patients who achieved a complete molecular response1. However, imatinib, a tyrosine-kinase inhibitor, currently represents the standard of care for patients with newly diagnosed CML. It produces a major molecular response in a large proportion of patients and, over time, can also induce a complete molecular response2. Unfortunately, disease recurrence is reported early after treatment cessation in about 60% of patients in complete molecular remission, although the majority of patients remain responsive to re-treatment after recurrence. Conversely, about 40% of patients maintain a complete molecular response after withdrawal of tyrosine kinase inhibitor treatment. It is interesting to note that previous treatment with interferon-α does not increase the percentage of patients with persistent complete molecular remission3. In our opinion, it is reasonable to consider that in CML the long-time persistence of molecular response after therapy cessation does not depend on the type of treatment adopted, i.e. interferon-α, HSCT, or tyrosine-kinase inhibitors, with the last being by far the most effective therapy. However, if CML is an incurable disease, it is difficult to explain why it does not recur in about 40% of patients after withdrawal of tyrosine-kinase inhibitors; contrariwise, if CML is a curable disease, there is the same difficulty in explaining why it does recur in about 60% of patients in complete molecular remission. As a consequence, we may consider that assessment of BCR-ABL transcripts by PCR analysis is not a fully reliable method for evaluating disease status. Along with clinical features such as low Sokal score, male sex and duration of imatinib treatment, predictive of maintaining complete molecular response after suspension of imatinib, a more sensitive and standardised PCR technology should be designed in order to identify those patients in whom treatment could be withdrawn. In addition, considering that we did not observe progression of disease after discontinuation of interferon-α, even in the patient in major molecular remission, and that other authors did not observe disease recurrence in patients in complete cytogenetic remission4 (not necessarily in complete molecular remission), it is reasonable to hypothesise that other biological markers should be identified to assess the real status of disease5. In conclusion, in spite of the fact that discontinuation of treatment is not warranted outside the context of clinical studies, our observation adds support to the concept that CML may be cured without HSCT, at least in some patients.
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