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Patients with chronic myeloid leukemia (CML) now have an improved life expectancy similar to that of the general population due to the introduction of tyrosine kinase inhibitors (TKIs). However, many patients experience mild to severe adverse events while undergoing TKI treatment. This review aimed to discuss the adverse events of TKIs, including myocardial infarction and hypertension, and comprehensively analyze strategies for minimizing vascular complications.Current Concepts: Near-fatal cardiovascular events (CVEs) are common among patients receiving nilotinib and ponatinib. However, those receiving other TKIs, such as imatinib and dasatinib, rarely experience CVEs. Among these CVEs, vascular complications, including peripheral arterial occlusion, venous occlusion, and hypertension, are exacerbated in patients with pre-existing vascular risk factors and prolonged TKI use. Therefore, it is crucial to assess predisposing factors to vascular complications and select the optimal TKI to minimize serious CVEs before initiating therapy. Additionally, patients should be closely monitored for vascular complications during nilotinib and ponatinib treatment.Discussion and Conclusion: Despite advancements in therapeutic approaches and research on CML leading to the development of target-specific TKIs aiming to minimize side effects, newer generations are not entirely devoid of adverse events. Hence, it is important for patients and physicians to be knowledgeable about these medications to effectively monitor for side effects, particularly those that are life-threatening, such as vascular toxicity. It is now more important than ever to carefully observe symptoms and perform adequate testing to identify at-risk individuals early and avoid preventable adverse events.
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Background/Aims@#Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. @*Methods@#Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). @*Results@#Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). @*Conclusions@#Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
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Chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cell accumulation and highly variable clinical manifestations that range from an indolent to an aggressive course, is rare in Korea. Asymptomatic patients with early stage CLL can be followed up without treatment; however, those with active or advanced disease require treatment immediately after diagnosis, for symptom alleviation and prolonging survival. Previously, chemotherapy using cytotoxic agents was the only therapeutic option available for patients with CLL. Research has provided a deeper understanding of the pathophysiology of the disease, and novel agents such as monoclonal antibodies and small-molecule inhibitors that target specific sites on leukemic cells have been introduced. The advent of these new drugs has led to improved clinical outcomes in patients with CLL. Currently, Bruton’s tyrosine kinase inhibitors or B-cell lymphoma-2 inhibitors are recommended as frontline therapy, prior to the administration of cytotoxic agents or combination therapy with monoclonal antibodies. In this article, we review the diagnosis and prognosis of CLL, in addition to the clinical implications of the various therapeutic options.
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Background@#We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. @*Methods@#We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. @*Results@#Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). @*Conclusion@#We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.
ABSTRACT
Chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cell accumulation and highly variable clinical manifestations that range from an indolent to an aggressive course, is rare in Korea. Asymptomatic patients with early stage CLL can be followed up without treatment; however, those with active or advanced disease require treatment immediately after diagnosis, for symptom alleviation and prolonging survival. Previously, chemotherapy using cytotoxic agents was the only therapeutic option available for patients with CLL. Research has provided a deeper understanding of the pathophysiology of the disease, and novel agents such as monoclonal antibodies and small-molecule inhibitors that target specific sites on leukemic cells have been introduced. The advent of these new drugs has led to improved clinical outcomes in patients with CLL. Currently, Bruton’s tyrosine kinase inhibitors or B-cell lymphoma-2 inhibitors are recommended as frontline therapy, prior to the administration of cytotoxic agents or combination therapy with monoclonal antibodies. In this article, we review the diagnosis and prognosis of CLL, in addition to the clinical implications of the various therapeutic options.
ABSTRACT
Background@#We analyzed cell-free serum Epstein‒Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. @*Methods@#We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. @*Results@#Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P =0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P =0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P =0.008) and the International Prognostic Index (P =0.009). EBV positivity was also associated with higher disease relapse (P =0.038) and death rates (P =0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P =0.053) and overall survival (OS) (P =0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P =0.003) and OS (P =0.033). @*Conclusion@#We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.
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Background@#This study attempted to identify novel prognostic factors in patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using magnetic resonance imaging (MRI). @*Methods@#We retrospectively evaluated 67 patients diagnosed with central nervous system (CNS) tumors. The enrollment criteria were as follows: i) pathologic diagnosis of CNS lymphoma, ii) no evidence of systemic involvement, iii) no evidence of human immunodeficiency virus-1 infection or other immunodeficiencies, and iv) MRI scans available at diagnosis. Fifty-two patients met these criteria and were enrolled. @*Results@#The 3-year overall survival (OS) and failure-free survival rates were 69.7% and 45.6%, respectively, with a median follow-up duration of 36.2 months. OS of patients with low apparent diffusion coefficient (ADC) was lower than those with higher ADC. Multivariate analysis revealed that old age (＞60 yr) [hazard ratio (HR), 20.372; P=0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR, 10.429; P ＜ 0.001), higher lactate dehydrogenase (LDH) levels (HR, 7.408; P =0.001), and low ADC (HR, 0.273; P=0.009) were associated with lower OS. We modified the conventional prognostic scoring system using low ADC, old age (＞60 yr), ECOG PS ≥2, and higher LDH. The risk of death was categorized as high (score 3-4), intermediate-2 (score 2), intermediate- 1 (score 1), and low (score 0), with three-year OS rates of 33.5%, 55.4%, 88.9%, and 100%, respectively. @*Conclusion@#ADC demonstrated significant prognostic value for long-term survival in patients with newly diagnosed PCNSL. Low ADC was an independent unfavorable prognostic factor, suggesting that ADC obtained from MRI can improve the current prognostic scoring system.
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BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1(wt)/FLT3-ITD(neg/low)) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1(wt)/FLT3-ITD(neg/low), complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1(wt)/FLT3-ITD(neg/low) group (P=0.233). Among the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients. Well controlled studies are needed to confirm the current results.
Subject(s)
Humans , Cell Transplantation , Classification , Consolidation Chemotherapy , Induction Chemotherapy , Leukemia, Myeloid, Acute , Multivariate Analysis , Patient Selection , Protein-Tyrosine Kinases , Retrospective Studies , TransplantsABSTRACT
BACKGROUND: Elderly patients with multiple myeloma (MM) are vulnerable to adverse events (AEs). This study evaluated adherence to chemotherapy and treatment outcomes in elderly patients treated with a frontline bortezomib (BTZ), melphalan, and prednisone (VMP) regimen and regimens without BTZ.METHODS: One-hundred and forty elderly patients who were diagnosed with MM from March 2007 to March 2015 were included in this retrospective study. To evaluate regimen adherence, patients who were treated with more than 4 cycles were assigned to the good adherence group.RESULTS: Among the 140 patients, 71 were treated with a frontline VMP and 69 with non-BTZ regimens. The median age was 71 years (range, 65-90 years). The VMP group showed a higher complete response rate than the non-BTZ group: 26.8% vs. 7.2%. More patients in the VMP group achieved ≥ very good partial response (VGPR) and ≥ PR. In the VMP group, 27 patients (38.0%) received less than 4 cycles. The VMP good adherence group showed a higher 3-year overall survival (OS) rate (70.9%) than the poor adherence group (60.2%, p=0.059). In the multivariate analysis, treatment with ≥ 4 cycles of VMP was a favorable factor for OS.CONCLUSION: A good adherence to a frontline VMP regimen resulted in favorable long-term survival. Adequate management of AEs will be needed to achieve favorable outcomes in elderly patients with MM.
Subject(s)
Aged , Humans , Bortezomib , Drug Therapy , Medication Adherence , Melphalan , Multiple Myeloma , Multivariate Analysis , Prednisone , Retrospective StudiesABSTRACT
BACKGROUND@#Elderly patients with multiple myeloma (MM) are vulnerable to adverse events (AEs). This study evaluated adherence to chemotherapy and treatment outcomes in elderly patients treated with a frontline bortezomib (BTZ), melphalan, and prednisone (VMP) regimen and regimens without BTZ.@*METHODS@#One-hundred and forty elderly patients who were diagnosed with MM from March 2007 to March 2015 were included in this retrospective study. To evaluate regimen adherence, patients who were treated with more than 4 cycles were assigned to the good adherence group.@*RESULTS@#Among the 140 patients, 71 were treated with a frontline VMP and 69 with non-BTZ regimens. The median age was 71 years (range, 65-90 years). The VMP group showed a higher complete response rate than the non-BTZ group: 26.8% vs. 7.2%. More patients in the VMP group achieved ≥ very good partial response (VGPR) and ≥ PR. In the VMP group, 27 patients (38.0%) received less than 4 cycles. The VMP good adherence group showed a higher 3-year overall survival (OS) rate (70.9%) than the poor adherence group (60.2%, p=0.059). In the multivariate analysis, treatment with ≥ 4 cycles of VMP was a favorable factor for OS.@*CONCLUSION@#A good adherence to a frontline VMP regimen resulted in favorable long-term survival. Adequate management of AEs will be needed to achieve favorable outcomes in elderly patients with MM.