Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.
Humans ; Male ; Adolescent ; Adult ; Female ; Protein Kinase Inhibitors/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Treatment Outcome ; Retrospective Studies ; Dasatinib/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Thrombocytopenia

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Antineoplastic Agents ; Dasatinib ; Humans ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Protein Kinase Inhibitors ; Pyrimidines/therapeutic use*

Antineoplastic Agents/therapeutic use* ; Dasatinib/therapeutic use* ; Humans ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Prognosis ; Protein Kinase Inhibitors ; Treatment Outcome

Objective: To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh). Methods: The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210. Results: There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients. 3(9.4%) of the 32 vPh cases were simple variant translocations. Among the remaining 29 cases with complex variant translocations, 28 cases (87.5%) involved 3 chromosomes, and only 1 (3.1%) involved 4 chromosomes. Except for 8, 15, 18, X, and Y chromosomes, the other chromosomes were involved. The frequency of chromosome 12q(15.5%) and 1p (12.1%) were higher involved. The most common FISH signal pattern was 2G2R1Y (74.1%), followed by 1G1R2F (14.8%), 2G1R1Y (3.7%), 1G2R1Y (3.7%), 1G1R1Y (3.7%). The comparison of complete cytogenetic response (CCyR) (P=0.269), major molecular response (MMR) (P=0.391) were carried out between simple and complex mechanisms, without difference. Compared with the classic Ph, the patients with vPh had higher IM primary resistance rate (χ²=3.978, P=0.046), especially primary hematological resistance (χ²=7.870, P=0.005), but the difference of CCyR (χ²=0.192, P=0.661), MMR (χ²=0.822, P=0.365), EFS (χ²=0.509, P=0.476), OS (χ²=3.485, P=0.062) were not statistically significant, and multivariate analysis showed that the presence of vPh did not affect OS (RR=0.692, 95%CI 0.393-1.765, P=0.658)、EFS (RR=0.893, 95%CI 0.347-2.132, P=0.126) and PFS (RR=1.176, 95%CI 0.643-2.682, P=0.703). Conclusion: CML-CP patients with vPh and classic Ph had similar demographic and hematological characteristics. Except for 22q11, 9q34, the frequency of chromosome 12q and 1p were higher involved. The most common FISH signal pattern was 2G2R1Y, and different mechanisms had no impact on TKIs therapy. Compared with cases with classic Ph chromosomes, the patients with vPh chromosomes had higher risk of IM primary resistance, especially primary hematological resistance, which can obtain deeper molecular response quickly after changing to second-generation TKIs and didn't affect long-term outcomes and OS.
Cytogenetics ; Fusion Proteins, bcr-abl ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Philadelphia Chromosome ; Protein Kinase Inhibitors/therapeutic use* ; Protein-Tyrosine Kinases

Capsules ; China ; Drugs, Generic ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase

Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Protein-Tyrosine Kinases ; antagonists & inhibitors

OBJECTIVETo explore efficacy of imatinib for patients with chronic myeloid leukemia(CML) and its resistance-related factors during the treatment.

METHODSThe clinical data of 214 CML patients received imatinib were analyzed respectively in our hospital from April 2005 to December 2010. The therapy history and efficacy of regular follow-up and factors influencing drug resistance were analyzed. COX regression analysis was used to perform the univariate and multivariate analysis.

RESULTSUntil the end of follow up, thirty-one patients (14.5%) occurred drug resistance. One of them was in accelerated phase(AP), and two in blast phase(BP); 69.2% of patients achieved a complete cytogenetic response(CCyR), and 31.3% of patients achieved a major molecular response(MMR). COX analysis was performed in 207 chronic phase(CP) patients. Univariate analysis showed that the course of disease before treatment, the hemoglobin count, the white blood cell count, whether achieved CCyR or not and whether achieved MMR or not were the influencing factors for imatinib resistance. Multivariate analysis showed that whether achieved CCyR or not was the independent factor for drug resistance.

CONCLUSIONWhether achieved CCyR or not is an independent factor and also a protective factor for imatinib resistance in patients with CML.

Adolescent ; Adult ; Aged ; Benzamides ; therapeutic use ; Child ; Child, Preschool ; Drug Resistance, Neoplasm ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Young Adult

OBJECTIVEMeta-analysis of the efficiencies of imatinib mesylate (IM) with or without interferon for chronic myeloid leukemia-chronic phase (CML-CP) patients.

METHODSPublished studies of IM with or without interferon for CML-CP patients as first-line therapy were collected from PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) of the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP information and WANFANG database. References of retrieved articles were also identified. The quality of each randomized controlled trial (RCT) was evaluated by the Cochrane collaboration's tool for assessing the risk of bias. Data analysis was performed with RevMan 5.1.

RESULTSA total of 5 articles involving 1754 patients were included. Meta-analysis results showed that there were no statistical differences between IM with interferon and IM monotherapy for the complete cytogenetic response (CCyR) rate at 12 months,but IM with interferon could improve major molecular response (MMR) rate at 12 months (OR=1.57, 95% CI: 1.26-1.96, P=0.02). Furthermore, IM combined with pegylated-interferon demonstrated superiority for MMR at 12 months (OR=2.43, 95% CI: 1.78-3.33, P<0.01).

CONCLUSIONCombination of IM and interferon does not increase CCyR rate, but improve MMR rate at 12 months.

Benzamides ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Humans ; Imatinib Mesylate ; Interferons ; administration & dosage ; therapeutic use ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Piperazines ; administration & dosage ; therapeutic use ; Pyrimidines ; administration & dosage ; therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

OBJECTIVETo compare the efficacy and safety of dasatinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP).

METHODS37 CML-CP patients were randomized to receive dasatinib 100 mg orally daily or imatinib 400 mg orally daily. The efficacy and safety data were collected and compared.

RESULTSOf 37 CML-CP patients, 18 received dasatinib and 19 received imatinib. The both of median duration of drug therapy and follow-up were 38 months. (1) The rate of complete cytogenetic response (CCyR) at 12 months was higher in dasatinib group than in imatinib group (89% vs 68%), but there was no significantly statistic significance between two groups (P = 0.232). The cumulative CCyR rate by 36 months was 89% in both arms. The major molecular response (MMR) at 18 months was 76% in dasatinib arm, being significantly higher than that in imatinib arm (37%) (P = 0.017). The cumulative MMR rate by 36 months was 82% versus 68% in dasatinib or imatinib (P = 0.694). The median time to CCyR and MMR was significantly faster for dasatinib than for imatinib (3 months vs. 6 months, and 14 months vs. 34 months, respectively). (2) The drug-related adverse events were mostly grade 1/2 and were well-tolerated. Increase of serum glutamic pyruvic transaminase, pleural effusion and thrombocytopenia were more common in dasatinib arm, while hypophosphatemia, edema and neutropenia were more common in imatinib arm.

CONCLUSIONDasatinib is an effective and safe therapy option and can be used as first-line therapy for newly diagnosed CML-CP patients.

Adult ; Aged ; Benzamides ; adverse effects ; therapeutic use ; Dasatinib ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Male ; Middle Aged ; Piperazines ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Survival Rate ; Thiazoles ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult