scholarly journals Krónikus myeloid leukaemiás betegek követése a Marosvásárhelyi Hematológiai és Csontvelő-átültetési Klinika beteganyagában 2008 és 2018 között

2019 ◽  
Vol 160 (2) ◽  
pp. 67-72
Author(s):  
Aliz-Beáta Tunyogi ◽  
Erzsébet Lázár ◽  
István Benedek jr. ◽  
Johanna Sándor-Kéri ◽  
Annamária Zsigmond ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Cumulative Probability ◽  
Close Monitoring ◽  
Molecular Remission ◽  
Risk Patients ◽  
Sokal Score

Abstract: Introduction and aim: Chronic myeloid leukemia is a clonal myeloproliferative disorder characterized by the BCR-ABL gene rearrangement with translocation between chromosomes 9 and 22. The constitutively active BCR-ABL tyrosine kinase inhibitor became the standard frontline therapy. The molecular monitoring is essential. Method: We studied the chronic myeloid leukemia patients at the Clinical Hematology and Bone Marrow Transplant Unit Tg-Mures between 2008 and 2018. Results: We followed 59 patients, median age of 45 years, female : male ratio 1.5 : 1. 80% of the patients were in chronic phase. Sokal score was low in 61%, intermediate 27% and high in 12% of the patients. The median follow-up time was 5 years and 9 months. 59% of the patients reached molecular remission (average time 11 months). The cumulative overall survival was 80% at 5 years and 76% at 10 years. The overall survival according to disease phase was 98%, 85%, 20%; according to Sokal score it was 91%, 66%, 51%. The cumulative progression-free survival was 75% at 5 years and 50% at 10 years. Only 8% of the low risk patients are progressing opposite to 77% of the high risk patients. The cumulative probability to maintain the molecular remission for 5 years is 100%, for 10 years 91% and for 15 years 52%. Conclusion: A rising level of BCR-ABL is an early indication of the loss of response identifying the patients who need close monitoring and therapeutic change. Orv Hetil. 2019; 160(2): 67–72.

scholarly journals The Use of Statin Enhances Chance of Achieving MR4.5 in Chronic Myeloid Leukemia Patients in Chronic Phase Following Imatinib Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1804-1804 ◽  
Author(s):  
Dennis Dong Hwan Kim ◽  
Feras Alfraih ◽  
Honggi Lee ◽  
Jeffrey H. Lipton
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Treatment Failure ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Molecular Response ◽  
Statin Group ◽  
Tki Discontinuation

Abstract BACKGROUND: HMG-CoA reducatase inhibitors, or statins, are commonly prescribed medications which improve life expectancy in general population. They are known to improve hypercholesterolemia and decrease the incidence of cardiovascular events including myocardial infarction or stroke, but also suggested for cancer prevention even though the mechanism is not fully elucidated. Recent studies emphasized the potential role of statins in the cancer treatment to increase response rate to chemotherapy and to improve survival of cancer patients. Statin family of drugs is known to trigger tumor specific apoptosis and to result in growth arrest in leukemias (Penn, Leukemia 2002). The promising result of STIM (STop Imatinb) trial suggested that successful discontinuation of tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML) is possible when patients attain deeper molecular response (defined as 4.5 log reduction or deeper) for 2 years or longer. However, with our current knowledge, there is no known additive intervention facilitates the achievement of MR4.5. We hypothesized that the use of statin improves response rate to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML), thus increasing MR4.5 achievement and increasing the chance of being attempted TKI discontinuation. METHODS: A total of 503 patients treated with TKI for CML treatment were initially evaluated for the response to TKI therapy with respect to complete cytogenetic response (CCyR), major molecular response (MMR) and molecular response at 4.5 (MR4.5) and statin use. The inclusion criteria confined the patients with chronic phase (CP) treated with imatinib at the dose of 400mg daily, thus excluding 95 patients. Finally, 408 patients were entered into the final analysis. The statin group was defined as those on statin for cholesterol control at the time of imatinib commencement and remaining on statin while on at least 3 years or longer. Cumulative incidence method considering competing risk was adopted to calculate the incidences of MCyR, CCyR, MMR and MR4.5. Discontinuation of imatinib was accounted as competing risk in the analysis. Treatment failure, progression free- and overall survival was also evaluated. RESULTS: With a median follow-up duration of 6 years (range 3 months to 14 years), 88 patients (21.3%) were defined as “statin” group. Types of statin includes atorvastatin (n=44, 50%), rosuvastatin (n=26, 30%), simvastatin (n=10, 11%), pravastatin (n=6, 7%) and fluvastatin (n=2, 2%). The MCyR and CCyR achievement was not significantly different between the 2 groups (p=0.769 for MCyR and p=0.091 for CCyR). No difference of CCyR at 12 months was noted: 70.1% in statin vs 62.8% in non-statin group. The statin group showed a higher response rate than non-statin group for MMR (p=0.005) and MR4.5 (p=0.001): 67.3% vs 49.2% for MMR at 18 months; 55.8% vs 41.0% for MR4.5 at 5 years (Figure). Multivariate analysis was successful to confirm the use of statin as an independent clinical factor for improving MR4.5 (HR 1.785, 95% CI [1.260-2.530], p=0.001), but other clinical factors were not identified such as Sokal risk, age, gender or additional cytogenetic abnormalities (ACAs) at presentation. For MMR, the use of statin was also confirmed as independent factor for MMR (HR 1.541 95% [1.015-2.341], p=0.043) in addition to ACAs (HR 0.381, p=0.0038) and high sokal risk (HR 0.687, p=0.042). The use of statin was not found to be associated with improvement in treatment failure (p=0.580), progression free survival (p=0.731) or overall survival (p=0.542) in the present study. CONCLUSION: The use of statin suggested to improve deeper molecular response following imatinib therapy in CML-CP patients, therefore is promising to increase chance of attempt to TKI discontinuation. Statin appears to improve the chance of MR4.5 achievement by 78.5%. Careful interpretation is required and replication study in an independent cohort is strongly warranted to reach a clear conclusion on this promising effect of statin. The use of statin to deepen the molecular response of TKI therapy should be evaluated in the context of clinical trial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Changes in the dynamics of the excess mortality rate in chronic phase-chronic myeloid leukemia over 1990-2007: a population study

Blood ◽  
2011 ◽  
Vol 118 (16) ◽  
pp. 4331-4337 ◽  
Author(s):  
Selim Corm ◽  
Laurent Roche ◽  
Jean-Baptiste Micol ◽  
Valérie Coiteux ◽  
Nadine Bossard ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Myeloid Leukemia ◽  
Mortality Rate ◽  
Myeloid Leukemia ◽  
Excess Mortality ◽  
Chronic Phase ◽  
Relative Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
Sokal Score

Abstract Imatinib has transformed the prognosis and the management of chronic myeloid leukemia (CML) and has probably changed the patterns of mortality rates. We explored this change at each disease severity level (Sokal score) through a flexible statistical modeling of the effect of the year of diagnosis on the excess mortality rate. The study included 691 chronic-phase patients from Nord-Pas-de-Calais French CML registry diagnosed from 1990 to 2007. Imatinib was given to 93% of the patients diagnosed after 2000. Comparing the 1990-1994, 1995-1999, and 2000-2007 periods of diagnosis, the 5-year relative survival improved from 64% to 66% and 88%. The year of diagnosis was associated with a significant reduction of the excess mortality, but only in patients with intermediate to high Sokal scores. In high-risk patients diagnosed in the early 1990s, a peak of excess mortality was observed during the second year of follow-up. That peak decreased progressively over the years of diagnosis until disappearing in patients diagnosed after 2000. This study showed different effects according to Sokal scores of the use of imatinib on mortality in patients with chronic-phase CML and showed that since 2000 the pattern of mortality of high-risk patients became similar to that of intermediate-risk ones.

scholarly journals Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3403-3412 ◽  
Author(s):  
H. Jean Khoury ◽  
Jorge E. Cortes ◽  
Hagop M. Kantarjian ◽  
Carlo Gambacorti-Passerini ◽  
Michele Baccarani ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Cytogenetic Response ◽  
Abl Tyrosine Kinase ◽  
Kaplan Meier

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier–estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.

scholarly journals Tyrosine kinase inhibitor–induced platelet dysfunction in patients with chronic myeloid leukemia

Blood ◽  
2009 ◽  
Vol 114 (2) ◽  
pp. 261-263 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
Xin Han ◽  
Hagop Kantarjian ◽  
Jorge Cortes
Keyword(s):  
Platelet Aggregation ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Platelet Dysfunction ◽  
Normal Platelet ◽  
Closure Time ◽  
Platelet Aggregometry ◽  
Increased Risk

Abstract Dasatinib is associated with increased risk of bleeding among patients with chronic myeloid leukemia, even in the absence of thrombocytopenia, suggesting the presence of a hemostatic defect. We tested platelet aggregation in 91 patients with chronic myeloid leukemia in chronic phase either off-therapy (n = 4) or receiving dasatinib (n = 27), bosutinib (n = 32), imatinib (n = 19), or nilotinib (n = 9). All but 3 patients simultaneously receiving imatinib and warfarin had normal coagulation studies. All 4 patients off therapy had normal platelet aggregation. Impaired platelet aggregation on stimulation with arachidonic acid, epinephrine, or both was observed in 70%, 85%, and 59% of patients on dasatinib, respectively. Eighty-five percent of patients on bosutinib, 100% on nilotinib, and 33% on imatinib had normal platelet aggregation. Dasatinib 400 nM induced rapid and marked prolongation of closure time to collagen/epinephrine in normal whole blood on the PFA-100 system. In conclusion, dasatinib and, to some extent, imatinib produce abnormalities in platelet aggregometry testing.

scholarly journals Chronic myeloid leukemia: successful therapy with nilotinib in a young patient with high Sokal risk and in sub-optimal response with imatinib

2015 ◽  
Vol 4 (6S) ◽  
pp. 13-16
Author(s):  
Fausto Palmieri
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Young Patient ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitor ◽  
Standard Dose ◽  
Chronic Phase ◽  
Molecular Response ◽  
Optimal Response ◽  
Increased Risk

Here we describe a case of a young patient with chronic myeloid leukemia, at high-risk according to the Sokal index, who started imatinib at standard dose and obtained a sub-optimal response at 12 months. This condition was not automatically an indication to change therapy, but considering the patient as suboptimal, we decided to switch to a second-generation tyrosine kinase inhibitor (TKI), nilotinib 800 mg/die, obtaining soon a complete cytogenetic response (CCYR), thereafter a major molecular response (MMolR). Delayed achievement of cytogenetic and molecular is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving imatinib therapy. Therefore we can hypothesise that this kind of patient could be elegible for an early switch to second-generation TKI.

Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients

2020 ◽  
Vol 17 (1) ◽  
pp. 48-54
Author(s):  
Reni Widyastuti ◽  
Melva Louisa ◽  
Ikhwan Rinaldi ◽  
Riki Nova ◽  
Instiaty Instiaty ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Cross Sectional ◽  
Imatinib Resistance

Background: Imatinib mesylate is the first tyrosine kinase inhibitor approved for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However, previous studies have shown that about 20-30% of patients eventually would develop resistance to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL kinase domain mutation. One of the most common and serious variations account for imatinib response is T315I of ABL1 gene. Objective: The study aimed to examine the association of T315I mutation with the ABL1 gene and its relation to major molecular response (MMR) achievement in CML patients. This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different possible variations in the ABL1 gene. Methods: This was a cross-sectional study on Indonesian CML patients in chronic phase. We analyzed 120 blood samples from patients in chronic phase who have received imatinib mesylate (IM) for ≥12 months. Results: There were no T315I, F311I, and F317L mutations found in this study. However, we found another variation, which was 36 substitutions from A to G at position 163816 of ABL1 gene (according to NG_012034.1). Conclusions: We found no T315I, F311I, and F317L mutations in this study. Our findings suggest that there might be other factors that influenced the MMR achievement in our study patients. However, there were 36 substitutions from A to G at position 163.816 (according to NG_012034.1) that needed further examination to explore the significance of this mutation in clinical practice.

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