Sustained Complete Molecular Remissions After Treatment With Imatinib-Mesylate in Patients With Failure After Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia: Results of a Prospective Phase II Open-Label Multicenter Study

American Society of Clinical Oncology (ASCO) - Tập 23 Số 30 - Trang 7583-7593 - 2005
Georg Heß1, Donald Bunjes1, W. Siegert1, Rainer Schwerdtfeger1, Georg Ledderose1, Barbara Waßmann1, Guido Kobbe1, Martin Bornhäuser1, Andreas Hochhaus1, Andrew J. Ullmann1, Thomas Kindler1, Ulrike Haus1, Harald Gschaidmeier1, Christoph Huber1, Thomas Fischer1
1From the III. Med. Klinik, Johannes Gutenberg-University, Mainz; University of Ulm, II. Med. Klinik, Charité; Humboldt University, Berlin; Deutsche Klinik für Diagnostik Wiesbaden, University of Munich, University of Frankfurt, University of Düsseldorf, University of Dresden, University of Heidelberg at Mannheim, Novartis AG, Nürnberg, Germany

Tóm tắt

Purpose In 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 Methods As 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. Conclusion The 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.

Từ khóa


Tài liệu tham khảo

Nowell PC, Hungerford DA: A minute chromosome in chronic granulocytic leukemia. Science 132:1497,1960,

10.1038/243290a0

10.1038/306239a0

10.1182/blood.V96.10.3343

10.1056/NEJM199804023381405

10.1182/blood.V98.7.2039

10.1182/blood.V73.6.1720.1720

10.1182/blood.V75.3.555.555

10.1182/blood.V95.8.2659

Collins RH, Roggers ZR, Bennett M, et al: Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: Apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. Bone Marrow Transplant 10:391,1992-395,

10.1016/S0301-472X(99)00096-X

10.1182/blood.V86.5.2041.bloodjournal8652041

10.1200/JCO.1997.15.2.433

10.1182/blood.V86.4.1261.bloodjournal8641261

10.1182/blood.V95.1.67

10.1182/blood.V100.2.397

10.1038/nm0596-561

10.1006/bcmd.1997.0155

10.1093/jnci/91.2.163

10.1182/blood.V99.6.1928

10.1056/NEJMoa011573

10.1182/blood.V99.10.3530

10.1056/NEJMoa022457

10.1182/blood.V100.5.1590.h81702001590_1590_1595

10.1038/sj.leu.2403068

10.1158/1078-0432.CCR-03-0580

10.1038/sj.leu.2403157

10.1038/sj.leu.2401566

Weisser A; La Rosée P, Burmeister T, et al: Sensitivity, quality and comparability of Bcr-Abl quantification by RT-PCR: Results of an interlaboratory analysis. Blood 98,2001, (abstr 1352)

10.1182/blood-2004-03-1134

10.1016/S0165-4608(99)00133-8

10.1038/sj.leu.2402680

10.1046/j.1365-2141.2002.03705.x

10.1038/sj.leu.2403033

10.1038/sj.leu.2403135

10.1056/NEJM200104053441401

10.1056/NEJMoa030513

10.1182/blood-2003-11-3800

10.1126/science.1099480

10.1182/blood.V104.1.10.10

Thông tin
Thông tin xuất bản

American Society of Clinical Oncology (ASCO)

Tập 23 Số 30

7583-7593

Thông tin tác giả