• Georg Hess, Donald Bunjes, Wolfgang Siegert, Rainer Schwerdtfeger, Georg Ledderose, Barbara Wassmann, Guido Kobbe, Martin Bornhäuser, Andreas Hochhaus, Andrew J Ullmann, Thomas Kindler, Ulrike Haus, Harald Gschaidmeier, Christoph Huber, and Thomas Fischer.
• III. Med. Klinik, Johannes Gutenberg-University, Mainz; University of Ulm, II. Med. Klinik, Charité, Germany.
• J. Clin. Oncol. 2005 Oct 20; 23 (30): 7583-93.

PurposeIn the era of molecular therapy of chronic myelogenous leukemia (CML) applying BCR-ABL tyrosine kinase inhibitors, the usefulness of molecular end points, in particular, quantitative polymerase chain reaction (PCR) for BCR-ABL in monitoring responses has been broadly accepted. Therefore, we have designed a prospective phase II trial in CML, which, for the first time, evaluated the feasibility and safety of molecular end points as surrogate markers to guide through a stratified treatment algorithm within a multicenter trial.Patients And MethodsAs a clinical model, we adopted minimal residual disease (MRD) found in relapse after allogeneic stem cell transplantation (SCT) in CML. Forty-four patients were enrolled and received the BCR-ABL tyrosine kinase inhibitor imatinib (IM) at a starting dose of 400 mg/d. The quality of molecular responses achieved then decided on discontinuation of IM or dose escalation up to 800 mg/d, and finally, on application of donor lymphocyte infusions. Results Seventy percent of patients achieved a complete molecular response (CMR), defined as nested PCR-negativity for BCR-ABL in three consecutive samples. Interestingly, in four out of 10 patients who discontinued IM, CMR was durable even after cessation of IM with a median follow-up of 494 days. This suggests the possibility of long-term tumor control in a subset of patients.ConclusionThe treatment strategy showed that IM treatment was well-tolerated and highly efficacious in MRD after allogeneic SCT. Moreover, this study demonstrated that evaluation of a molecular end point within a multicenter trial can be a safe and effective tool for clinical decision making.

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