Search

Per WHO 2016 and 2022 (5th ed.) myeloproliferative disease guidelines, Chronic Myeloid Leukemia (CML) is classified under two major groups according to the presence of bcr-abl translocation; these groups require different treatment approaches and show clinical presentation heterogeneity. Treatment agents such as tyrosine kinase inhibitors (Imatinib, Dasatinib, Nilotinib, Bosutinib, Ponatinib, Radotinib), Omacetaxine and Asciminib have been used in the treatment of Bcr abl positive CML according to the patient's clinic and mutation status. According to the IRIS study, a study evaluating CML patients treatment response to imatinib, the major molecular response was 33.3% at 3 months, the major molecular response was 48% at 6 months, and the major molecular response was 62.1% at 12 months; furthermore, the rate of achieving a complete molecular response at 12 months was 94.9% (4). In patients who was treated with imatinib as first line therapy, the rate of transformation to accelerated or blastic phase at 18 months was 0.9% in the MMR group and 9.9% in the non-MMR group. In "conventional" CML patients, high leukocyte counts may be accompanied by thrombocytosis; though presentation with only thrombocytosis without leukocytosis is hardly described so far. In this poster presentation, we introduced 7 cases who initially presented with isolated thrombocytosis and then diagnosed with Ph(+) CML. This study was conducted in three adult hematology centers from Antalya, Izmir and Istanbul. 400 patients followed in these centers were reviewed retrospectively; seven patients presented with isolated thrombocytosis were identified. Demographic characteristics, diagnostic findings, and risk scores of these patients were evaluated (Tablo 1). Eln 2013 response criteria were used for evaluation of response for 3rd, 6th, 12th. monthly responses (Figure 1). Here we present 7 CML patients without leukocytosis who were diagnosed with marked thrombocytosis. The patients had similar symptoms and physical examination with no obvious splenomegaly or thrombosis. All of the patients had minimal basophilia and normal peripheral smear findings. All patients responded well to imatinib therapy. During follow up patients who maintained their MMR achieve had a better clinical course and prognosis compared to other CML patients.

Introduction The therapeutic landscape of chronic myeloid leukemia (CML) has evolved significantly since the introduction of imatinib. The European LeukemiaNet (ELN) recommendations serve as a guide for diagnosis, treatment, and monitorization of CML, but availability and accessibility of diagnostic tools and medications affect their applicability. Areas covered This article provides an overview of the current clinical management of CML in Turkey with reference to the key outputs of the online expert meeting held in November 2020. The applicability of the ELN 2020 recommendations for treating CML in clinical practice was also discussed. Expert opinion Imatinib is the only reimbursed and the most preferred first-line treatment in CML restricting the upfront use of second-generation tyrosine kinase inhibitors (TKIs), thereby limiting the applicability of treatment-free remission approach in Turkey. The ELN recommendations about using the EUTOS Long-Term Survival (ELTS) score for risk assessment and focusing on patient reported outcomes and quality of life can be enhanced with educational activities. The widespread availability of standardized technical infrastructure for diagnosing and monitoring CML will contribute to better disease management. Establishing a sustainable national database for CML is valuable for observing patient characteristics and disease outcomes as well as the impact of treatment patterns over time., Novartis Pharmaceuticals Corporation, The study was funded by Novartis Pharmaceuticals Corporation.

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associatedwith gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission.

Background Chronic myeloid leukaemia (CML) is very rare in children. The aim of the study is to report the experience within the I-CML-Ped study in children and adolescents presenting at diagnosis with advanced phase disease and to describe their characteristics and outcomes. Methods Of 479 children and adolescents enrolled in the international registry for childhood chronic myeloid leukaemia (I-CML-Ped Study; www.clinicaltrials.gov NCT01281735 ), 36 children (7.5%) presented at initial diagnosis with CML in advanced phase according to the European LeukemiaNet criteria. Results Nineteen (4%) patients were diagnosed in accelerated phase (CML-AP), and among the 17 patients (3.5%) diagnosed in blastic phase (CML-BP), 70% presented with lymphoid immunophenotype. Initial treatment of CML-AP/CML-BP consisted of tyrosine kinase inhibitors (TKIs) with or without chemotherapy, leading to complete haematologic response in 33 of 36 (92%) patients. Seventeen patients proceeded to haematopoietic stem cell transplantation. At the last follow-up, 18 of 19 patients with de novo CML-AP are alive in at least major molecular response (MMR) (n = 16), in progression (n = 1) or in molecular relapse (n = 1) and 13 of 17 patients with de novo CML-BP are alive in at least MMR. Five-year overall survival rates are 94% (95% confidence interval [CI]: 66%–99%) and 74% (95% CI: 44%–89%) for patients diagnosed in CML-AP and CML-BP, respectively. Conclusion Children with advanced phase at diagnosis of CML seem to have a better survival rate than that reported for advanced phases evolving under TKI treatment.

Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I. The pivotal phase 2 Ponatinib Ph+ ALL and CML Evaluation (PACE) trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) resistant/intolerant to dasatinib or nilotinib, or with BCR-ABL1T315I. This analysis focuses on chronic-phase CML (CP-CML) patients (n = 270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and 4.5-log molecular response, respectively. The probability of maintaining MCyR for 5 years was 82% among responders. Dose reductions were implemented in October 2013 to decrease the risk of arterial occlusive events (AOEs); ≥90% of CP-CML patients who had achieved MCyR or MMR maintained response 40 months after elective dose reductions. Estimated 5-year overall survival was 73%. In CP-CML patients, the most common treatment-emergent adverse events were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%). The cumulative incidence of AOEs in CP-CML patients increased over time to 31%, while the exposure-adjusted incidence of new AOEs (15.8 and 4.9 per 100 patient-years in years 1 and 5, respectively) did not increase over time. These final PACE results demonstrate ponatinib provides durable and clinically meaningful responses, irrespective of dose reductions, in this population of heavily pretreated CP-CML patients. This trial was registered at www.clinicaltrials.gov as #NCT01207440.

We report here on the long-term efficacy of imatinib dose escalation in 74 patients after failure to imatinib conventional dose (13 with hematologic failure and 57 patients with cytogenetic resistance) or suboptimal response (four patients for cytogenetic or molecular). Fifty-four patients received imatinib dose escalation from 400 to 600 mg and 20 patients to 800 mg. A major cytogenetic response was achieved in 41 patients (72%) who escalated imatinib dose for cytogenetic failure and in six patients (46%) with hematologic failure (P = 0.002). Complete cytogenetic response (CCyR) was achieved in 27 (37%) patients: 38% of the hematological failure patients and 42% of the cytogenetic resistant patients (P = 0.345). Cytogenetic suboptimal response patients obtained complete molecular response, whereas the patient, who escalated the dose for molecular suboptimal response at 18 months, did not obtain improvement. After 3 years of follow-up all responding patients are in sustained CCyR. The estimated 2-year PFS and OS is 87% and 85%, respectively. In conclusion, imatinib dose escalation appears to induce sustained responses in CML patients with cytogenetic resistance, in particular in those with acquired resistance. In hematological failure patients, a rapid switch to second generation TKI is instead recommended.

Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph+ CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.