Treatment of Chronic Myeloid Leukemia According to Current Guidelines: The Results of the Pilot Prospective Study “Early Induction Therapy and Monitoring”

Shukhov, OA; Туркина, А. Г.; Chelysheva, Ekaterina; Bykova, AV; Петрова, А. Л.; Gusarova, GA; Nemchenko, Irina; Абдуллаев, А О; Обухова, Т Н; Sudarikov, Andrey

doi:10.21320/2500-2139-2019-12-2-194-201

Клиническая онкогематология

2019

DOI: 10.21320/2500-2139-2019-12-2-194-201

|View full text |Cite

Treatment of Chronic Myeloid Leukemia According to Current Guidelines: The Results of the Pilot Prospective Study “Early Induction Therapy and Monitoring”

OA Shukhov¹,

А. Г. Туркина²,

Ekaterina Chelysheva³

et al.

Abstract: Актуальность. В современных клинических рекомендациях по диагностике и лечению хронического миелолейкоза (ХМЛ) определены показания к смене ингибитора тирозинкиназы (ИТК) первой линии при неудаче терапии на различных этапах течения болезни. Цель. Оценить эффективность терапии ХМЛ при выполнении протокола своевременного мониторинга и переключения на другой ИТК. Материалы и методы. Включение пациентов в пилотное проспективное исследование РИТМ проводилось в течение 5 лет. Анализу подвергнуты данные 100 больных Х… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2020

2024

Publication Types

Select...

Article4

Relationship

Self Cite2

Independent2

Authors

Journals

Cited by 4 publications

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Results of various somatic mutations detection in patients with chronic myeloid leukemia

Kuzmina,

Chelysheva,

Biderman

et al. 2024

Onkogematologiâ

View full text Add to dashboard Cite

Background. Somatic mutations in chronic myeloid leukemia (CML) patients are considered as possible factors for the failure of tyrosine kinase inhibitor (TKI) therapy, and the study of their characteristics is of interest.Aim. To evaluate the genetic profile of blood cells in CML patients using nextgeneration sequencing.Materials and methods. Retrospective study was conducted in two groups of patients: group 1 with TKI therapy failure (n = 29) and group 2 with optimal response to TKI therapy (n = 29). The target panel for nextgeneration sequencing included 19 genes: ASXL1, DNMT3A, FLT3, IDH1, IDH2, NPM1, RUNX1, SF3B1, SRSF2, TET2, TP53, U2AF2, KIT, WT1, CEBPA, ZRSR2, JAK2, GATA2, ABL1. In order to assess clonal evolution, additional samples were examined at a retrospective point in time closest to the primary CML diagnosis.Results. In group 1, mutations in 8 genes (including ABL1) were identified in 19/29 (66 %) patients. Excluding ABL1, mutations were identified in 15 (52 %) patients. In 9 (31 %) patients, >1 mutation (2 to 4) was detected. Frequency of genes mutations in group 1: ABL1 in 11 (38 %) patients, ASXL1 in 9 (31 %) patients, DNMT3A in 3 (10 %) patients, RUNX1, CEBPA in 2 patients (7 %), WT1, NPM1, TET2 in 1 patient (3.5 %). In 7 (24 %) patients there was a combination of mutations in ABL1 gene and in another gene; the most frequent combination of mutations in genes: ABL1 + ASXL1 – in 4 patients (14 %). The dynamics of mutant clones in group 1 was evaluated in 21/29 (72 %) patients. In 10/21 (48 %) patients somatic mutations in genes appeared during CML treatment, in 14/21 (67 %) patients previously detected mutations persisted, in 1 (5 %) the mutation disappeared. In group 2, somatic mutations were detected in 2/29 (7 %) patients: in DNMT3A (ariant Allele Frequency (AF) 5 %) and TP53 (AF 9 %) genes – these mutations were not detected at the diagnosis of CML. In one patient ASXL1 mutation (AF 5 %) was detected only at diagnosis, and was not detected subsequently with optimal response to therapy.Conclusion. The presence of somatic gene mutations is associated with a resistant CML course: somatic mutations in genes other than ABL1 were more common in CML patients with TKI therapy failure than in those with optimal response: 52 % vs. 7 % (p ≤0.05). Mutations in ASXL1 (31 %) and DNMT3A (10 %) were the most frequently detected. The frequency of ABL1 and ASXL1 mutations combination amounted to 14 %. uring followup, somatic mutations predominantly persisted or appeared over time in CML patients with TKI therapy resistance.

show abstract

Results of various somatic mutations detection in patients with chronic myeloid leukemia

Kuzmina,

Chelysheva,

Biderman

et al. 2024

Onkogematologiâ

View full text Add to dashboard Cite

show abstract

Промежуточные Результаты Российского Проспективного Многоцентрового Клинического Исследования READIT-2020 (Снижение Дозы Ингибиторов Тирозинкиназ При ХМЛ, Концентрация Иматиниба/Нилотиниба В Плазме, Сохранение Молекулярного Ответа, Лекарственная Токсичность)

Гурьянова,

Казей,

Шухов

et al. 2024

Clinical Oncohematology

View full text Add to dashboard Cite

AIM. To measure the trough and maximum plasma concentrations of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) patients on standard and reduced doses of the drugs, to evaluate the impact of TKI plasma concentration on the loss of major/deep molecular response (MR) after dose reduction and the impact of TKI plasma concentration on drug toxicity changes. MATERIALS & METHODS. The trial enrolled 46 imatinib and 16 nilotinib recipients. The trough (Сtrough) and maximum (Cmax) TKI plasma concentrations were measured. On imatinib/nilotinib therapy, Ctrough was analyzed in 104/22 and Cmax was analyzed in 63/15 plasma samples, respectively. RESULTS. The mean plasma imatinib Ctrough values on daily 400 mg, 300 mg, and 200 mg of the drug were 1092 ± 346 ng/mL, 809.5 ± 313.0 ng/mL, and 570.9 ± 280.0 ng/mL, respectively. The mean plasma imatinib Cmax on daily 300 mg and 200 mg were 1944 ± 577 ng/mL and 1233.4 ± 44.0 ng/mL, respectively. In the group of patients without deep MR-loss, on daily 300 mg and 200 mg imatinib, the mean plasma Ctrough values were 773.5 ± 303.0 ng/mL and 586.3 ± 308.0 ng/mL, and the mean Cmax values were 1866.5 ± 532.0 ng/mL and 1283.7 ± 481.0 ng/mL, respectively. In the group of patients with deep MR-loss, on daily 300 mg and 200 mg imatinib, the mean plasma Ctrough values were 774.8 ± 553.0 ng/mL and 490.6 ± 175.0 ng/mL, and the mean Cmax values were 2246 ± 1171 ng/mL and 1124.7 ± 281.0 ng/mL, respectively (p > 0.05). The mean plasma imatinib Ctrough values on daily 400 mg, 300 mg, and 200 mg of the drug in the group of patients with drug toxicity were 1120.6 ± 303.0 ng/mL, whereas in the group without adverse effects these values were 998.4 ± 402.0 ng/mL (p = 0.09). The mean nilotinib Ctrough values on daily 600 mg, 400 mg, and 200 mg were 651.4 ± 397.0 ng/mL, 468.7 ± 220.0 ng/mL, and 376.7 ± 151.0 ng/mL, respectively. The mean nilotinib Cmax values on daily 400 mg and 200 mg were 655.3 ± 189.0 ng/mL and 628 ± 293 ng/mL, respectively. CONCLUSION. This clinical trial yielded differences in plasma imatinib Ctrough and Cmax values in CML patients treated with standard and reduced doses of the drug, which turned out to be significant (p < 0.05). No significant differences in plasma nilotinib Ctrough and Cmax were identified. This trial revealed no significant differences in plasma imatinib Ctrough and Cmax on daily 400 mg and 300 mg of the drug in the groups of patients with and without adverse events. However, while dividing plasma imatinib Ctrough values during the period of 400 mg per day administration into 4 quartiles (Q1 and Q4 included patients with the lowest and the highest Ctrough values, respectively), the proportion of patients with drug toxicity appeared to be the highest in Q4 and accounted for 90 %.

show abstract

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

Gurianova¹,

Chelysheva²,

Shukhov³

et al. 2020

Terapevticheskii arkhiv

Self Cite

View full text Add to dashboard Cite

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.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Treatment of Chronic Myeloid Leukemia According to Current Guidelines: The Results of the Pilot Prospective Study “Early Induction Therapy and Monitoring”

Cited by 4 publications

References 23 publications

Results of various somatic mutations detection in patients with chronic myeloid leukemia

Results of various somatic mutations detection in patients with chronic myeloid leukemia

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

Contact Info

Product

Resources

About