scholarly journals Chronic Myeloid Leukemia with e19a2BCR-ABL1Transcripts and Marked Thrombocytosis: The Role of Molecular Monitoring

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Stephen E. Langabeer ◽  
Sarah L. McCarron ◽  
Johanna Kelly ◽  
Janusz Krawczyk ◽  
Suzanne McPherson ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Patient Management ◽  
Kinase Inhibitor ◽  
Favourable Outcome ◽  
Molecular Monitoring ◽  
Real Time Quantitative Pcr ◽  
Treatment Interruptions ◽  
Dose Reductions

While most patients with chronic myeloid leukemia (CML) express either e13a2 or e14a2BCR-ABL1transcripts, a significant minority expresses variant transcripts, of which e19a2 is the most common. Although considered to have a relatively favourable outcome, reported responses to tyrosine kinase inhibitor (TKI) therapy are variable with molecular monitoring in CML patients with e19a2BCR-ABL1transcripts rarely reported. A case of e19a2BCR-ABL1CML with marked thrombocytosis is described in which the value of molecular monitoring is emphasised during treatment interruptions, dose reductions, and changes. This case serves to demonstrate the requirement for prospective real-time quantitative PCR (RQ-PCR) assays for patients with variantBCR-ABL1transcript types and standardisation of such assays to enable modern patient management.

scholarly journals A Retrospective Analysis about Frequency of Monitoring in Italian Chronic Myeloid Leukemia Patients after Discontinuation

2020 ◽  
Vol 9 (11) ◽  
pp. 3692
Author(s):  
Matteo Dragani ◽  
Giovanna Rege Cambrin ◽  
Paola Berchialla ◽  
Irene Dogliotti ◽  
Gianantonio Rosti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Molecular Response ◽  
Molecular Monitoring ◽  
Delay In Diagnosis ◽  
Number Of Patients

Successful discontinuation of tyrosine kinase inhibitors has been achieved in patients with chronic-phase chronic myeloid leukemia (CML). Careful molecular monitoring after discontinuation warrants safe and prompt resumption of therapy. We retrospectively evaluated how molecular monitoring has been conducted in Italy in a cohort of patients who discontinued tyrosine kinase inhibitor (TKI) treatment per clinical practice. The outcome of these patients has recently been reported—281 chronic-phase CML patients were included in this subanalysis. Median follow-up since discontinuation was 2 years. Overall, 2203 analyses were performed, 17.9% in the first three months and 38.4% in the first six months. Eighty-six patients lost major molecular response (MMR) in a mean time of 5.7 months—65 pts (75.6%) during the first six months. We evaluated the number of patients who would experience a delay in diagnosis of MMR loss if a three-month monitoring schedule was adopted. In the first 6 months, 19 pts (29.2%) would have a one-month delay, 26 (40%) a 2-month delay. Very few patients would experience a delay in the following months. A less intense frequency of monitoring, particularly after the first 6 months off treatment, would not have affected the success of treatment-free remission (TFR) nor put patients at risk of progression.

Diagnosing and Managing Advanced Chronic Myeloid Leukemia

2015 ◽  
pp. e381-e388 ◽  
Author(s):  
Michael W. Deininger
Keyword(s):  
Gene Expression ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Chronic Phase ◽  
Clinical Staging ◽  
Molecular Monitoring ◽  
Hematopoietic Stem

Clinical staging of chronic myeloid leukemia (CML) distinguishes between chronic phase (CP-CML), accelerated phase (AP-CML), and blastic phase (BP-CML), reflecting its natural history in the absence of effective therapy. Morphologically, transformation from CP-CML to AP/BP-CML is characterized by a progressive or sudden loss of differentiation. Multiple different somatic mutations have been implicated in transformation from CP-CML to AP/BC-CML, but no characteristic mutation or combination of mutations have emerged. Gene expression profiles of AP-CML and BP-CML are similar, consistent with biphasic evolution at the molecular level. Gene expression of tyrosine kinase inhibitor (TKI)–resistant CP-CML and second CP-CML resemble AP/BP-CML, suggesting that morphology alone is a poor predictor of biologic behavior. At the clinical level, progression to AP/BP-CML or resistance to first-line TKI therapy distinguishes a good risk condition with survival close to the general population from a disease likely to reduce survival. Progression while receiving TKI therapy is frequently caused by mutations in the target kinase BCR-ABL1, but progression may occur in the absence of explanatory BCR-ABL1 mutations, suggesting involvement of alternative pathways. Identifying patients in whom milestones of TKI response fail to occur or whose disease progress while receiving therapy requires appropriate molecular monitoring. Selection of salvage TKI depends on prior TKI history, comorbidities, and BCR-ABL1 mutation status. Despite the introduction of novel TKIs, therapy of AP/BP-CML remains challenging and requires accepting modalities with substantial toxicity, such as hematopoietic stem cell transplantation (HSCT).

scholarly journals Complex cytogenetic abnormalities in chronic myeloid leukemia resulting in early progression to blast crisis: a case report

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Haider Ali Malakzai ◽  
Soma Rahmani ◽  
Ahmed Maseh Haidary ◽  
Sarah Noor ◽  
Maryam Ahmad ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Patient Management ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
Marker Chromosome ◽  
Initial Response ◽  
Response To Therapy ◽  
Cytogenetic Abnormalities ◽  
Cytogenetic Monitoring

Abstract Introduction BCR-ABL1, resulting from t(9;22), is the oncogenic driver of chronic myeloid leukemia and the therapeutic target of the disease. Molecular studies have been the gold standard modality for patient assessment since the advent of tyrosine kinase inhibitor therapy. In spite of that, there are cytogenetic abnormalities that can render the disease unresponsive to conventional therapy, thus making cytogenetics an important component of patient management guidelines. Case presentation We present a case of a Tajik, Afghan patient with chronic myeloid leukemia with del(6)(q23.3q27), t(9;22)(q34;q11.2), monosomy 11, monosomy 12, and marker chromosome who, despite having typical clinical and hematological disease with initial response to therapy, progressed to blast crisis very early and thus required special interventions. Conclusion Cytogenetic monitoring is an important pillar in the management of patients with chronic myeloid leukemia that cannot be ignored. It should therefore be a part of patient management not only during diagnosis but also during management. We present an unusual cytogenetic abnormality in a patient with chronic myeloid leukemia that resulted in early disease progression.

scholarly journals MONITORING THE RESPONSE TO TYROSINE KINASE INHIBITOR (TKI) TREATMENT IN CHRONIC MYELOID LEUKEMIA (CML)

2013 ◽  
Vol 6 (1) ◽  
pp. e2014009 ◽  
Author(s):  
Ibrahim C. Haznedaroglu
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Critical Time ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Molecular Monitoring ◽  
Tki Treatment

The aim of oral tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is to get ideal hematological, cytogenetic, molecular responses at the critical time-points. The depth of the response obtained with TKI and time to achieve this response are important for the prediction of prognosis in the patient with CML. The high efficacy of the TKI treatment of CML has prompted the need for accurate methods to monitor response at levels below the landmark of CCyR. Quantification of BCR-ABL transcripts has proven to be the most sensitive method available and has shown prognostic impact with regard to progression-free survival. European LeukemiaNet (ELN) molecular program harmonized the reporting of results according to the IS (Internatıonal harmonization of Scale) in Europe. The aim of this review is to outline monitoring the response to optimal TKI treatment based on the ELN CML 2013 recommendations from the clinical point of view as a physician. Careful cytogenetic and molecular monitoring could help selecting the most convenient TKI drug and to optimize TKI treatment. Excessive monitoring may have an economical cost but failure to optimize TKI treatment may result in CML disease acceleration and death.

scholarly journals Timely Molecular Monitoring and Achievement of Major Molecular Response in Chronic Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3072-3072
Author(s):  
Adi J. Klil-Drori ◽  
Laurent Azoulay ◽  
Hui Yin ◽  
Alexa Del Corpo ◽  
Michaël Harnois ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Treatment Guidelines ◽  
Patient Adherence ◽  
Point Estimate ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Molecular Monitoring

Abstract Background: Timely molecular monitoring is the cornerstone of chronic myeloid leukemia (CML) treatment guidelines. These guidelines are based on the design of clinical trials, but none have been validated prospectively. We hypothesized that timely molecular monitoring in routine patient care increases the likelihood of achieving major molecular response (MMR) in CML. Methods: We conducted a prospective cohort study using the Québec CML Registry, which comprises 713 patients from 16 hospitals. Patients with newly-diagnosed CML (2009-2014) and measurable disease by quantitative PCR were followed from tyrosine kinase inhibitor (TKI) initiation. Timely PCR (tPCR) was defined as a PCR performed at 2-4, 11-13, and 17-19 months. (Figure). Study outcome was the achievement of MMR at 25 months, defined as international scale ratio (IS) <0.1% or a 3-log reduction in BCR-ABL1 copy number. Achievement of MMR was determined using any PCR during follow-up. Generalized estimating equations (GEE) using an exchangeable correlation structure, to account for patient clustering by center, were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of achieving MMR comparing adherence and nonadherence to tPCR. The models were adjusted for age, sex, first-line TKI, year of study entry, and Charlson comorbidity index. Results: A total of 246 patients with 25 months of follow-up were included in the analysis (Table 1). Patients were excluded due to diagnoses before 2009 (350), insufficient follow-up (76), and other (41). The mean (standard deviation) age was 56.1 (15.5), 43.9% were female; 67.5% were started on imatinib, and 47.6% were treated in higher-volume (>50 CML patients) centers. Timely PCRs were performed in 76.3%, 69.5%, and 61.0% of patients at 2-4, 11-13, and 17-19 months, respectively. When compared with not performing tPCRs, performing one and two tPCRs were associated with achieving an MMR by 25 months (OR: 17.05, 95% CI: 5.18-56.09 and OR: 14.96, 95% CI 3.63-61.73, respectively, Table 2). The highest OR of achieving MMR was observed among those who underwent three tPCRs (OR: 24.02, 95% CI: 7.07-81.55). Conclusions: To our knowledge, this is the first study to assess clinical outcomes associated with timely molecular monitoring in early CML. While performing one and two tPCRs was associated with achieving MMR at 25 months, the point estimate for performing three tPCRs was the highest. These findings indicate that timely monitoring may allow for faster switching of TKI, which ultimately permits patients with early failure to "catch up." Alternatively, more regular testing may increase patient adherence to therapy. If replicated, these findings support routine and punctual monitoring of patients on TKI therapy. Disclosures Assouline: Pfizer: Speakers Bureau; BMS: Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document