We thank Dr Foon for his letter, which allows us to clarify a few important points.
The first question relates to the definition of (complete) response by the examination of peripheral blood counts and marrow. This point has been addressed by the final version of the manuscript1 :
Despite the advent of techniques for evaluation of minimal residual disease (MRD), we retained the established definition of complete response (CR)2 to allow for comparison between the results of older trials with those completed after publication of the 2008 guidelines (see sections 5.1.1 [peripheral blood lymphocytes] and 5.1.6 [marrow]).
In the same sections, we recommended that clinical trials aimed at maximizing the CR rate should assess for MRD by flow cytometry (described in section 5.9) or by immunohistochemistry (IHC).
Moreover, in section 5.1.6 we recommended that lymphoid nodules found in the response-assessment marrow biopsy should be recorded as “nodular PR” and that IHC be performed to determine whether these nodules are composed primarily of T cells or lymphocytes other than CLL cells or of CLL cells.
The second question relates to the recommended use of computed tomography (CT) scans in clinical trials that we provided in section 5.1.2 and 5.2.2:
We stated in section 3.5.2.2 that CT scans generally are not required for the initial evaluation or follow-up. However, we recommended that CT scans be used in clinical trials intended to maximize complete remission, one at the start of therapy and the other at first restaging after therapy if previously abnormal.
In Table 3 of our article we point out that assessment of a PR may not require a CT scan at restaging if the residual disease can be detected by other methods (eg, blood counts or palpation).
With regard to the differences in the minimal residual disease criteria and for a CR between the published and online versions, we wish to emphasize that due to a series of unfortunate events, the version published in paper form in June 2008 was not approved by the authors. Only the final version of the manuscript published in December 2008 was approved by the authors of the paper.
Authorship
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Michael Hallek, MD, Director, Klinik I für Innere Medizin, Universität zu Köln, Joseph-Stelzmann Str 9, 50924 Köln, Germany; e-mail: michael.hallek@uni-koeln.de.
