scholarly journals Analyzing the impact of pregnancy on the outcomes of childbearing age women with chronic myeloid leukemia

2021 ◽  
Author(s):  
Fernanda Maria Santos ◽  
Giovanna Ghelfond ◽  
Fernanda Salles Seguro ◽  
Andre Neder R. Abdo ◽  
Thales Dalessandro ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Childbearing Age ◽  
Childbearing Age Women ◽  
The Impact

scholarly journals DNA Methylation and Intra-Clonal Heterogeneity: The Chronic Myeloid Leukemia Model

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3587
Author(s):  
Benjamin Lebecque ◽  
Céline Bourgne ◽  
Véronique Vidal ◽  
Marc G. Berger
Keyword(s):  
Dna Methylation ◽  
Chronic Myeloid Leukemia ◽  
Fusion Protein ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Single Gene ◽  
Clonal Heterogeneity ◽  
Sequencing Technologies ◽  
Genome Wide ◽  
The Impact

Chronic Myeloid Leukemia (CML) is a model to investigate the impact of tumor intra-clonal heterogeneity in personalized medicine. Indeed, tyrosine kinase inhibitors (TKIs) target the BCR-ABL fusion protein, which is considered the major CML driver. TKI use has highlighted the existence of intra-clonal heterogeneity, as indicated by the persistence of a minority subclone for several years despite the presence of the target fusion protein in all cells. Epigenetic modifications could partly explain this heterogeneity. This review summarizes the results of DNA methylation studies in CML. Next-generation sequencing technologies allowed for moving from single-gene to genome-wide analyses showing that methylation abnormalities are much more widespread in CML cells. These data showed that global hypomethylation is associated with hypermethylation of specific sites already at diagnosis in the early phase of CML. The BCR-ABL-independence of some methylation profile alterations and the recent demonstration of the initial intra-clonal DNA methylation heterogeneity suggests that some DNA methylation alterations may be biomarkers of TKI sensitivity/resistance and of disease progression risk. These results also open perspectives for understanding the epigenetic/genetic background of CML predisposition and for developing new therapeutic strategies.

The Impact of Symptom Burden on Patient Quality of Life in Chronic Myeloid Leukemia

Oncology ◽  
2014 ◽  
Vol 87 (3) ◽  
pp. 133-147 ◽  
Author(s):  
David Cella ◽  
Cindy J. Nowinski ◽  
Olga Frankfurt
Keyword(s):  
Quality Of Life ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Symptom Burden ◽  
The Impact

scholarly journals The impact of introducing tyrosine kinase inhibitors on chronic myeloid leukemia survival: a population-based study

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Enza Di Felice ◽  
Francesca Roncaglia ◽  
Francesco Venturelli ◽  
Lucia Mangone ◽  
Stefano Luminari ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Population Based ◽  
Population Based Study ◽  
The Impact

scholarly journals PCN217 THE IMPACT OF ORAL ONCOLYTIC PARITY LEGISLATION ON ADHERENCE AND OUT-OF-POCKET SPENDING IN CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 23 ◽  
pp. S60
Author(s):  
A. Spargo ◽  
C. Yost ◽  
P. Squires ◽  
A. Raju ◽  
B. Schroader ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
The Impact

scholarly journals PF401 IMMUNE SYSTEM AND CHRONIC MYELOID LEUKEMIA: THE IMPACT OF TYROSINE KINASE INHIBITORS

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 152-153
Author(s):  
R.S. Alves ◽  
S.E. McArdle ◽  
J. Vadakekolathu ◽  
A.C. Gonçalves ◽  
P. Freitas-Tavares ◽  
...  
Keyword(s):  
Immune System ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
The Impact

HSR19-090: Changes in Adherence to Tyrosine Kinase Inhibitor Treatment Patterns Among Patients With Chronic Myeloid Leukemia and the Impact on Costs: 2001–2017

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-090
Author(s):  
Henry J. Henk ◽  
Lena E. Winestone ◽  
Jennifer J. Wilkes ◽  
Laura Becker ◽  
Pamela Morin ◽  
...  
Keyword(s):  
Health Care ◽  
Chronic Myeloid Leukemia ◽  
Healthcare Costs ◽  
Myeloid Leukemia ◽  
First Line ◽  
Tki Treatment ◽  
The Impact ◽  
Care Costs ◽  
Over Time ◽  
Privately Insured

Background: Chronic myeloid leukemia (CML) treatment improved considerably after introduction of oral tyrosine kinase inhibitors (TKI). As a result, the number of patients living with CML may reach 250,000 by 2040. We track changes in TKI treatment adherence since 2001 and provide an early assessment of treatment costs following the availability of second-generation TKIs and generic imatinib. Methods: A retrospective cohort from the OptumLabs Data Warehouse, which includes claims data for privately insured and Medicare Advantage (MA) enrollees in a large private U.S. health plan with medical and pharmacy benefits, was used. Patients with CML initiated TKI treatment between May 2001 and October 2016 and were continuously enrolled in the health plan 6 months prior through 12 months following TKI start. Adherence was defined by medication possession ratio (MPR1=total days’ supply of imatinib in 1st year divided by 365, 1=perfect adherence). Total health care costs include medical and prescription medication benefits. MPR1 was modeled using ordinary least squares regression. The association between MPR1 and healthcare costs was estimated using a generalized linear model specified with a gamma error distribution and a log link. Results: We identified 1,793 eligible patients. First-line TKI has changed over time (dasatinib and nilotinib represent 45% of all 2016 starts; imatinib 55%). From 2001 to 2016, adherence increased (Table 1). MPR1 was higher in men and increased with age until age ∼62 after which it declined. MPR1 was lower for patients with more comorbid conditions prior to treatment. Overall, MPR1 was inversely associated with total health care costs (medical and pharmacy) among privately insured (P<.001) but not MA enrollees. The net impact of MPR1 on total healthcare costs diminished over time (P<.001) where a 10% point decrease in MPR1 was associated with 12% and 4% lower total costs, prior to and following availability of 2nd generation TKIs, respectively. When examining medical costs only, MPR1 was inversely associated with medical costs for both privately insured (P<.001) and MA enrollees (P=.016). Conclusions: We found that adherence to TKI treatment increased over time. While imatinib is still used more frequently than other TKIs as first-line therapy, second-generation TKIs are becoming increasingly used as first-line agents. Possible cost-offsets are decreasing over time but it may be too early to formally evaluate the impact of generic imatinib.

Retrospective Study of Trough Imatinib Plasma Levels Conducted as Part of the Follow-up of Patients with Chronic Myeloid Leukemia in a Canadian Cohort

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4258-4258
Author(s):  
Rahima Jamal ◽  
Danielle Desmarais ◽  
John Chapdelaine ◽  
Yvan Côté ◽  
Lambert Busque
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Plasma Concentrations ◽  
The Body ◽  
Inadequate Response ◽  
Molecular Responses ◽  
The Impact ◽  
Trough Levels

Abstract While imatinib biodisponibility is excellent, trough imatinib plasma levels associated with standard dose imatinib are variable and cannot be predicted by the age, the body surface area or the weight of the patient. Imatinib trough levels have recently been associated with both cytogenetic and molecular responses, making imatinib pharmacokinetics a possible target in optimisation of the treatment of patients with chronic myeloid leukemia. We retrospectively analysed trough imatinib plasma levels prescribed as part of the longitudinal follow-up of a cohort of patients with chronic myeloid leukemia in Canada. Indications for testing were inadequate response, important side effects or suspicion of non compliance. The objectives of the study were to evaluate the variability of trough imatinib plasma levels in our cohort and determine the impact a first result had on the subsequent plasma level in patients with more than one imatinib plasma determination. Analyses of trough plasma levels in 278 patients were conducted in a central canadian laboratory from April 2007 to April 2008. Trough imatinib plasma levels were measured using liquid chromatography and tandem mass spectrometry (LC/MS/MS) with deuterated imatinib as the internal standard. Distribution of trough imatinib plasma levels according to the established IRIS quartiles (Q1–Q4; BLOOD. 2008, vol 11, p4022)) showed an important variability, with plasma levels distributed between less than 100 ng/ml and more than 4500 ng/ml. Sixty-two (22.3%) patients in our cohort had plasma levels below 647 ng/ml (Q1), 101(36.3%) patients had levels between 647–1170 ng/ml (Q2–Q3) and 115 (41.3%) patients had trough levels above 1170 ng/ml (Q4). There were 31 patients (11.2%) with levels above 2000 ng/ml, all of whom were included in the Q4. Thirty seven patients in our cohort had more than one analysis of trough imatinib plasma levels done during the one year follow-up for a total of 82 analyses. Sub-group analysis of trough imatinib plasma levels was conducted in the 13 patients in the Q1 and the six patients in the Q4 who had 2 analyses done. Mean trough imatinib plasma levels went from 401ng/ml to 665 ng/ml in the Q1 patients and from 2845 ng/ml to 1065 ng/ml in the Q4 patients. These results confirm the feasibility of imatinib plasma levels testing in the community and the important variability of trough imatinib plasma concentrations in individual patients, as described by other groups. A significant portion of patients in our cohort had trough levels below 647 ng/ml, which has been associated with less favourable cytogenetic and molecular responses in studies. These results also suggest that physicians act on the information procured by the determination of imatinib plasma levels as second level determination was improved for patients initially in Q1 or Q4. Further follow up analyses are needed to document if optimisation of dosing leads to better response or improvement in tolerability of the drug.

Allogeneic Stem Cell Transplantation for Patients with Chronic Myeloid Leukemia After Prior Treatment with Nilotinib or Dasatinib

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2348-2348
Author(s):  
Michael Schleuning ◽  
Marijke Scholten ◽  
Anja van Biezen ◽  
Arnon Nagler ◽  
Jane F. Apperley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
The Impact

Abstract Abstract 2348 Stem cell transplantation (SCT) will continue to be a treatment option for patients with chronic myeloid leukemia, despite the introduction of tyrosine kinase inhibitors (TKI). However, many patients will have received prior therapy with TKI, including Nilotinib or Dasatinib at the time of allogeneic SCT. While the use of Imatinib prior to SCT seems to have no adverse impact on the outcome of allogeneic SCT little is known on the impact of prior use of second generation TKI. Therefore we conducted a retrospective registry study and identified 56 patients with CML who received an allotransplant after having been treated with Nilotinib and/or Dasatinib. Best responses to second generation TKI were major molecular response in 11%, complete cytogenetic response in 7%, partial cytogenetic response in 18%, complete hematologic remission in 25% and no response in 34%, respectively. At SCT, 37% of the patients were in accelerated or in blast phase, 36% in CP2 or higher and 27% in first chronic phase. Graft failure occurred in two patients. The median follow-up for surviving patients is 19 months. At 24 months the estimated non-relapse mortality was 33% and the relapse incidence 15%. Probability of survival is more than 85% at 2 years in patients transplanted in CP1. In univariate analysis there was a non significant trend in favor for pretreatment with Nilotinib as compared to the other groups. However, in multivariate analysis only stage of the disease was a predictor for survival. With respect to overall survival no significant differences could be identified for the following variables: patient age, donor type, stem cell source, intensity of the conditioning, time diagnosis to transplant, in or ex vivo T-cell depletion, response to treatment with second generation TKI. Patients transplanted in blast crisis had a significant higher risk of non relapse mortality. In summary, despite the shortcomings of a retrospective study, the data reported clearly show the feasibility and efficacy of allo SCT in patients pretreated with second generation TKI and it should be emphasized that the timing of allogeneic stem cell transplantation remains crucial to avoid unacceptable high treatment related mortality. Disclosures: Ekblom: Bristol-Myers Squibb: Honoraria.

Delayed Cytogenetic Response and Reduced Rate of Major Molecular Response Associated to Increased Body Mass Index At Baseline in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Imatinib.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2784-2784
Author(s):  
Massimo Breccia ◽  
Giuseppina Loglisci ◽  
Adriano Salaroli ◽  
Alessandra Serrao ◽  
Paola Volpicelli ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Body Mass ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Normal Weight ◽  
First Line ◽  
Reduced Rate ◽  
The Impact

Abstract Abstract 2784 Obesity, measured as body mass index (BMI), has been identified as a possible risk factor for the onset of several solid tumors as well as for chronic myeloid leukemia (CML). To date, no correlations have been reported in this latter disease between BMI at baseline and response to targeted therapies. We refer here on the impact of BMI on clinical response in CML. Three hundred and thirty-nine chronic phase (CP) CML patients treated with imatinib entered the study: 142 patients first received interferon alpha outside clinical trials and were then switched to imatinib for failure. For this group of patients, BMI was collected at the time of start of imatinib. The remaining patients were consecutively treated with imatinib first-line from January 2000 onward. BMI was defined as the individual's body weight divided by the square of his of her height and patients were categorised according to WHO into four categories: underweight (BMI < 18.5), normal weight (BMI 18.5-< 25), overweight (BMI 25-<30) and obese (BMI ≥ 30). All patients were followed according to ELN guidelines. We also analysed 25 CP-CML patients treated frontline with nilotinib. One hundred and fifty-six patients (46%) were categorized as underweight/normalweight, while 183 patients (54%) were classified as overweight/obese. BMI increased with age, with a median age of 29 years in underweight category, 43.4 years in normal weight, 54.9 years in overweight and 62.4 years in obese patients (p=0.001). We did not reveal statistically significant association between BMI and prognostic risk stratification at baseline, even when we used new EUTOS score, or type of BCR/ABL transcript. No statistically significant difference was revealed in terms of overall CCyR rate which was 87% for underweight/normal weight categories compared to 84% for overweight/obese group (p=0.34). If compared to patients with low BMI (< 18.5–25), patients with increased BMI (> 25–40) at diagnosis who received imatinib, showed a significantly longer median time to reach CCyR (6.8 months vs 3.3 months, p=0.01), a reduced rate of MMR (77% vs 58%, p=0.01) which was also achieved in a longer median time (29 months compared to 14 months, p=0.03). At 18 months, molecular kinetics revealed that median BCR-ABL/ABL ratio was 0.6% IS (range 0.001%-2%) in underweight/normal weight group compared to 1.6% IS (range 0.01%-3%) in overweight/obese category (p=0.01). Conversely, no differences were revealed with respect to BMI in patients treated frontline with nilotinib and also patients with increased BMI obtained rapidly CCyR and MMR, with an incidence similar to that of underweight/normal weight patients. These results suggest that CML patients with increased weight at baseline should be followed and carefully monitored if treated with standard dose imatinib frontline for a possible early switch to a second generation TKI or, as an alternative, should preferably be candidate to receive these drugs as a first line therapy. Disclosures: No relevant conflicts of interest to declare.

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