Intermittent Dosing Of Gleevec Is Efficacious In Cases Of Childhood Chronic Myeloid Leukemia With Poor Compliance

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5182-5182 ◽  
Author(s):  
Maria Moschovi ◽  
Maria Adamaki ◽  
Anastasia Athanasiadou ◽  
Archontis Zampogiannis ◽  
Natalia Tourkantoni
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Poor Compliance ◽  
Prolonged Treatment ◽  
Wide Range

Abstract Chronic myeloid leukemia (CML) is rare in childhood (less than 5% of all childhood leukemias). The main characteristic is the Philadelphia chromosome (BCR-ABL1 positive) and the tyrosine kinase inhibitor imatinib mesylate (Gleevec) is the treatment of choice, with the target oral dose being 440 mg/m2/day asdetermined by the COG-P9973 and COG-ADVL0122 trials, while allogeneic stem cell transplantation is postponed until CML becomes refractory to the drug. We administer a treatment dose of 400mg/m2/day but we have observed high toxicity levels associated with prolonged treatment. We present a girl with CML, with persistent residual disease (MRD), even two years following diagnosis, and serious side effects (dry skin, significant hair loss, gastrointestinal discomfort and diarrhoea) that affected her quality of life. The patient was tested for polymorphisms in the tyrosine kinase and was found negative. Careful interviewing of the family revealed that the persistent MRD was due to poor compliance of the patient to the therapeutic regimen. The child was unhappy due to the side effects and refused to take her pills (Gleevec), hence the poor compliance. Therefore, taking into consideration the child’s wellbeing and psychological welfare, it was decided that she would receive the drug on alternate months (one on/one off). Gleevec was discontinued when the patient completed two years of being MRD negative. The patient remains in complete molecular remission four years after the discontinuation of Gleevec. To date, there are few reports on childhood CML so most data come from studies in adults. Even though Gleevec is currently implemented as the primary treatment method in children, there are still doubts as to whether it can result in a permanent cure and of the potential complications of long-term use in the growth and development of these children. No specific guidelines have been set on the dosage and duration of treatment with Gleevec, especially for childhood CML patients facing a potentially lifelong treatment, who might also be faced with a wide range of unknown side effects. Psychological factors should also be taken into account and special attention should be given in avoiding adverse effects that interfere with the quality of life and the psychological welfare of this extremely fragile population. Overall, in our case, despite the persistent MRD, intermittent dosing of Gleevec proved to be an efficient method both in keeping toxicity levels to a minimum and in achieving complete and continuous remission. Persistent MRD levels in this case were due to the interrupted treatment regime, i.e. due to poor compliance, and not due to additional cytogenetic abnormalities that were resistant to Gleevec. Future clinical trials in children should investigate whether intermittent dosing of the drug produces fewer side effects during the course of treatment and whether it may present a more favourable option when considering the normal growth development of the children treated for CML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Specificity of dermatological adverse events of BCR-ABL tyrosine kinase inhibitors and their effect on quality of life of patients with chronic myeloid leukemia

2020 ◽  
pp. 72-76
Author(s):  
E. A. Shatokhina ◽  
A. G. Turkina ◽  
E. Yu. Chelysheva ◽  
O. A. Shukhov ◽  
A. N. Petrova ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Maculopapular Rash ◽  
Abl Tyrosine Kinase

Introduction. BCR-ABL tyrosine kinase inhibitors are currently used to successfully treat chronic myeloid leukemia (CML). Drug therapy is carried out in a continuous daily mode throughout the patient’s life. Treatment with this group of drugs is associated with specific dermatological adverse events (dAE), which can lead to a change in the regimen of effective, vital therapy for CML patients.Purpose. To study the characteristics of dermatological adverse events, the severity and influence on the quality of life of BCR-ABL tyrosine kinase inhibitors.Patients and methods. The observational study included 93 patients. The clinical manifestations of dAE, their severity were evaluated, their photographs and pathomorphological studies of skin biopsy samples were performed, cases of dose reduction or drug withdrawal due to dAE were recorded. The quality of life of patients with dAE was determined based on the assessment of the dermatological index of quality of life.Results. Imatinib therapy was accompanied by a maculopapular rash in 43.3 % of patients, nilotinib caused follicular keratosis in 12.9 % of patients. In 3.2 % of patients, dasatinib caused hyperpigmentation, in 2.2 % of patients lichenoid rashes of the II degree occurred during treatment with bosutinib. Ponatinib treatment was followed by dAE in 9.7 % of patients. All dAE have an impact on the quality of life of patients, but the maculopapular rash and dyskeratotic changes are most pronounced. In a pathomorphological study, these dAE have specific features corresponding to immuno-mediated dermatitis.Conclusions. The most frequent and pronounced dAE that significantly affect the quality of life of patients with CML are a maculopapular rash and dyskeratotic skin changes: psoriasiform and lichenoid dermatitis. Clinical and pathomorphological characteristics of skin reactions make it possible in the future to determine effective methods of supportive therapy for dAE.

scholarly journals Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison

2012 ◽  
Vol 21 (4) ◽  
pp. 1097-1103 ◽  
Author(s):  
Kristin M. Phillips ◽  
Javier Pinilla-Ibarz ◽  
Eduardo Sotomayor ◽  
Morgan R. Lee ◽  
Heather S. L. Jim ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Life Outcomes ◽  
Quality Of Life Outcomes

scholarly journals The value of quality of life assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitors

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 170-179 ◽  
Author(s):  
Fabio Efficace ◽  
Laura Cannella
Keyword(s):  
Quality Of Life ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Symptom Burden ◽  
Life Assessment ◽  
Patient Reported

Abstract The development of the oral tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML) is one of the great triumphs of cancer research. Although the efficacy of TKIs has dramatically improved the disease-specific overall survival rate, the prevalence of CML is increasing worldwide. Currently, CML patients receive prolonged (even lifelong) treatment, and over the last decade, clinical decision making has become challenging. Therefore, consideration of the effects of TKI therapies on patients’ quality of life (QoL) and symptom burden (ie, patient-reported outcomes [PROs]) is now critical to more robustly inform patient care and improve health care quality. Over the last 5 years, a number of studies have generated valuable PRO data, for example, on long-term QoL effects of imatinib therapy or symptom burden of patients switching from imatinib to second-generation TKIs. PRO findings are important, as they provide a unique patient perspective on the burden of the disease and treatments effects. We will review main evidence-based data on the use of PROs in clinical research and highlight the importance of methodological rigor of PRO assessment. Also, we will describe the potential value of using PRO assessment in routine clinical practice, for example, to facilitate timely management of side effects. Areas for future research will also be discussed.

Tyrosine-Kinase Inhibitors, Quality of Life and Symptom Burden in Chronic Myeloid Leukemia: What Have We Learned So Far?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4236-4236
Author(s):  
Fabio Efficace ◽  
Annarita Cardoni ◽  
Francesco Cottone ◽  
Marco Vignetti ◽  
Franco Mandelli
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Symptom Burden ◽  
Informed Treatment

Abstract Abstract 4236 BACKGROUND: Tyrosine kinase inhibitors (TKIs) have revolutionized treatment of chronic myeloid leukemia (CML) patients and quality of life (QoL) data can be of crucial importance in the current CML arena to make more informed treatment decisions. To date, a number of biomedical and laboratory data have been accumulated on clinical efficacy and toxicity of various TKIs; however, there is paucity of data on the impact of TKIs on patient outcomes. AIMS: The main objective of this systematic review is thus to quantify and to summarize all studies that have included QoL, or any other type of patient-reported outcomes (PROs) in patients with CML treated with TKIs. METHODS: A systematic review was performed, following the Cochrane methodology on all studies conducted in CML that have assessed QoL or any other type of PRO (e.g., symptom burden). The search was conducted on all full length manuscripts published up to November 2012. Candidate articles were identified mainly by PubMed, the Cochrane Library, PsycINFO and PsyArticles. Criteria for selection of studies were as follow. Types of participants: Patients diagnosed with CML, regardless of patients' age and the stage of the disease. Types of intervention: All treatments with TKIs, either used alone or in combination with other drugs. Types of outcome measures examined: Any studies including PROs were considered. Studies addressing adherence to therapy were not included. Types of studies: All type of studies were considered regardless of the design (e.g., prospective or cross-sectional study). No restriction in the number of enrolled patients or type of analysis (e.g. qualitative or quantitative) was applied. Two reviewers independently evaluated all candidate abstracts retrieved from electronic databases based on the above selection criteria. Extracted data from full length manuscripts were crosschecked and discrepancies resolved by consensus. The reviewers abstracted a number of basic features of the studies, including the type of treatment, the measures used to assess QoL and clinical characteristics of patients enrolled. Also, a summary of main PROs findings was provided. RESULTS: Six studies, enrolling overall 2171 CML patients, were identified up to November 2012. None of these studies were published before 2003. Out of six studies, two were conducted on a national level and four recruited patients in an international setting. Four studies reported QoL data of patients treated with imatinib, one on bosutinib and the other one included patients receiving various TKIs. QoL of patients younger than 60 years, who are in treatment with long-term imatinib therapy is greatly impaired when compared with that of their peers in the general population. This study suggests that although the less toxic profile of TKIs therapies is unquestionable, still much has to be done to further improve patient's QoL and reduce symptom burden. Also, another study suggested that fatigue is the main factor influencing QoL regardless of the type of TKIs. Some data also indicates that physicians might underestimate the importance of symptoms. Another study, conducted in patients treated with bosutinib, showed that QoL profile of patients who have failed first line Imatinib therapy, due to either resistance or intolerance, is not different. Second line therapy with bosutinb provide clinically meaningful QoL improvements in imatinib-intolerant patients (but not in imatinib-resistant patients). Remarkably, no study was identified measuring QoL, or any other type of PROs, in patients treated with dasatinib or nilotinib. Two studies reported a gender effect, showing that male tend to report better QoL outcomes than female patients. CONCLUSIONS: This systematic review revealed the paucity of evidence base data in this area. However, QoL assessments in these CML studies emphasize the unique information provided by the patient's perspective on the burden of the disease and treatment. Investigators are encouraged to include PROs in future CML studies to obtain additional meaningful data to make more informed treatment decisions. Disclosures: Efficace: Novartis: Research Funding; Bristol Myers Squibb: Honoraria.

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