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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.
J Clin Oncol 2005; 23(30):7583-93JC

Abstract

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.

Authors+Show Affiliations

III. Med. Klinik, Johannes Gutenberg-University, Mainz; University of Ulm, II. Med. Klinik, Charité, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Journal Article
Multicenter Study

Language

eng

PubMed ID

16234522

Citation

Hess, Georg, et al. "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." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 23, no. 30, 2005, pp. 7583-93.
Hess G, Bunjes D, Siegert W, et al. 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. J Clin Oncol. 2005;23(30):7583-93.
Hess, G., Bunjes, D., Siegert, W., Schwerdtfeger, R., Ledderose, G., Wassmann, B., ... Fischer, T. (2005). 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. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 23(30), pp. 7583-93.
Hess G, et al. 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. J Clin Oncol. 2005 Oct 20;23(30):7583-93. PubMed PMID: 16234522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Hess,Georg, AU - Bunjes,Donald, AU - Siegert,Wolfgang, AU - Schwerdtfeger,Rainer, AU - Ledderose,Georg, AU - Wassmann,Barbara, AU - Kobbe,Guido, AU - Bornhäuser,Martin, AU - Hochhaus,Andreas, AU - Ullmann,Andrew J, AU - Kindler,Thomas, AU - Haus,Ulrike, AU - Gschaidmeier,Harald, AU - Huber,Christoph, AU - Fischer,Thomas, PY - 2005/10/20/pubmed PY - 2005/12/13/medline PY - 2005/10/20/entrez SP - 7583 EP - 93 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 23 IS - 30 N2 - 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. SN - 0732-183X UR - https://www.unboundmedicine.com/medline/citation/16234522/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_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2005.01.3110?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -