scholarly journals Navigating Challenges in Monitoring Chronic Myeloid Leukemia with Multiple BCR-ABL1 Transcripts

2021 ◽  
pp. 1707-1711
Author(s):  
Brittany M. Smith ◽  
Diana Brewer ◽  
Brian J. Druker ◽  
Theodore P. Braun
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Term Treatment ◽  
Response To Therapy ◽  
Duration Of Treatment ◽  
Transcript Quantification ◽  
Long Term Treatment

Quantitative PCR-based strategies are typically effective for monitoring BCR-ABL1 transcript levels in chronic myeloid leukemia (CML). Additionally, some patients treated with tyrosine kinase inhibitors can experience long-term treatment-free remission after discontinuation of the inhibitor. However, this outcome hinges on effectively monitoring the patient’s response to therapy. We present a patient with CML and multiple BCR-ABL1 transcripts, including a rare isoform that lacks qPCR standardization. We describe unexpected discrepancies in transcript quantification, further having an impact on clinical decision-making regarding duration of treatment. To better inform clinical practice, we suggest monitoring patients at the same testing facility to better track transcript trend.

scholarly journals BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia

2017 ◽  
Vol 24 (6) ◽  
pp. 433-452 ◽  
Author(s):  
Sandra Cuellar ◽  
Michael Vozniak ◽  
Jill Rhodes ◽  
Nicholas Forcello ◽  
Daniel Olszta
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Patient Centered ◽  
Long Term Treatment

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug–drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug–drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug–drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist–patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

Front-line use of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: Practice considerations

2019 ◽  
Vol 26 (1) ◽  
pp. 156-174
Author(s):  
Michael J Reff ◽  
Alexandra Shillingburg ◽  
Bhavesh Shah ◽  
Christopher Elder ◽  
Hillary Prescott ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Clinical Decision Making ◽  
Chronic Phase ◽  
Response To Treatment ◽  
Healthcare Team ◽  
Long Term Treatment

The development of BCR-ABL-targeting tyrosine kinase inhibitors has transformed chronic phase chronic myeloid leukemia (CP CML) from a disease with a terminal prognosis to a treatable chronic illness. Long-term treatment with tyrosine kinase inhibitors means that patients have to be clinically managed and monitored over extended periods of time, thus a patient-centered, medically integrated, and multidisciplinary oncology healthcare team is required to support patients through their journey. Pharmacists work with patients, physicians, and the wider support team to select the optimum therapy plan for a given patient. These decisions are based on risk factors, comorbidities, concomitant medications, and personal circumstances and pharmacists advise on the efficacy and safety of different treatment options. Additionally, pharmacists are a key point-of-contact and resource for monitoring patient response to treatment, identifying and managing adverse events and drug–drug interactions, any subsequent therapy plan modifications, and, potentially, treatment-free remission. Pharmacists also assist with patient education, medication adherence, and financial discussions with patients throughout the long course of the disease. This review provides an overview of BCR-ABL tyrosine kinase inhibitors, discusses the role of the medically integrated pharmacy team, and suggests strategies that pharmacists can use in patient management and clinical decision-making to optimize the treatment of CP CML.

scholarly journals Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 243-247
Author(s):  
Delphine Rea
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Treatment Free Remission

Abstract The paradigm for managing patients with chronic myeloid leukemia is evolving. In the recent past, restoring a normal life expectancy while patients are receiving never-ending targeted therapy with BCR–ABL1 tyrosine kinase inhibitors through prevention of progression to blast phase and mitigation of iatrogenic risks was considered the best achievable outcome. Now, long-term treatment-free remission with continued response off tyrosine kinase inhibitor therapy is recognized as the most optimal benefit of treatment. Indeed, numerous independent clinical trials provided solid proof that tyrosine kinase inhibitor discontinuation was feasible in patients with deep and sustained molecular responses. This article discusses when tyrosine kinase inhibitors may be safely stopped in clinical practice on the basis of the best and latest available evidence.

scholarly journals Shedding Light on Targeting Chronic Myeloid Leukemia Stem Cells

2021 ◽  
Vol 10 (24) ◽  
pp. 5805
Author(s):  
Mohammad Houshmand ◽  
Alireza Kazemi ◽  
Ali Anjam Najmedini ◽  
Muhammad Shahzad Ali ◽  
Valentina Gaidano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Leukemia Stem Cells ◽  
Hematopoietic Stem ◽  
Long Term Treatment ◽  
Treatment Free Remission

Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors (TKI). When TKI therapy is discontinued in CML patients in deep, sustained and apparently stable molecular remission, these cells in approximately half of the cases restart to grow, resuming the leukemic process. The elimination of these TKI resistant leukemic stem cells is therefore an essential step in increasing the percentage of those patients who can reach a successful long-term treatment free remission (TFR). The understanding of the biology of the LSCs and the identification of the differences, phenotypic and/or metabolic, that could eventually allow them to be distinguished from the normal hematopoietic stem cells (HSCs) are therefore important steps in designing strategies to target LSCs in a rather selective way, sparing the normal counterparts.

scholarly journals Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?

2020 ◽  
Vol 4 (21) ◽  
pp. 5589-5594
Author(s):  
Delphine Rea
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Treatment Free Remission

Abstract The paradigm for managing patients with chronic myeloid leukemia is evolving. In the recent past, restoring a normal life expectancy while patients are receiving never-ending targeted therapy with BCR–ABL1 tyrosine kinase inhibitors through prevention of progression to blast phase and mitigation of iatrogenic risks was considered the best achievable outcome. Now, long-term treatment-free remission with continued response off tyrosine kinase inhibitor therapy is recognized as the most optimal benefit of treatment. Indeed, numerous independent clinical trials provided solid proof that tyrosine kinase inhibitor discontinuation was feasible in patients with deep and sustained molecular responses. This article discusses when tyrosine kinase inhibitors may be safely stopped in clinical practice on the basis of the best and latest available evidence.

Successful use of long-term follow-up in patients with chronic myeloid leukemia with a deep molecular response at reduced doses of 2nd generation tyrosine kinase inhibitors: clinical cases and literature review

2020 ◽  
Vol 92 (7) ◽  
pp. 90-94
Author(s):  
M. A. Gurianova ◽  
E. Yu. Chelysheva ◽  
O. A. Shukhov ◽  
A. G. Turkina
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Molecular Response ◽  
Long Term Treatment ◽  
Deep Molecular Response

Therapy with tyrosine kinase inhibitors (TKI) allows to achieve a deep molecular response in 6070% of patients with chronic myeloid leukemia (CML). According to the current guidelines CML patients receive a long-term treatment with TKI in standard dose. The frequently observed adverse effects (AE) of TKI therapy are mostly dose-dependent. A new treatment approach with TKI use in reduced dose is desirable for the CML patients with existing AE or with a high risk of AE occurrence. We report the two cases of successful long-term treatment of CML patients with reduced doses of second generation TKIs. The aim of the TKI dose reduction was to reduce the clinical manifestations of drug toxicities and to prevent the AE.

scholarly journals RT-qPCR versus Digital PCR: How Do They Impact Differently on Clinical Management of Chronic Myeloid Leukemia Patients?

2020 ◽  
Vol 13 (3) ◽  
pp. 1263-1269 ◽  
Author(s):  
Camilla Zanaglio ◽  
Simona Bernardi ◽  
Lisa Gandolfi ◽  
Mirko Farina ◽  
Federica Re ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Digital Pcr ◽  
Response To Therapy ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Molecular Response ◽  
Additional Specimen

Real-time quantitative PCR (RT-qPCR) is the gold standard to quantify the BCR-ABL1 transcript for molecular response monitoring in chronic myeloid leukemia (CML) patients, and it plays a pivotal role in clinical decision-making process, even if it presents technical limits. Increasing data suggest that digital PCR (dPCR) is more accurate and reliable than RT-qPCR in CML minimal residual disease monitoring and in patients’ selection for treatment discontinuation. But what about the identification of treatment discontinuation failures? We present the case of a CML patient enrolled both in a study aiming to comparatively assess molecular response by RT-qPCR and dPCR and in the progressive arm of the OPTkIMA trial. This is a phase III trial including CML patients randomized to receive a fixed versus a progressive intermittent tyrosine kinase inhibitor regimen. At 24 months, because of two consecutive detections of MR<sup>2.0</sup> by RT-qPCR, the patient resumed daily treatment. Conversely, dPCR revealed a stability of molecular response and even a slight decreasing of transcript over time. An additional specimen was sampled one month after the first MR<sup>2.0</sup> detection because of clinical decision: RT-qPCR resulted MR<sup>3.0</sup> and dPCR confirmed the transcript’s stability. Nowadays, the resumption of therapy is RT-qPCR-driven despite its limits in detection and robustness. In this case, according to dPCR, the patient could have continued intermittent treatment and the stability of response was then confirmed by RT-qPCR. So, dPCR could be able to better identify peculiar clinical response to therapy.

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