ABSTRACT
Objective: To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children. Methods: A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People's Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors. Results: Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference (χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference (χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS (HR=1.97, 95%CI 1.11-3.49), PFS (HR=2.95, 95%CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions: ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Female , Child , Male , Retrospective Studies , Adolescent , Prognosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Kaplan-Meier Estimate , Survival Rate , Leukemia, Myeloid, Chronic-Phase/mortality , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukemia, Myeloid, Chronic-Phase/diagnosis , Proportional Hazards Models , Risk Factors , Survival Analysis , Disease-Free SurvivalABSTRACT
The outcome of chronic myeloid leukemia (CML) patients improved in the last decade. Clinical prognostic scoring systems aim to provide information about survival in the long-term, without determining from baseline the subset of patients who require a strictly monitoring because at increased risk of failure. Imatinib, the first-generation tyrosine kinase inhibitor (TKI), is still widely used as frontline treatment: recently, the imatinib therapy failure (IMTF) score was proposed to identify the failure free survival. Aim of our study was to validate this index in a large cohort of patients treated with imatinib.
Subject(s)
Antineoplastic Agents , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Humans , Imatinib Mesylate/adverse effects , Antineoplastic Agents/adverse effects , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/adverse effects , Treatment OutcomeSubject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Humans , Blast Crisis/drug therapy , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukemia, Myeloid, Chronic-Phase/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Protein Kinase Inhibitors/adverse effectsABSTRACT
Low-dose dasatinib is safe and effective in patients with chronic myeloid leukemia in chronic phase (CML-CP). No randomized trials have compared the outcome with standard-dose dasatinib. This study aims to compare the outcome of patients with CML-CP treated with frontline dasatinib 50 versus 100 mg/day. We analyzed 233 patients with newly diagnosed CML-CP treated with low-dose dasatinib (N = 83) or standard-dose dasatinib (N = 150). Propensity score analysis with 1:1 matching was performed and identified 77 patients in each cohort without significant baseline differences. Response rates were reported as the cumulative incidences of complete cytogenetic response, major molecular response (MMR), molecular response (MR)4, and MR4.5. Failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS) were also compared. Patients on low-dose dasatinib with suboptimal response by European LeukemiaNet (ELN) 2013 criteria had the option to increase the dose to 100 mg/day. The overall median follow-up time was 60 months. The 3-year MMR rates were 92% and 84% for low-dose and standard-dose dasatinib, respectively (p = .23). Dasatinib 50 mg/day induced higher cumulative incidence of MR4 (77% vs. 66%; p = .04) and MR4.5 (77% vs. 62%; p = .02) at 3 years. The 4-year FFS, EFS and OS rates were 89% versus 77% (p = .04), 95% versus 92% (p = .06), and 97% versus 96% (p = .78) with low-dose and standard-dose dasatinib, respectively. The rate of any grade pleural effusion was 5% with dasatinib 50 mg/day compared to 21% with 100 mg/day. Dasatinib 50 mg/day is at least as effective as 100 mg/day with a better safety profile and drug exposure.
Subject(s)
Antineoplastic Agents , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Antineoplastic Agents/adverse effects , Dasatinib/adverse effects , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Propensity Score , Protein Kinase Inhibitors/adverse effects , Treatment OutcomeABSTRACT
Cognitive function was assessed in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) therapy using the Montreal Cognitive Assessment (MoCA). Cross-sectional assessments of 100 newly diagnosed patients and 584 patients receiving TKI therapy for >1 year showed that 31 (31.0%) and 191 (32.7%) patients had mild cognitive impairment, respectively. In the multivariable analyses, higher percentages of blood blasts were associated with a worse MoCA score at diagnosis [ß = -0.29, 95% confidence interval (-0.54, -0.03), p = .027]; deeper molecular response [versus < major molecular response, ß = 0.74 (0.07, 1.40), p = .029], better MoCA score on TKI therapy. Increased MoCA scores were observed after 12 months of TKI therapy in 42 patients who were regularly followed up (p = .005). Lower tumor burden is associated with better cognitive function in CML-CP patients both at diagnosis and during TKI therapy.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Cognition , Cross-Sectional Studies , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Protein Kinase Inhibitors/adverse effects , Tumor BurdenABSTRACT
INTRODUCTION: Few studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: We retrospectively analysed the clinical features, treatment response, and long-term outcomes of 42 AYA patients, in comparison to older patients. The initial therapies of AYA patients between 2001 and 2016 included imatinib (n = 24), dasatinib (n = 13) and nilotinib (n = 5). RESULTS: In AYA patients, the peripheral blood (PB) white blood cell count and percentage of blasts at the diagnosis were significantly higher, haemoglobin levels were lower and the spleen size was larger. The major molecular response (MMR), event-free survival (EFS) and overall survival (OS) rates were comparable. A sub-analysis comparing imatinib to second-generation TKIs as the initial therapy also showed that their prognosis was comparable. DISCUSSION: In conclusion, the tumour burden at the diagnosis of CML-CP is higher in AYA patients; however, their prognosis was not worse in comparison to older patients treated with TKIs. KEY MESSAGESFew studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). This study showed the tumour burden at the diagnosis of CML-CP is higher in AYA pa tients; however, their prognosis was not worse in comparison to older patients treated with TKIs. Understanding the biological and non-biological features of AYA patients with CML-CP on TKI therapy is essential for better management and to improve the outcomes.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Adolescent , Humans , Imatinib Mesylate/adverse effects , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Young AdultABSTRACT
Chronic Myeloid Leukemia (CML) is one of the myeloproliferative disorders characterized by Philadelphia chromosome presence. Contrary to Western countries, most CML patients in Indonesia present symptoms with splenomegaly as the most common finding. It is rare to find asymptomatic CML patients. We present a case of asymptomatic chronic-phase chronic myeloid leukemia BCR-ABL (+) without splenomegaly who achieved a hematologic and molecular response to imatinib.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Splenomegaly/etiologyABSTRACT
The doubling time (DT) of the BCR-ABL1 quantitative polymerase chain reaction (qPCR) transcript level reflects the re-growing fraction of leukaemic cells after discontinuation of tyrosine kinase inhibitor (TKI). The present study analyzed monthly DT within six months after imatinib discontinuation in 131 patients. Monthly DT was calculated as x = ln(2)/K, where x is the DT and K is the fold BCR-ABL1 change from the previous value divided by the number of days between each measurement. The optimal DT value was determined as 12·75 days at two months using a recursive partitioning method. The patients were stratified into three groups: the high-risk group (DT<12·75 days but >0, with rapidly proliferating chronic myeloid leukaemia (CML) cells; n = 26) showed the lowest molecular relapse-free survival (mRFS) of 7·7% at 12 months, compared to 53·6% in the intermediate-risk group (DT≥12·75 days, with slowly proliferating CML cells; n = 16) or 90·0% in the low-risk group (DT≤0, i.e., without proliferating CML cells; n = 71; P < 0·001). Monthly assessment of DT helps identify high-risk patients for treatment-free remission failure with an imminent risk of molecular recurrence, and to define low-risk patients who can be spared the frequent monitoring of monthly molecular tests.
Subject(s)
Fusion Proteins, bcr-abl/genetics , Gene Expression Regulation, Leukemic , Imatinib Mesylate/therapeutic use , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukemia, Myeloid, Chronic-Phase/genetics , Adult , Aged , Biomarkers, Tumor , Child , Female , Humans , Imatinib Mesylate/administration & dosage , Imatinib Mesylate/adverse effects , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/mortality , Male , Middle Aged , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Real-Time Polymerase Chain Reaction , Recurrence , Remission Induction , Treatment Failure , Young AdultABSTRACT
Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of the pharmacokinetics (PK) of TKIs is currently unclear. We examined the PK of the third-generation TKI ponatinib to monitor side effects and efficacy during treatments for one patient with CML-chronic phase (CP-CML) and two who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), one for CML-blastic crisis (BC-CML) and one for Ph + ALL. The patient with CP-CML was intolerant to multiple TKIs (dasatinib, nilotinib, imatinib, and bosutinib) and thus was switched to ponatinib (15 mg/day). The patients who received allo-HSCT for BC-CML and Ph + ALL received ponatinib (15 mg/day) as maintenance therapy. Notably, serial evaluation of the PK of ponatinib showed that the median trough values (ng/ml) were 17.2 (12.2-34.5), 33.1 (21.2-40.3) and 27.7 (13.6-29.9) in patients 1, 2, and 3, respectively. These values were around the target concentration (23 ng/ml). All patients are maintaining complete remission without side effects. In conclusion, serial evaluation of PK of ponatinib may yield meaningful information about its safety and efficacy.
Subject(s)
Imidazoles/pharmacokinetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Protein Kinase Inhibitors/pharmacokinetics , Pyridazines/pharmacokinetics , Adult , Aged , Combined Modality Therapy , Drug Monitoring , Female , Fusion Proteins, bcr-abl/genetics , Hematopoietic Stem Cell Transplantation , Humans , Imidazoles/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Male , Middle Aged , Molecular Targeted Therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Protein Kinase Inhibitors/administration & dosage , Pyridazines/administration & dosage , Treatment OutcomeABSTRACT
ABSTRACT: The aim of this study was to evaluate the ability of the red blood cell distribution width (RDW) to predict prognosis and treatment response in chronic myeloid leukemia (CML)-chronic phase (CP) patients treated with tyrosine kinase inhibitor (TKIs).We retrospectively enrolled 93 newly diagnosed CML-CP patients treated with TKIs from 2009 to 2018 at the First Hospital of Lanzhou University. Patients were divided into 2 groups using an RDW of 18.65% determined by receiver operating characteristic curve analysis. We analyzed the correlation of treatment responses and the RDW compared to common scoring systems, as well as the correlation of the RDW with disease outcome, including overall survival (OS) and progression-free survival (PFS), and demographic and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used.The median age of patients was 40 years, and 51 patients (54.8%) were men. A high RDW could predict treatment response at 3 months (Pâ=â.03) and 6 months (Pâ=â.02). The RDW was significantly lower in patients who achieved molecular response by 3 months (Pâ<â.001) and complete cytogenetic response by 6 months (Pâ=â.001) than in those who did not respond. Patients with a high RDW (>18.65%, nâ=â35) had significantly worse 5-year OS (77.1% vs 96.6%; Pâ=â.008) and PFS (80.0% vs 98.3%; Pâ=â.002) than those with a low RDW (≤18.65%, nâ=â58). Multivariate analysis demonstrated that a high RDW was an adverse predictor of OS (Pâ=â.005, HR (hazard ratio)â=â9.741) and PFS (Pâ=â.009, HRâ=â16.735).The RDW is a readily available prognostic marker of outcome in patients with CML-CP and can predict treatment response to TKIs. Further larger and prospective studies are required.