Long-term tolerability and efficacy after initial PegIFN-α addition to dasatinib in CML-CP: Five-year follow-up of the NordCML007 study.

OBJECTIVES: Treatment-free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML-CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon-α in addition to TKI has shown promising efficacy but with dose-dependent toxicity and discontinuations. NordCML007 was initiated to study the efficacy and safety of low dose pegylated IFN-α (PegIFN-α) in combination with dasatinib (DAS) in CML-CP. METHODS: Forty patients with newly diagnosed CML-CP were given DAS upfront. After month 3 (M3) 15 µg/wk of PegIFN-α was added and increased to 25 µg/wk from M7 until M15. DAS treatment was continued and adverse events and BCR-ABL1 qRT-PCR values were reported yearly after M24. Results from M1 to M18 have previously been published, and here we present long-term data. RESULTS: After 5 years of follow-up, there were no suspected unexpected serious adverse reactions, no increase in serosal effusions, no disease progressions and no CML-related deaths. Rates of MR3.0 (MMR), MR4.0 and MR4.5 were 84.6%, 64.1% and 51.3% respectively at M60, and 95% of patients reached MMR at some point during the study. CONCLUSION: Initial addition of PegIFN-α to DAS shows good long-term efficacy without increased toxicity.

Treatment patterns and clinical outcomes of tyrosine kinase inhibitors in chronic-phase CML in clinical practice: 3-year European SIMPLICITY data.

OBJECTIVES: SIMPLICITY (NCT01244750) is an observational study of patients with chronic-phase chronic myeloid leukemia (CP-CML) in routine clinical practice receiving first-line tyrosine kinase inhibitors (TKIs). We evaluated TKI treatment changes and how switching affects clinical response in patients recruited in Europe with ≥3 years of follow-up. METHODS: The SIMPLICITY European cohort (France, Germany, Italy, the Netherlands, Russia, and Spain) included 431 patients. 370 (86%) were followed for ≥3 years. RESULTS: Proportions of patients experiencing treatment interruptions, TKI switching, and discontinuations decreased over 3 years' follow-up. Intolerance was a key driver for treatment changes. Complete cytogenetic response (CCyR) was achieved in 87.5% of patients switching TKI within 3 years of initiation vs 91.7% of non-switchers. Major molecular response (MMR) was achieved in 82.4% of switchers vs 92.9% of non-switchers. Over 3 years, not switching TKI was a strong predictor for achieving CCyR or MMR (both P < .05). Three-year survival remained high, irrespective of treatment changes (95.3% switchers, 96.4% non-switchers). CONCLUSIONS: European patients with CP-CML who do not switch TKI are more likely to achieve clinical response, while intolerance is a key driver for switching. Successful CML management may require careful selection of initial TKI, with early monitoring of response and intolerance.

Tyrosine Kinase Inhibitors in Leukemia and Cardiovascular Events: From Mechanism to Patient Care.

Targeted oncology therapies have revolutionized cancer treatment over the last decade and have resulted in improved prognosis for many patients. This advance has emanated from elucidation of pathways responsible for tumorigenesis followed by targeting of these pathways by specific molecules. Cardiovascular care has become an increasingly critical aspect of patient care in part because patients live longer, but also due to potential associated toxicities from these therapies. Because of the targeted nature of cancer therapies, cardiac and vascular side effects may additionally provide insights into the basic biology of vascular disease. We herein provide the example of tyrosine kinase inhibitors utilized in chronic myelogenous leukemia to illustrate this medical transformation. We describe the vascular considerations for the clinical care of chronic myelogenous leukemia patients as well as the emerging literature on mechanisms of toxicities of the individual tyrosine kinase inhibitors. We additionally postulate that basic insights into toxicities of novel cancer therapies may serve as a new platform for investigation in vascular biology and a new translational research opportunity in vascular medicine.

Keratosis pilaris-like eruption secondary to nilotinib in a child.

Nilotinib is a new multitargeted tyrosine kinase inhibitor, which is used to treat chronic myelogenous leukemia when intolerance or recurrence to imatinib occurs. We report the case of a 14-year-old patient being treated with nilotinib who developed a keratosis pilaris-like eruption. This cutaneous adverse effect is a rare but increasingly reported side effect of this therapy.

Dasatinib dose management for the treatment of chronic myeloid leukemia.

Chronic myeloid leukemia (CML) has evolved into a chronic disease that is managed with tyrosine kinase inhibitor therapy. Now that long-term survival has been achieved in patients with CML, the focus of treatment has shifted to dose optimization, with the goal of maintaining response while improving quality of life. In this review, the authors discuss optimizing the dose of the second-generation tyrosine kinase inhibitor dasatinib. Once-daily dosing regimens for dasatinib in the first and later lines of treatment were established through long-term (5-year and 7-year) trials. Recently published data have indicated that further dose optimization may maintain efficacy while minimizing adverse events. Results obtained from dose optimization and discontinuation trials currently in progress will help practitioners determine the best dose and duration of dasatinib for patients with CML, because treatment decisions will be made through continued discussions between physicians and patients. Cancer 2018;124:1660-72. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

[Chronic myelogenous leukemia: monitoring and predictors of a favorable response to treatment with imatinib]. / Leucemia mieloide crónica. Monitoreo y factores predictivos de una respuesta favorable en el tratamiento con imatinib.

The expected five-year survival of chronic-phase chronic myeloid leukemia patients treated with tyrosine kinase inhibitors is over 90%. Little data is available regarding the results in the Argentinian population. This information might be of interest as generic imatinib is now available in the region. The aim of this study is to provide information on monitoring and the long-term treatment with imatinib outside of a controlled clinical trial, as well as to analyze the predictive effect of early responses to achieve molecular remission 4.0 (RM 4.0) and the detection of variables that may condition treatment failure. We included 106 patients, who received imatinib 400 mg daily as first-line inhibitor for a median of 8.9 years (IQR 5.8-11.7) between June 2000 and December, 2015. Overall survival was 93%. At latest follow-up 74% of patients continues on initial imatinib. The achievement of response at targeted milestones (6, 12 months) was associated with increased failure-free survival: 87% vs. 56%, p = 0.007; 90% vs. 69% p = 0.01 and was independently associated to RM 4.0: OR 5.6 (95% CI: 1.6-19.0); OR 5.3 (95% CI: 1.4-21.0) p = 0.006. After long-term follow-up, imatinib provided high-rates of response and survival. The prognostic value of response at targeted milestones was confirmed. This study reinforces the importance of molecular monitoring under IS standardization at known timepoints and this must continue to be a target in Argentina.

Rapid onset of peripheral artery disease in a chronic myeloid leukemia patient without prior arterial disorder: direct relationship with nilotinib exposure and clinical outcome.

The second-generation tyrosine kinase inhibitor (TKI) of the BCR-ABL1 oncoprotein nilotinib used in patients with chronic myeloid leukemia is suspected to increase the risk of arterial occlusion, especially in patients with pre-existing cardiovascular risk factors or established cardiovascular diseases. Here, we describe a case of unexpected and rapid onset of symptomatic peripheral artery disease (PAD) associated with silent stenosis of digestive and renal arteries in a nilotinib-treated patient devoid of significant cardiovascular diseases (CVD) risk factor, prior atherosclerotic disease, or other cause of arterial damage. This is the first report to establish a direct relationship between nilotinib exposure and PAD and to reveal that arterial damage is irreversible despite rapid drug withdrawal. However, functional outcome was favorable upon rapid TKI replacement, specific cardiovascular disease management, and development of collateral arterial network.

A Case of Hepatocellular Carcinoma after Treatment for Chronic Myeloid Leukemia in a Patient without Liver Disease.

Introduction: Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the reciprocal translocation of chromosomes 9 and 22, which leads to a chimeric gene product known as BCR-ABL. Some studies have shown a higher incidence of secondary malignancies than the one seen in the general population in patients with CML. Hepatocellular carcinoma (HCC) is rarely reported in association with CML and/or CML-related treatment. Case Presentation: We describe a case of a patient with no history of liver disease and CML on imatinib for 10 years, who presented with worsening right upper quadrant abdominal pain. Imaging revealed a large hepatic mass highly suspicious of malignancy that later was confirmed to be HCC after biopsy. The patient was bracketed with advanced stage HCC (BCLC stage C) and given her advanced age and poor performance status; palliative care was offered. Conclusion: Patients with CML have a common association with secondary malignancies. This is the first case report based on our extensive review of available literature that HCC was diagnosed in a patient with CML on treatment with imatinib without any clear or usual underlying cause.

A Case of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in a 26-Year-Old Pregnant Woman.

Acute lymphoblastic leukemia (ALL) is an uncommon and rapidly progressing blood cancer originating in the bone marrow, characterized by the abnormal proliferation of immature lymphocytes. Although most cases of ALL are observed in children, the disease pattern shows two peaks: one in early childhood and another around the age of 50. Approximately a fifth to a third of adults diagnosed with ALL exhibit cytogenetic abnormalities involving the Philadelphia chromosome. Despite the existence of several studies on Philadelphia chromosome-positive ALL (Ph+ ALL), our case accentuates the use of a multi-disciplinary approach to treatment and involves a patient from a unique demographic.

Dasatinib-Induced Bilateral Chylothorax: A Case Report.

Dasatinib, a BCR-ABL tyrosine kinase inhibitor, is used in the management of Philadelphia-positive chronic myeloid leukemia (CML). Several adverse complications of this targeted immunotherapy have been reported. This case report focuses on a 79-year-old female who presented with acute dyspnea and generalized chest pressure while undergoing management with this specific tyrosine kinase inhibitor. Bilateral chylothorax was diagnosed with the aid of imaging, laboratory studies, and diagnostic thoracentesis. No other risk factors, including trauma, lung malignancies, or congenital anomalies, were detected in this patient. Since no other etiologies for the development of chylothorax were identified, it was concluded that dasatinib therapy was the inciting factor. Dasatinib was discontinued and bosutinib was initiated. A low-fat diet was prescribed, which the patient was amenable to. Six months later, the patient remained stable with no recurrence of chylothorax. The mechanism of dasatinib-induced chylothorax is currently under investigation. The purpose of this report is to raise awareness about dasatinib-induced chylothorax, aid in identifying predisposing risk factors, and enhance understanding of the proper management of this rare complication.

Case report: An intriguing case of Philadelphia chromosome-positive acute lymphoblastic leukemia recurrence.

The incorporation of tyrosine kinase inhibitors (TKIs) in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) led to significant improvement. However, in the pediatric setting, the outcomes of Ph+ ALL are still inferior compared to those of other ALL subtypes even in the TKI era due to higher relapse rate. Herein, we report a very peculiar case of late extramedullary Ph+ ALL relapse in a child, characterized by lymphomatous presentation in the tonsils and lymphoid lineage switch. The diagnostic dilemma between the occurrence of a second malignant neoplasm and the recurrence of the primary disease is further discussed, highlighting the importance of molecular backtracking analysis. This case report emphasizes the high plasticity and polyclonal nature of ALL and expands the heterogeneity of possible clinical presentation of Ph+ ALL at relapse.

[Tyrosine kinase inhibitors for chronic myeloid leukemia]. / Inhibiteurs de tyrosine kinase dans la leucémie myéloïde chronique.

TYROSINE KINASE INHIBITORS FOR CHRONIC MYELOID LEUKEMIA. About 20 years ago, the discovery of imatinib, the first ATP-competitive inhibitor of BCR::ABL1 the driving oncoprotein of chronic myeloid leukemia (CML), revolutionized patients' outcome by transforming a fatal condition into a chronic one. Today, five more tyrosin kinase inhobitors (TKIs) have been approved, allowing to some extent individualization of drug therapy. The main therapeutic objective is to protect patients from progression towards a fatal blast crisis and to restore of a near-to-normal life expectancy on lifelong TKI treatment. Only a minority of patients manage to achieve a state called treatment-free remission. Research efforts must go on as some challenges remain such as improving scoring systems, increasing TKI safety profile, fighting against resistance and finding how to cure CML.

INHIBITEURS DE TYROSINE KINASE DANS LA LEUCÉMIE MYÉLOÏDE CHRONIQUE. Il y a un peu plus de vingt ans, l'imatinib, premier inhibiteur compétitif de l'adénosine triphosphate (ATP) ciblant l'oncotyrosine kinase BCR::ABL1, a révolutionné le pronostic de la leucémie myéloïde chronique. Aujourd'hui, cinq autres inhibiteurs ont rejoint la pharmacopée et permettent, dans une certaine mesure, une personnalisation des stratégies thérapeutiques. L'objectif premier de la prise en charge est la protection contre la progression de l'hémopathie vers une forme aiguë fatale et la restauration d'une espérance de vie normale sous traitement à vie ­ une minorité de patients parviennent tout de même à arrêter le traitement. Malgré la richesse de l'arsenal thérapeutique, la recherche doit continuer : des progrès restent nécessaires pour améliorer les systèmes pronostiques existants, augmenter la sécurité d'emploi des inhibiteurs de tyrosine kinase, combattre la multirésistance et la transformation aiguë et parvenir à la rémission sans traitement pour tous les patients.

Pediatric chronic myeloid leukemia in myeloid blast crisis.

Chronic myeloid leukemia (CML) accounts for 2-3% of childhood leukemias. About 5% of cases present in a blastic phase of CML which clinically and morphologically mimics more common acute leukemias of childhood. We report a case of a 3-year-old male who presented with gradual onset swelling of the abdomen and extremities along with generalized weakness. Examination revealed massive splenomegaly, pallor, and pedal edema. Initial workup showed anemia, thrombocytopenia, and leukocytosis (120,000/uL) with a blast percentage of 35%. Blasts were positive for CD13, CD33, CD117, CD34 and HLA-DR, and stained negative for Myeloperoxidase and Periodic Acid Schiff. Fluorescence in situ hybridization was positive for b3a2/e14a2 junction BCR-ABL1 transcript and negative for RUNX1-RUNX1T1/t(8;21), clinching the diagnosis of CML in myeloid blast crisis. The patient expired within 17 days of diagnosis and initiation of therapy.

Philadelphia Chromosome Positive Chronic Myelogenous Leukemia Blastic Crisis in A Patient with Unusual Primary Myelofibrosis Characteristics; A Case Report.

INTRODUCTION: Myeloproliferative neoplasms (MPNs) are divided into BCR-ABL positive Chronic myeloid leukemia (CML) and BCR-ABL negative MPNs including Polycythemia vera (PV), Essential Thrombocythemia (ET) and Primary myelofibrosis (PMF). Evaluation of the Philadelphia chromosome in MPNs is a diagnostic requirement for classic CML. CASE REPORT: In 2020, a 37-year-old woman with negative cytogenetic testing for Janus kinase2 (JAK2), Calreticulin (CALR), myeloproliferative leukemia virus oncogene (MPL), and positive for BCR-ABL1 mutation with reticular fibrosis in bone marrow was diagnosed as CML. Some years ago, the patient had been diagnosed with PMF with evidence of histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD). The BCR-ABL fusion gene was initially evaluated which was negative. Then, Cutaneous squamous cell carcinoma (cSCC) was confirmed by Dermatopathologist with palpable splenomegaly and high white blood cell (WBC) count with basophilia. Finally, BCR-ABL was detected positive by the fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR). In fact, the co-occurrence of PMF with CML was identified. CONCLUSION: This case study highlighted the importance of some cytogenetic methods in the detection and classification of MPNs. It is recommended that physicians pay more attention to it and be aware of the planning treatment.

Medication experience and patient's related needs in chronic myeloid leukemia treated with tyrosine kinase inhibitors: Systematic review. / Necesidades y experiencia farmacoterapéutica de los pacientes con leucemia mieloide crónica tratados con inhibidores de la tirosina cinasa: revisión sistemática.

OBJECTIVE: Several studies quantitatively described patients with Chronic Myeloid Leukaemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukaemia in qualitative research articles published in the scientific literature. METHODS: A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukaemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded. RESULTS: 184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure. CONCLUSIONS: This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukaemia and receiving treatment with tyrosine kinase inhibitors.

Brazilian chronic myeloid leukemia working group recommendations for discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia in clinical practice.

INTRODUCTION: Treatment-free remission (TFR) is a new goal of chronic myeloid leukemia (CML) therapy. TFR is feasible when the patient has achieved a deep and stable molecular response and met the criteria required to ensure its success. Treatment discontinuation should not be proposed to the CML patient if minimum conditions are not met. In Brazil, for example, molecular tests (BCR::ABL1) are not broadly available, making it difficult to monitor the patients adequately. OBJECTIVE: In this sense, providing TFR recommendations for Brazilian physicians are therefore necessary. These recommendations include the main criteria checklist to start the TKIs treatment discontinuing process in patients diagnosed with CML and the population-eligible characteristics for treatment discontinuation. METHOD: Age, risk score at diagnosis, TKI treatment duration, BCR::ABL1 transcripts type, depth of the molecular response for treatment discontinuation, treatment adherence, patient monitoring and withdrawal syndrome are essential factors to consider in TFR. After TKI discontinuation, BCR::ABL1 transcripts monitoring should be more frequent. When a major molecular response loss is observed during the monitoring of a patient in TFR, the TKI treatment should be resumed. CONCLUSION: These recommendations should serve as a basis for medical professionals interested in proposing TKI discontinuation for CML patients in clinical practice. It is important to highlight that, despite the benefits of TFR for the patients and the health system, it should only be feasible following the minimum standards proposed in this recommendation.

COVID-19 in patients with chronic myeloid leukaemia on tyrosine kinase inhibitor therapy: a Honduran observational study.

Introduction: In the earliest cases of COVID-19, a higher percentage of severe and fatal cases was observed in patients with cancer, including those with haematological malignancies. However, patients with chronic myeloid leukaemia (CML) had better prognoses, suggesting that tyrosine kinase inhibitors (TKIs) may have a therapeutic effect against SARS-CoV-2. This study describes the clinical and epidemiological characteristics of patients with CML receiving the TKIs tested for SARS-CoV-2 in Tegucigalpa, Honduras. Methodology: An Analytical cross-sectional study was conducted. The sample included patients with Philadelphia chromosome-positive (Ph+) CML, who had been tested at least once for COVID-19 at the Emma Romero de Callejas Cancer Centre (CCERC). Sociodemographic and clinical variables were both analysed. Epi Info 7.2.4.0 and Stata/MP 16.0 were used to collect and analyse data. The COVID-19 positivity percentage and the association between severity and the TKI used were determined using Fisher's exact test and odds ratio (OR). Data were gathered from clinical records with approval of CCERC institutional management. Results: One hundred and forty-nine patients with Ph+ CML were included; 20.1% were COVID-19-positive; 56% were male; mean age was 46 years; 81% were receiving imatinib, with a mean treatment duration of 6 years; 55% achieved a BCR -ABL molecular response ≤ 0.1% (IS). Twenty-one percent had comorbidities. COVID-19 was asymptomatic in 38.7% of patients, mild in 35.5% and severe in 9.7%. One patient died, a fatality rate of 3.2%. No statistical association was found between disease severity and treatment with imatinib versus second-line TKI (OR: 0.833, p: 0.8493, 95% CI: 0.098-10.998). Conclusion: Despite high COVID-19 positivity in CML when compared with the literature, this study found a lower fatality rate. The type of TKI used or molecular response at the time of infection was not associated with case severity. Determining the effectiveness of imatinib or other TKIs as a COVID-19 treatment requires randomised clinical trials.

Classic myeloproliferative neoplasms in Singapore: A population-based study on incidence, trends, and survival from 1968 to 2017.

BACKGROUND: Current descriptive epidemiological information on classic myeloproliferative neoplasms (MPNs) is incomplete. Published data among Asian population are particularly sparse. METHODS: We conducted a large population-based study to determine the incidence rates and survival patterns of MPN reported to the Singapore Cancer Registry during the period 1968-2017. Age-standardised incidence rates(ASR), overall survival, 5-/10-year relative survival ratio (RSR) were estimated. Joinpoint regression was used to evaluate quinquennial percent change (QPC) in incidence. RESULTS: We identified 2557 individuals diagnosed with MPN including 1031 chronic myeloid leukaemia (CML), 424 polycythaemia vera (PV), 389 essential thrombocythaemia (ET), 134 primary myelofibrosis (PMF) and 579 MPN unclassifiable (MPN-U). The overall respective ASRs per 100,000 for CML, PV, ET, PMF and MPN-U were 1.24, 1.15, 1.07, 0.43, and 0.80 in 2013-2017. Males had higher ASR than females in all MPNs. A gradual rise in incidence trends of CML was observed between 1968 and 2017 (QPC 2.1%, 95% CI -0.9, 5.3). The overall incidence trends of non-CML MPNs including PV (QPC 62.9%, 95% CI 19.3, 122.6), ET (QPC 54.2%, 95% CI 23.5, 92.3) and PMF (QPC 103.5%, 95% CI 19.1, 247.6) increased sharply during 1993-2017. Survival was lower in MPNs compared with expected survival in general population: 5-year RSRs were 0.82 (95% CI 0.78, 0.86), 0.96 (95% CI 0.91, 1.01), 0.96 (95% CI 0.92, 1.01), 0.53 (95% CI 0.43, 0.65), and 0.74 (95% CI 0.68, 0.80) for CML, PV, ET, PMF and MPN-U respectively. CONCLUSION: CML incidence has increased marginally, whereas non-CML MPNs incidences have sharply increased. MPN patients have a lower relative survival compared to the general population, and patients with PV and ET have the most favourable relative survival. Median survival for CML patients has increased dramatically over the last 50 years.

Long-term safety and efficacy of imatinib in pediatric patients with chronic myeloid leukemia: single-center experience from China.

Chronic myeloid leukemia (CML) is a rare disease among children. A retrospective study was conducted from November 2002 to March 2019 at a single institution in China. A total of 36 pediatric CML patients (25 male and 11 female) were enrolled. Median follow-up time was 51 months (range 8-144), and 5-year overall survival and event-free survival were 95.5 ± 4.4% and 88.9 ± 6.0%, respectively. Among the 25 patients whose response to imatinib mesylate (IM) was regularly monitored, 92.0% achieved complete hematologic response at 3 months, 80.0% achieved complete cytogenetic response at 12 months, and 64.0% achieved major molecular response at 18 months after IM therapy. A higher WBC count at diagnosis was associated with failure to achieve early molecular response (EMR). Height standard deviation score after long-term treatment was significantly and positively correlated with age at diagnosis and at the start of IM therapy. Overall, IM therapy was effective in treating pediatric CML, and WBC count at diagnosis might be an ideal predictor of EMR. Moreover, retardation of height and weight growth due to IM tended to affect patients younger than 9 years old at diagnosis, and longitudinal growth might normalize further into treatment.

[Analysis of clinical features and prognosis of patients with chronic myelogenous leukemia harboring additional chromosomal abnormalities in Ph-positive cells].

Objective: To investigate the effects of additional chromosomal abnormalities (ACA) in Philadelphia chromosome-positive (Ph(+)) cells on biological characteristics, therapy efficacy, and prognosis of patients with primary chronic myeloid leukemia (CML) -chronic phase (CP) and those who developed CML-accelerated phase/blast phase (AP/BP) during therapy. Methods: The clinical data of 410 patients with Ph(+) CML, including 348 patients with primary CML-CP and 62 patients who progressed to CML-AP/BP during treatment, who were admitted to Henan People's Hospital from January 2013 to June 2020 were retrospectively analyzed to categorize into high-risk, non-high-risk, and non-ACA groups according to the ELN2020 criteria. The effects of high- and non-high-risk ACA on biological characteristics, therapy efficacy, and prognosis were compared. Results: ①Among the 348 patients with primary CML-CP, 20 patients (5.75% ) had ACA, including 3 and 17 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 328 patients did not have ACA. There were no significant differences in baseline clinical characteristics between those with and without ACA (P>0.05 for all) . The rates of complete hematological response, complete cytogenetic response, major molecular remission, and 5-year overall survival (OS) were not significantly different between the non-high-risk ACA and non-ACA groups (P>0.05 for all) ; however, the 5-year progression-free survival of the non-high-risk ACA group (42.0% ) was significantly lower than that of the non-ACA group (74.5% ) (χ(2)=4.766, P=0.029) .②Of the 62 patients who progressed to CML-AP/BP during treatment, 41 patients (66.13% ) had ACA, including 28 and 13 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 21 patients did not have ACA. Platelet counts of the high-risk ACA group (42.5×10(9)/L) were lower than those of the non-high-risk (141×10(9)/L) and non-ACA groups (109×10(9)/L) (χ(2)=4.968, P=0.083) . There was no significant difference in the incidence of point mutations in ABL kinase among the three groups (P=0.652) . The complete cytogenetic response of the high-risk ACA group (5.3% ) was significantly lower than that of the non-ACA group (46.7% ) (χ(2)=5.851, P=0.016) . The 5-year OS of the high-risk ACA group was lower than that of the non-ACA group (46.2% vs 77.8% , χ(2)=3.878, P=0.049) . Subgroup analysis revealed that the 5-year OS rate of the high-risk group Ⅱ, which included -7/7q-, i (17q) , and complex karyotype comprising ≥2 high-risk ACA, was significantly lower than that of the non-ACA group (28.6% vs 77.8% , χ(2)=8.035, P=0.005) whereas the 5-year OS rate was not significantly different between high-risk group Ⅰ, which included +8,+Ph, and complex ACA with +8/+Ph, and the non-ACA group (54.5% vs 77.8% , χ(2) =1.514, P=0.219) . Conclusion: Due to different disease stages and ACA/Ph(+) types, treatment response and prognosis vary among patients with CML harboring ACA/Ph(+). The emergence of high-risk ACA during therapy suggests worse therapy efficacy and prognosis. Strict and standardized cytogenetic monitoring is critical for early detection, precise diagnosis, and treatment of these patients.