Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin

Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population-based and out-study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20-29% blasts, the hazard ratio (HR) was 1.32 (95%-confidence interval (CI): [0.7-2.6]). Patients with 20-29% blasts had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%-CI: [1.2-4.0], P = .008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs non-high risk) with an HR of 3.01 (95%-CI: [1.81-5.00], P <.001). Regarding the contrasting definitions of blast crisis, our data clearly supported the 20% cut-off over the 30% cut-off in this cohort. Based on our results, we conclude that a one-phase rather than a two-phase categorization of de novo advanced phase CML patients is appropriate.Peer reviewe

Efficacy and safety of tyrosine kinase inhibitors (dasatinib, nilotinib) in the treatment of chronic phase chronic myeloid leukemia

Current treatment options for chronic myeloid leukemia (CML) with imatinib allowed achieving long-term progression-free and overall survival and improved patient quality of life. In cases of imatinib resistance therapy with second-generation tyrosine kinases inhibitors – dasatinib and nilotinib – is also possible. The article represents a literature review evaluating efficacy and toxicity of both drugs and highlighting some of the practical issues of CML treatment after first-line therapy failure.</p

Change of concentration of biochemical markers of dysfunction of endothelium at intake of inhibitors of tyrosinekinase of I and II generations at patients with a chronic myeloid leukemia as risk factor of development of cardiovascular complications

CML), the accepting inhibitors tyrosine of kinases (TKI) I and the II generations (TKI1 and TKI2 respectively), and development of arterial hypertension.Material and methods. Examination of 137 patients with CML in the chronic phase (CP) is conducted, the median of age — 47 years. 24 of them were with for the first time the verified diagnosis of CML and earlier did not accept TKI, they have made group of control. Other patients accepted TKI: 39 patients — imatinib 400 mg/day, 36 — dasatinib 100 mg/day, 38 — nilotinib 800 mg/day) more than 6 months. In biochemical analysis of blood indicators of lipidic range were defined. Level detection of ET-1 and VEGF was made by means of enzyme immunoassay. To all patients measurement of the heart rate (HR) and the arterial blood pressure (ABP) on both hands at an interval of 2 minutes from previous was once taken.Results. In group of patients from CML accepting nilotinib authentically significant increase in levels of systolic and diastolic ABP (р&lt;0,001) in comparison with group of control, with group of the patients accepting imatinib and dasatinib is noted. The most serious changes of lipidic range are noted at the patients accepting nilotinib. In all groups statistically significant increase in level of C-reactive protein, fibrinogen, homocysteine, endothelin-1 and VEGF in comparison with group of control is revealed. The most expressed changes are found in group of the patients accepting nilotinib, values of parameters of C-reactive protein, fibrinogen, homocysteine, endothelin-1 and VEGF are changed authentically (р&lt;0,001) and statistically significantly differ in comparison with group for the first time of the revealed patients with CML and groups of reception of imatinib and dazatinib.Conclusion. As a result of the conducted research endothelium variation of a function at patients from CML accepting TKI1 and TKI2 is revealed. The above-stated indicators can be used as additional diagnostic criteria for assessment of risk of development of arterial hypertension in patients with CML at reception of TKI

Quality of life, symptom profile and clinical efficacy of second-line treatment with dasatinib in patients with imatinib-resistant or -intolerant chronic myeloid leukemia: results of 2-year follow-up

The article is focused on the results of the multicenter observational study “Quality of life and symptom profile in patients with chronic myeloid leukemia in chronic phase in long-term follow-up of second-line treatment” (2012–2015). Thirty imatinib-resistant or-intolerant patients with chronic myeloid leukemia in chronic phase were observed in the real-world clinical setting during 24 months after start of second-line treatment with dasatinib. Mean age – 48 years old (SD = 13.1); males / females – 14 / 16; one third of patients were with comorbidity, Charlson Index – 0–5 scores. All the patients received dasatinib in the dosage of 100 mg daily. Study time points – 12, 18 and 24 months after second-line treatment start. Treatment outcomes were analyzed in terms of clinical efficacy and safety as well as in terms of patient-reported outcomes, including quality of life and symptom profile assessment. For quality of life and symptom assessment the SF-36 and CSP-CML questionnaires were used, respectively. Statisticallly significant changes in quality of life and symptom severity were analyzed by generalized estimated equation (GEE). Complete hematological response was observed in 96.3 % patients, complete cytogenetic response – in 66.6 % patients, complete or major molecular response – in 60 % patients. The acceptable tolerability of dasatinib treatment was shown during long-term follow-up: hematological and non-hematological serious adverse events were rare and didn’t lead to treatment discontinuation. Significant improvement of physical functioning, role physical functioning, role emotional functioning, vitality and mental health as compared to base-line parameters was observed (p &lt; 0.05). The severity of a number pronounced symptoms decreased and the proportion of patients with severe symptoms reduced (p = 0.01) after 24 months of second-line treatment start. Quality of life treatment response in terms of stabilization or improvement was registered in 83 % of patients. The data of this real-world study in CML patients are in line with the results of clinical studies in terms of dasatinib treatment efficacy and safety. In addition, they demonstrate the value of patient-reported outcomes to evaluate benefits and risks of long-term dasatinib treatment from patient perspective

CLINICAL AND LABORATORY FEATURES OF ESSENTIAL THROMBOCYTOSIS AND PRIMARY MYELOFIBROSIS DEPENDING ON JAK2 AND CALR1 MUTATION STATUS

Introduction. JAK2V617F mutation is detected in approximately 50 % of patients with essential thrombocytosis (ET) and primary myelofibrosis (PMF). In 2013 most of the JAK2 negative patients showed mutations in the CALR gene. Diagnostic value of JAK2 and CALR mutations is high, but their prognostic significance is not sufficiently clear. Data on impact of JAK2 and CALR mutational status on thrombotic complications in ET and myelofibrosis patients are contradictory.The aim of the study was to identify clinical and laboratory features in patients with ET and PMF in accordance with the mutational status of JAK2V617F and CALR gene.Materials and methods. Patients treated in Almazov National Medical Research Center (St. Petersburg), Chuvash Republican Clinical Hospital (Cheboksary), Irkutsk Regional Clinical Hospital (Irkutsk),  Kirov Research Institute of Hematology and Blood Transfusion (Kirov) was included in the retrospective study. CALR mutation (1 and 2 types), MPL W515L/K and JAK2V617F mutation were detected in peripheral blood cells.Results. We identified that 21 % (n = 16) of ET patients had thrombotic complications, and they occurred more often among JAK2V617F positive patients (p &lt;0.05). The median of hemoglobin level in PMF was the lowest in the group of triple negative patients. The level of leukocytes in PMF was higher in the group of triple negative patients than in the group with mutated CALR (p = 0.014).Conclusion. JAK2V617F mutation in ET patients was associated with a high risk of thrombosis. Patients with CALR mutations may have a favorable prognosis regarding to thrombotic complications. Some laboratory features of CALR mutations in ET and PMF patients have been revealed

First-line treatment selection and early monitoring patterns in chronic phase-chronic myeloid leukemia in routine clinical practice : SIMPLICITY

Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1242 prospective patients (enrolled October 01 2010-September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift toward dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P &lt; .001) and at academic versus community practices (P = .001). Age &lt;65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first-line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long-term patient outcomes are likely to be impacted

CML-047 Post Hoc Analysis of Responses to Ponatinib in Patients With Chronic-Phase Chronic Myeloid Leukemia (CP-CML) by Baseline BCR::ABL1 Level and Baseline Mutation Status in the OPTIC Trial

International audienceObjectives: OPTIC (NCT02467270) is a Phase 2 trial evaluating the safety and efficacy of ponatinib in patients with CP-CML resistant to ≥2 TKIs or have a T315I mutation. We present a post hoc analysis of patient responses by baseline BCR::ABL1 level and mutation status. Methods: Patients with CP-CML resistant to ≥2 TKIs or with the T315I mutation were randomized to ponatinib starting doses of 45 mg, 30 mg, and 15 mg once daily. Doses were reduced to 15 mg after achievement of ≤1% BCR::ABL1IS in the 45-mg and 30-mg cohorts. The primary endpoint is ≤1% BCR::ABL1IS at 12 months. In this analysis, outcomes are analyzed by baseline T315I mutation status and baseline BCR::ABL1 level in the intent-to-treat (ITT) population. Results: 283 patients were randomized (45-mg/30-mg/15-mg cohorts: n=94/95/94). At baseline, 84.1% of patients had &gt;10% BCR::ABL1IS; 23.8% had T315I mutation. Subanalysis showed that patients with T315I mutations in the 45-mg cohort had the highest ≤1% BCR::ABL1IS response rates (60%) by 3 years versus other cohorts. Across cohorts, 97 patients without T315I mutations achieved ≤1% BCR::ABL1IS. Median duration of response (mDoR) for patients with a T315I mutation at baseline was 27 months in the 45-mg cohort (n=15) and 12 months in the 30-mg cohort (n=5). For patients without T315I mutations, the mDoR was not reached. Across cohorts, 79% of patients who achieved ≤1% BCR::ABL1IS maintained this response during the study. The most common nonhematologic treatment-emergent adverse events (TEAEs) and hematological TEAEs in the ITT population for all cohorts combined were arterial hypertension (28%), headache (18%), lipase increase (17%), thrombocytopenia (40%), neutropenia (26%), and anemia (19%). Overall, 6.0% of patients experienced a treatment-emergent arterial occlusive event (TE-AOE); 4.6% experienced a Grade ≥3 TE-AOE. Conclusions: The OPTIC post hoc analysis showed clinical benefit across dosing regimens regardless of T315I mutation status at baseline; the 45-mg cohort showed the highest response rates regardless of baseline BCR::ABL1IS levels. Regardless of T315I mutation status, most patients were able to maintain their response after dose reduction upon achieving BCR::ABL1IS ≤1%. This abstract is an encore from the American Society of Hematology 2021 Annual Meeting