Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods

Kantarjian, Hagop M.; Schiffer, Charles A.; Jones, Dan; Cortés, Jorge E.

doi:10.1182/blood-2007-09-110189

Cited by 133 publications

(100 citation statements)

References 58 publications

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“…The diagnosis of typical CML is simple and consists of documenting, in the setting of persistent unexplained leukocytosis (or occasionally thrombocytosis), the presence of the Ph chromosome abnormality, the t(9;22)(q34;q11), by routine cytogenetics, or the Phrelated molecular BCR-ABL abnormalities by fluorescent in situ hybridization (FISH) or by molecular studies [12][13][14].…”

Section: Diagnosismentioning

confidence: 99%

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

2014

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Disease overview: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100,000 adults, and accounts for ∼15% of newly diagnosed cases of leukemia in adults. Diagnosis: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR‐ABL fusion oncogene, which in turn translates into a Bcr‐Abl oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib have been approved by the US Food and Drug Administration for the first‐line treatment of patients with newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; their impact on long‐term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second‐line options include second and third generation TKIs. Although second and third generation TKIs are potent and specific BCR‐ABL TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as patients comorbidities, disease stage, and BCR‐ABL mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib. Allogeneic transplantation remains an important therapeutic option for CML‐CP who have failed at least 2 TKIs, and for all patients in advanced phase disease. Am. J. Hematol. 89:547–556, 2014. © 2014 Wiley Periodicals, Inc.

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Section: Diagnosismentioning

confidence: 99%

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

2014

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“…31 Some investigators advocate mutational analysis for patients who experience a 2-fold to 10-fold rise in BCR-ABL transcript levels by quantitative PCR. 32 In a prospective study of 90 patients who had CML in CCyR on imatinib, an increase in BCR-ABL RNA levels >3.2-fold was a significant predictor of disease recurrence and may be an appropriate threshold for considering a change in therapy. 33 Conversely, in a more recent study, Kantarjian et al observed that, for most patients in CCyR during imatinib therapy, a rising transcript level did not generally increase the risk of progression.…”

Section: Imatinib Nilotinib Dasatinibmentioning

confidence: 99%

“…33 Conversely, in a more recent study, Kantarjian et al observed that, for most patients in CCyR during imatinib therapy, a rising transcript level did not generally increase the risk of progression. 32 Only those patients who lost an MMR or who never achieved an MMR were at increased risk for disease progression when transcript levels increased more than 1-log as determined by PCR.…”

Section: Imatinib Nilotinib Dasatinibmentioning

confidence: 99%

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

Kantarjian

Cortés

Rosée

et al. 2010

Cancer

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Identification of BCR‐ABL as the defining leukemogenic event in chronic myelogenous leukemia (CML) revolutionized the treatment of the disease. Imatinib, a potent BCR‐ABL inhibitor, is the standard of care for the first‐line treatment of patients with chronic‐phase CML because of its high long‐term response rates and favorable tolerability profile compared with previous standard therapies. However, resistance to imatinib develops in 2% to 4% of patients annually. For patients with acquired cytogenetic resistance to standard‐dose imatinib (400 mg daily), imatinib dose escalation (600‐800 mg daily) is an excellent first option for managing patients and achieving cytogenetic responses. However, for patients with primary resistance to imatinib, hematologic disease recurrence, or emergent BCR‐ABL kinase domain mutations, imatinib dose escalation may not be sufficient to control the disease. For these patients, the potent second‐generation tyrosine kinase inhibitors dasatinib and nilotinib are available. Both agents provide effective therapeutic options for patients with imatinib resistance or intolerance. For the current overview, the authors reviewed the data supporting the use of both dasatinib and nilotinib in imatinib‐resistant or imatinib‐intolerant patients, and they have highlighted the future of CML therapy. Overall, the article is intended to offer physicians a comprehensive review of the current literature and to provide data supporting various treatment options for patients with CML throughout the course of imatinib therapy and beyond. Cancer 2010. © 2010 American Cancer Society.

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“…The most commonly used first-line treatment for patients with CML is imatinib mesylate (Gleevec), an orally available, small-molecule inhibitor of BCR-ABL tyrosine kinase activity (Druker et al, 2001;O'Brien et al, 2003). Despite the proven efficacy and tolerability of imatinib, the development of resistance is a major clinical concern requiring regular monitoring of patients (Baccarani et al, 2008;Kantarjian et al, 2008) and represents an area of significant unmet medical need and drug development opportunity.…”

Section: Ph( þ ) Mpd: CMLmentioning

confidence: 99%