Response criteria with fludarabine therapy in chronic lymphocytic leukemia.

I read with great interest a report by OBrien et all in a recent issue of Blood in which results on a large series of chronic lymphocytic leukemia (CLL) patients treated at the M.D. Anderson Cancer Center with a combination of fludarabine and prednisone have been presented. As stated in the report, although this combination “has significant activity in CLL, the response rates were no higher than seen with fludarabine used alone.” However, the complete remission (CR) rate reported in this article is 63% among previously untreated patients. I believe that, in this evaluation, the investigators have included among CRs patients achieving “nodular partial remissions (PRs)” as defined by Keating et al.2 Keating et aI2 in reporting their results on 33 previously untreated CLL patients showed 33% CRs, and this figure increased to 72% if an additional 39% nodular PRs were included among CRs. The clinical behavior of patients achieving nodular PR was later shown to be closer to that of PRrather than CR-achieving patients.’ Even 33% is a major improvement2 in achieving CR in CLL and this, in itself, promises to result in an improvement in the natural history of this disease-which we have been unable to do during the past 3 decades. The results with fludarabine in previously untreated CLL patients obtained at a single institution ( M D . Anderson Cancer Center) were considered to be so exciting(33% CRs) that 3 yearsago, Cancer And Leukemia Group B (CALGB) initiated a major trial to test if these results can be reproduced in a multi-institutional setting. Other National Cancer Institute (NC1)-supported large groups have since joined this CALGB study, thus making it an Intergroup trial with the Southwest Oncology Group, National Cancer InstituteCanada, Clinical Trials Group, and Eastern Cooperative Oncology Group also participating. In this Intergroup study, patients are randomly assigned one of the following three therapeutic arms: ( l ) fludarabine alone, (2) chlorambucil alone, and (3) a combination of fludarabine and chlorambucil. It is anticipated that new patient accrual on this study will end within a year. It would be very helpful if OBrien et a1 also provided us with e details of how many of their CRs actually had nodular PRs and whether the duration of remission and overall survival of nodular PR-achieving patients were closer to those of PRs or of CRs. There are two typographical and editorial errors in the paper by OBrien et al,’ which ought to be corrected: In the abstract “64% and 46%” have been given at two places, it should be replaced by “36% and 19%” for previously treated Rai 111-IV disease. At the top of page 1697, in platelets less than 100 X IO3, “100 X” is missing.