scholarly journals A Pharmacist-Led Oral Chemotherapy Program’s Impact on Chronic Myeloid Leukemia Patient Satisfaction, Adherence, and Outcomes

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Taylor Dennison, PharmD ◽  
Allison M. Deal, MS ◽  
Matthew Foster, MD ◽  
John Valgus, PharmD, MHA, BCOP ◽  
Benyam Muluneh, PharmD, BCOP, CPP
Keyword(s):  
Patient Satisfaction ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Myeloid Leukemia Patient ◽  
Oral Chemotherapy ◽  
Molecular Response ◽  
Patient Reported ◽  
Value Integration ◽  
Specialty Pharmacy

Patients with chronic myeloid leukemia (CML) can be treated with oral tyrosine kinase inhibitors (TKIs). Pharmacist-led oral chemotherapy programs (POCPs) can improve TKI adherence rates, but evaluation of patient satisfaction with such programs is rare. The purpose of this analysis was to compare the satisfaction of patients with CML taking TKIs enrolled in a POCP program with that of those not enrolled. Secondary objectives were to assess adherence rates, patient-reported value, early molecular response (EMR) rates, and major molecular response (MMR) rates. This study utilized an anonymous telephone survey of patients who had taken TKIs for at least 3 months. Molecular response was determined by chart review. Of 40 patients surveyed, 50% were enrolled in the POCP, and the POCP group had more African Americans than the non-POCP group. More patients in the POCP were satisfied with their care than in the non-POCP group (100% vs. 75%, p = .047). There were no differences in high patient-reported adherence (55% vs. 60%, p = 1.000), patient-reported value for integrated services (95% vs. 90%, p = 1.000), achievement of EMR (75% vs. 75%, p = 1.000), or MMR (85% vs. 85%, p = 1.000). Patients in the POCP received more structured clinical pharmacy services; however, both groups felt the clinical pharmacist played a major role in their care (85% vs. 90%, p = 1.000). Patients in the non-POCP group reported lower satisfaction than those enrolled resulting from fragmented care that was likely due to external specialty pharmacies. Irrespective of POCP enrollment, patients reported clinical pharmacists play a major role in their therapy and value integration of their specialty pharmacy and medical team.

scholarly journals Planned Pregnancy in a Chronic Myeloid Leukemia Patient in Molecular Remission

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Carolina Pavlovsky ◽  
Isabel Giere ◽  
Germán Van Thillo
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Chronic Myeloid Leukemia Patient ◽  
Molecular Response ◽  
Molecular Monitoring ◽  
Virtual Absence ◽  
Pregnancy And Delivery ◽  
Tki Treatment

Excellent response rates and a good quality of life have been observed since the introduction of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) treatment. Consequently, some challenges began to appear in CML women in child-bearing age wishing to become pregnant. Currently, many women around the world are in stable major/complete molecular response MMR/CMR (MMR: <0.1% BCR-ABL/ABL and CMR: undetectable BCR-ABL mRNA by RQ-PCR transcript levels on the international scale). The condition of stable MMR/CMR is linked to a long-term virtual absence of progression to the accelerated and blastic phase and to the possibility of stopping the TKI treatment with the maintenance of a condition of CMR in a proportion of cases. Imatinib teratogenic and prescribing information prohibits the use of it during pregnancy. We describe the case of a 36-year-old female patient with CML in chronic phase who stopped imatinib after 2 years in major molecular response (MMR) to plan a pregnancy. Molecular monitoring by RQ-PCR was performed quarterly. She achieved a safe pregnancy and delivery maintaining an optimal molecular response throughout the pregnancy. Isolated literature reports have been described, but no formal advice has been described at present time.

scholarly journals Chronic Myeloid Leukemia in Children and Adolescents: The Achilles Heel of Oncogenesis and Tyrosine Kinase Inhibitors

2021 ◽  
Vol 22 (15) ◽  
pp. 7806
Author(s):  
Maria Moschovi ◽  
Charikleia Kelaidi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Children And Adolescents ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Hematopoietic Cell Transplantation ◽  
Adult Life ◽  
Normal Growth ◽  
Molecular Response ◽  
Treatment Paradigm ◽  
Treatment Free Remission

Chronic myeloid leukemia (CML) is a rare disease in children and adolescents. The goal of therapy in children and adolescents is normal life expectancy, without compromising normal growth and development and potential for achievement of milestones in adult life. The perspective of cure is also reflected in the goal of treatment-free remission, with its surrogate markers, such as deep molecular response, also becoming the new endpoints of therapy efficacy in children and adolescents. Chronic myeloid leukemia was a fatal disease to children and adolescents in the past. Following the treatment paradigm of imatinib, it became a chronic disease with the potential of complete remission and even cure without the long-term hazards of allogeneic hematopoietic cell transplantation. The diagnosis and treatment of CML affect a child’s trajectory through life and important physiological events like development and procreation.

scholarly journals Meta-Analysis of Gastrointestinal Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1643
Author(s):  
Prahathishree Mohanavelu ◽  
Mira Mutnick ◽  
Nidhi Mehra ◽  
Brandon White ◽  
Sparsh Kudrimoti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Chronic Phase ◽  
Molecular Response ◽  
Gastrointestinal Adverse Events

Tyrosine kinase inhibitors (TKIs) are the frontline therapy for BCR-ABL (Ph+) chronic myeloid leukemia (CML). A systematic meta-analysis of 43 peer-reviewed studies with 10,769 CML patients compared the incidence of gastrointestinal adverse events (GI AEs) in a large heterogeneous CML population as a function of TKI type. Incidence and severity of nausea, vomiting, and diarrhea were assessed for imatinib, dasatinib, bosutinib, and nilotinib. Examination of combined TKI average GI AE incidence found diarrhea most prevalent (22.5%), followed by nausea (20.6%), and vomiting (12.9%). Other TKI GI AEs included constipation (9.2%), abdominal pain (7.6%), gastrointestinal hemorrhage (3.5%), and pancreatitis (2.2%). Mean GI AE incidence was significantly different between TKIs (p < 0.001): bosutinib (52.9%), imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). Diarrhea was the most prevalent GI AE with bosutinib (79.2%) and dasatinib (28.1%), whereas nausea was most prevalent with imatinib (33.0%) and nilotinib (13.2%). Incidence of grade 3 or 4 severe GI AEs was ≤3% except severe diarrhea with bosutinib (9.5%). Unsupervised clustering revealed treatment efficacy measured by the complete cytogenetic response, major molecular response, and overall survival is driven most by disease severity, not TKI type. For patients with chronic phase CML without resistance, optimal TKI selection should consider TKI AE profile, comorbidities, and lifestyle.

Sustained molecular response in chronic myeloid leukemia deep responders treated with low dose tyrosine kinase inhibitors

2017 ◽  
Vol 59 (3) ◽  
pp. 766-769 ◽  
Author(s):  
Emilie Cayssials ◽  
Florence Tartarin ◽  
Joëlle Guilhot ◽  
Nathalie Sorel ◽  
Jean Claude Chomel ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Kinase Inhibitors ◽  
Molecular Response

scholarly journals The Role of Monitoring the Bcr-Abl Transcript Levels in the Management of Patients with Chronic Myeloid Leukemia

2013 ◽  
Vol 59 (2) ◽  
pp. 71-74
Author(s):  
Aliz-Beáta Tunyogi ◽  
I Benedek ◽  
Judit Beáta Köpeczi ◽  
Erzsébet Benedek ◽  
Enikő Kakucs ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Chronic Gvhd ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Molecular Monitoring ◽  
Hematopoietic Stem ◽  
Transcript Levels

Abstract Introduction: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder; the molecular hallmark of the disease is the BCR-ABL gene rearrangement, which usually occurs as the result of a reciprocal translocation between chromosomes 9 and 22. Tyrosine kinase inhibitors (TKI) were the first drugs that targeted the constitutively active BCR-ABL kinase and it have become the standard frontline therapy for CML. Monitoring the treatment of CML patients with detection of bcr-abl transcript levels with real time qualitative polymerase chain reaction (RQ-PCR) is essential in evaluating the therapeutic response. Material and method: At the Clinical Hematology and BMT Unit Tîrgu Mureș, between 2008-2011, we performed the molecular monitoring of bcr-abl transcript levels with RQ-PCR in 16 patients diagnosed with CML. Results: We have 11 patients on imatinib treatment who achieved major molecular response. One patient lost the complete molecular response after 5 years of treatment. Two patients in blast crisis underwent allogeneic hematopoietic stem cell transplantation from identical sibling donors. The first patient is in complete molecular remission after 4 years of the transplant with mild chronic GVHD. The other patient had an early relapse with treatment refractory disease and died from evolution of the disease. Three patients with advanced phases of the disease present increasing transcript levels. We performed the dose escalation, and for two of them the switch to the second generation of TKI. Conclusions: Regular molecular monitoring of individual patients with CML is clearly desirable. It allows for a reassessment of the therapeutic strategy in cases of rising levels of BCR-ABL as an early indication of loss of response.

Chronic Myeloid Leukemia: What Every Practitioner Needs to Know in 2017

2017 ◽  
pp. 468-479
Author(s):  
Hanna Jean Khoury ◽  
Loretta A. Williams ◽  
Ehab Atallah ◽  
Rüdiger Hehlmann
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Quantitative Polymerase Chain Reaction ◽  
Chronic Phase ◽  
Safety Net ◽  
Patient Reported Outcome ◽  
Patient Reported ◽  
Treatment Free Remission ◽  
Pro Tools

The prognosis of chronic phase chronic myeloid leukemia (CML) has improved so that life expectancy for patients responding to tyrosine kinase inhibitors (TKIs) is now equivalent to age-matched controls. Attention should be paid to comorbidities that impact survival. The success of TKI therapy can be easily and reliably assessed at well-accepted time points using quantitative polymerase chain reaction (PCR) standardized to the international scale. Patient-reported outcome (PRO) tools are readily available for use in the clinic and provide complementary information on the tolerance of TKIs. Effectively managing adverse events of TKIs can improve compliance and quality of life. Discontinuation of TKIs is the next frontier in CML. In select patients with sustained deep molecular remission, a discontinuation of TKI is associated with a durable treatment-free remission in approximately 50%. Patient engagement in their discontinuation can be achieved through a provider multi-team coaching, is complementary to the available guidelines, and may provide an additional safety net so that these discontinuations remain safe when applied in general practices.

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.

Combination Therapy with Tyrosine Kinase Inhibitors and Agents with Different Mechnisms of Actions Is Effective in a Patient with Chronic Myeloid Leukemia Harboring the T315l BCR - ABL1 Mutation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4282-4282
Author(s):  
Fabio P S Santos ◽  
Jorge Cortes ◽  
Charles Koller ◽  
Elias Jabbour
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Combination Therapy ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Specific Inhibitor ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
T315i Mutation

Abstract Abstract 4282 Mutations of BCR-ABL1 have been observed in 50% of patients with chronic myeloid leukemia (CML) who develop resistance to imatinib. The gate-keeper mutation T315I is one of the mutations with universal resistance to imatinib and to the second-generation tyrosine kinase inhibitors (TKI) that are approved for the treatment of patients with imatinib failure. The use of new kinase inhibitors with in vitro activity against T315I mutation as well as other agents with different mechanisms of actions is being evaluated in clinical trials. We report the case of a 57-year old man that was diagnosed with CML in 2003. Patient received initial therapy with standard-dose imatinib that was subsequently increased to 800 mg daily. He did achieve a complete cytogenetic response (CCyR) 9 months post dose escalation. He was followed by RT-PCR for BCR-ABL1.. In May, 2007, the patient BCR-ABL1/ABL1 ratio increased to 16.38 but the patient remained in CCyR. BCR-ABL1 sequencing revealed the T315I mutation in 100% of cells (Figure 1). One month later the patient lost CCyR (5% Philadelphia-positive [Ph+] cells) and the BCR-ABL1/ABL1 ratio was 5.08. The patient was started on the T315I specific inhibitor KW-2449 (100 mg orally twice daily for 14 days, every 3 weeks). Patient had a progressive decline in percentage of cells with the T315I mutation (Figure 1). However, at the same time he had an increase in percentage of Ph+ cells. In September, 2007, three months after starting therapy with KW-2449, patient had no cytogenetic response (80% Ph+ cells, PCR for BCR-ABL1 ratio > 100) and the T315I mutation was undetectable. At that time, a new ABL1 sequencing revealed the F359I mutation (no quantification was done). Patient was maintained on KW-2449 for the next 6 months, without significant improvement in cytogenetic response nor BCR-ABL1 ratio, but the clone with the T315I mutation did not reappear. In February, 2008, the patient lost hematologic response and presented with an elevated white blood cell count of 22×109/L. The F359I mutation was still present. Therapy with KW-2449 was stopped and the patient started dasatinib 100 mg/day and Interferon-a 3,000,000 units. Three months later, the patient acheived CCyR with a BCR-ABL1/ABL1 ratio of 0.05. At the last evaluation, 16 months after the start of dasatinib and interferon combination, the patient was maintaining CCyR and major molecular response. In conclusion, this case illustrates the benefit of the use of combination therapy, mainly TKI and agent with different mechanism of action either sequentially (TKI followed by KW-2449) or concomitantly (TKI + interferon) in eradicating resistant disease with T315I clone. Figure 1 Serial Monitoring of Ph+ Cells, T315I Cells and BCR-ABL1/ABL1 Ratio Figure 1. Serial Monitoring of Ph+ Cells, T315I Cells and BCR-ABL1/ABL1 Ratio Disclosures: Cortes: Novartis: Research Funding. Jabbour:Novartis: Speakers Bureau; Bristol Myers Squibb : Speakers Bureau.

In Vitro Sensitivity to Tyrosine Kinase Inhibitors Is One of Possible Predictive Parameters for Therapy Switch In Patients with Chronic Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2747-2747
Author(s):  
Marketa Zackova ◽  
Tereza Lopotova ◽  
Zuzana Ondrackova ◽  
Hana Klamova ◽  
Jana Moravcova
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Transcript Level ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Therapy Switch

Abstract Abstract 2747 Backround: Tyrosine kinase inhibitors (TKI) are very effective in chronic myeloid leukemia (CML) suppression, however, the problem with development of resistance in some patients exists. It is necessary to find optimal methods for therapy response prediction and for detection of resistance. Many studies on the resistance to imatinib therapy were performed on cell lines or model systems. However, these systems are not fully consistent with CML situation in vivo. Sensitivity to imatinib and its predictivity to molecular response in patients with de novo CML were tested in vitro on patients′ leukocytes by White et al. [Blood 2005; 106: 2520]. They found that IC50 values could be predictive mainly in patients with low Sokal score. Aims: To optimize in vitro method for evaluation of patients′ sensitivity to various TKIs and to test its predictivity for molecular response in therapy and/or after therapy change. Methods: The sensitivity to TKIs: imatinib, nilotinib and dasatinib were studied on leukocytes isolated from CML patients at diagnosis and various responses to treatment. Cell lines were used as controls. Isolated leukocytes/cell lines were cultivated with/without TKIs. Optimization of cultivation was performed on cell lines (ML-2, K562, CML-T2, JURL-MK1) and on leukocytes from CML newly diagnosed patients (15) and healthy donors (6). Various incubation times (4, 24, 48 and 72h) were tested. Concentrations of TKI were used in values near to physiological levels: 2 –3 concentrations for each inhibitor (1uM, 10uM imatinib, 0,5uM and 2uM nilotinib and 1nM, 10nM and 100nM dasatinib). In given time-points the cells were harvested and lysed for protein and mRNA analyses. Sensitivity to TKIs was tested by BCR-ABL kinase inhibition – via Crkl phosphorylation (western blots) and also by WT1 transcript level kinetics [Cilloni et al, Cancer 2004; 101: 979]. Quality of cultivation was tested by apoptosis level (RNA degradation, Annexin staining – Agilent Bioanalyzer 2100). Results: We found 48 h to be the optimal time for in vitro cultivation. This time was long enough to see TKIs dependent changes on protein as well as mRNA level. At this time the intensity of apoptosis was relatively low and did not influence results. The predictive ability of cultivation with TKIs was tested on patients at diagnosis (15), with optimal (5) and suboptimal response (5) and patient with therapy failure (13). The disease state of all patients was further monitored in range from 6 to 21 months (median 12 months) after cultivation. Mostly all of newly diagnosed patients were in vitro sensitive to all three TKIs, 10 of them achieved MMR (median 7 months, range 5 – 16) on imatinib. In patients with resistance to imanitib therapy the good sensitivity to one of 2nd generation TKI on in vitro tests represented the good response to this inhibitor, 4 patients from 10 on dasatinib achieved MMR (within 4 months), the other responded to therapy with continual decrease of BCR-ABL transcript level. Thus, the cultivation test can help with the therapy switch. However, the prognosis of patients with additive chromosomal aberration was poor even if they were sensitive to TKIs in vitro. Only one of 3 patients with 8 trisomy sensitive to dasatinib in vitro achieved MMR at 4th month after starting of dasatinib. Two patients with T315I were not sensitive to any of TKIs in vitro and in vivo, as it was expected. We continue to follow up of all patients. In conclusion, the results from in vitro cultivations of patients′ leukocytes with TKIs can help with the choice of efficient inhibitor for individual patient′s therapy, however, it is necessary to take into consideration the results of cytogenetic analyses of patients and other factors influencing CML. Supported by MZOUHKT2005. Disclosures: No relevant conflicts of interest to declare.

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