Cancer Research and Treatment

Original Articles

Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric and Young Adult Patients with Chronic Myeloid Leukemia in Tyrosine Kinase Inhibitor Era: A Study of the Korean Blood and Marrow Transplantation Registry: Hee Young Ju, Hyoung Soo Choi, Hyeon Jin Park, Keon Hee Yoo, Chuhl Joo Lyu, Ho Joon Im, Min Kyoung Kim, Yeung-Chul Mun, Joon Ho Moon, Sung-Soo Yoon, Eunyoung Lee, Jae Hoon Lee, Je-Hwan Lee, So Young Chong, June-Won Cheong, Seunghyun Won, on behalf of the Korean Society of Blood and Marrow Transplantation; Received December 10, 2024 Accepted April 29, 2025 Published online May 7, 2025; DOI: https://doi.org/10.4143/crt.2024.1186 [Accepted]

Abstract PDF: Purpose
Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era.
Materials and Methods
A retrospective analysis of 35 CML patients aged <40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age <20 years at HSCT (Group 1, n=15) and 20-40 years at HSCT (Group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan–Meier method.
Results
The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in Group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in Group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003) and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11).
Conclusion
When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.

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Literature-Guided 6-Gene Signature for the Stratification of High-Risk Acute Myeloid Leukemia: Jong Keon Song, Dong Hyeok Lee, Hyery Kim, Sang-Hyun Hwang; Received November 20, 2024 Accepted January 22, 2025 Published online January 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1114 [Accepted]

Abstract PDF: Purpose
Acute myeloid leukemia (AML) shows significant heterogeneity in therapeutic responses. We aimed to develop a gene signature for the stratification of high-risk pediatric AML using publicly available AML datasets, with a focus on literature-based prognostic gene sets. Materials and Methods We identified 300 genes from 12 well-validated studies on AML-related gene signatures. Clinical and gene expression data were obtained from three datasets: TCGA-LAML, TARGET-AML, and BeatAML. Least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was used to perform the initial gene selection and to construct a prognostic model using the TCGA database (n=132). The final gene signature was validated with two independent cohorts: BeatAML (n=411) and TARGET-AML (n=187).
Results
We identified a six-gene signature (ETFB, ARL6IP5, PTP4A3, CSK, HS3ST3B1, PLA2G4A), referred to as the literature-based signature 6 (LBS6), that was significantly associated with lower overall survival rates across the TCGA (HR=4.2, 95% CI: 2.59–6.81, p<0.0001), BeatAML (HR=1.52, 95% CI: 1.17–1.96, p=0.0013), and TARGET (HR=2.05, 95% CI: 1.36–3.08, p<0.001) datasets. The high-LBS6 score group exhibited significantly poorer five-year event-free survival compared to the low-LBS6 score group (HR=2.09, 95% CI: 1.38–3.15, p<0.001). After adjusting for key risk factors, including gene mutations (WT1, FLT3, and NPM1), protocol-based risk group, WBC count, and age, the LBS6 score was independently associated with worse survival rates in validation cohorts.
Conclusion
Our literature-driven approach identified a robust gene signature that stratifies AML patients into distinct risk groups. The LBS6 score shows promise in redefining initial risk stratification and identifying high-risk AML patients.

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Pediatric cancer

Survival of Children with Acute Lymphoblastic Leukemia with Risk Group–Based Protocol Changes: A Single-Center Experience with 460 Patients over a 20-Year Period: Na Hee Lee, Hee Young Ju, Eun Sang Yi, Young Bae Choi, Keon Hee Yoo, Hong Hoe Koo; Cancer Res Treat. 2025;57(2):558-569. Published online September 27, 2024; DOI: https://doi.org/10.4143/crt.2024.127

Abstract PDF Supplementary Material PubReader ePub: Purpose
Recent treatments for pediatric acute lymphoblastic leukemia (ALL) are founded on risk stratification. We examined the survival rates and prognostic factors of patients over a 20-year period at a single institution.
Materials and Methods
This study analyzed patients diagnosed with ALL and treated at the Pediatric Department of Samsung Medical Center (SMC). Patients were categorized into standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. The SMC protocol for the HR group underwent two changes during the study period: a modified Children’s Cancer Group (CCG)-1882 protocol was used from 2000 to 2005, the Korean multicenter HR ALL-0601 protocol from 2006 to 2014, and the Korean multicenter HR ALL-1501 protocol from 2015 to 2019.
Results
Of the 460 patients, complete remission was achieved in 436 patients (94.8%). The 10-year overall survival rate (OS) was 83.8±1.9% for all patients. OS according to the SMC risk group was as follows: 95.9%±1.4% in the SR group, 83.8%±3.6% in the HR group, and 66.2%±6.9% in the VHR group. The 5-year OS within the HR group varied according to the treatment protocol: 73.9%±7.5%, in the modified CCG-1882 protocol, 83.0%±3.9%, in the 0601 protocol, and 96.2%±2.6%, in the 1501 protocol. For those aged 15 years and older, the OS was only 56.5%±13.1%. Relapse occurred in 71 patients (15.4%), and the OS after relapse was 37.7%±6.0%.
Conclusion
The treatment outcomes of patients with ALL improved markedly. However, there is a need to further characterize adolescents and young adult patients, as well as those who have experienced relapses.

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The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia: Hee Young Ju, Na Hee Lee, Eun Sang Yi, Young Bae Choi, So Jin Kim, Ju Kyung Hyun, Hee Won Cho, Jae Kyung Lee, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo; Cancer Res Treat. 2025;57(1):240-249. Published online July 5, 2024; DOI: https://doi.org/10.4143/crt.2024.155

Abstract PDF PubReader ePub: Purpose
Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups.
Materials and Methods
A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease.
Results
Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment.
Conclusion
HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

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Hematologic malignancy

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia: Jun-Xia Wang, Miao-Miao Yang, Li-Peng Liu, Hui-Min Zhang, Meng-Chuan Wang, Yu-Wen Chen, Xiao-Ying Zang, Fang Hu; Cancer Res Treat. 2023;55(3):1023-1030. Published online February 6, 2023; DOI: https://doi.org/10.4143/crt.2022.1618

Abstract PDF PubReader ePub: Purpose
This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices.
Materials and Methods
Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated.
Results
Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia.
Conclusion
TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

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Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia: Seo-Yeon Ahn, TaeHyung Kim, Mihee Kim, Ga-Young Song, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim; Cancer Res Treat. 2023;55(3):1011-1022. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1407

Abstract PDF PubReader ePub

Purpose
We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIP^in-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods
Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results
Among 78 of a total of 395 patients (19.7%), 50 had bZIP^in-f CEBPA, and 28 had non-bZIP^in-f CEBPA. In the multivariate analysis, patients with NPM1^mut, those with bZIP^in-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITD^mut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP^in-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITD^pos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPA^dm), bZIP^in-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP^in-f CEBPA. Of 50 patients with bZIP^in-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIP^in-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
Only bZIP^in-f CEBPA was associated with favorable outcomes in patients with CEBPA^dm. However, some mutations accompanying bZIP^in-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP^in-f CEBPA.

Citations

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CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
Seung Jun Choi, Hyun Kyung Kim, Eun Jung Suh, Soon Sung Kwon, Saeam Shin, Seung-Tae Lee, Sinyoung Kim
Blood Advances.2024; 8(6): 1487. CrossRef
CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications
Fenghong Zhang, Zhen Shen, Jundan Xie, Jingren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen
Blood Cancer Journal.2024;[Epub] CrossRef
Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia
Juan Carlos Rivera, Daniel Nuñez, Elizabet Millar, Kimberly Ramirez, Mauricio Chandía, Claudio Aguayo
International Journal of Laboratory Hematology.2023; 45(6): 833. CrossRef

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Lung and Thoracic cancer

MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis: Yang Yang, Rongfang Qiu, Qiaoyou Weng, Ziwei Xu, Jingjing Song, Siyu Zhao, Miaomiao Meng, Dengke Zhang, Chunli Kong, Hailin Wang, Min Xu, Zhongwei Zhao, Jiansong Ji; Cancer Res Treat. 2023;55(3):778-803. Published online January 26, 2023; DOI: https://doi.org/10.4143/crt.2022.1042

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis.
Materials and Methods
RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
Results
We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
Conclusion
Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

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KMT2D Induces M1 Macrophage Polarization to Repress Non-small Cell Lung Cancer Progression via Transcription Activation of ITGAL
Wen-Tao Wang, Jie Yang, Peng-Fei Jiang
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Jingtao Wang, Fan Yang, Yurou Chen, Yuzhu Xing, Juyuan Huang, Jing Cao, Jiaqiang Xiong, Yanyan Liu, Qiuyan Zhao, Manwen Luo, Jie Xiong, Guanlan Fan, Qiongying Lyu, Feng Li, Wei Zhang
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Linxiang Zhang, Xueying Zhang, Yan Shi, Yuhan Ni, Jiaojiao Fei, Zhixin Jin, Wenjuan Li, Xiaojing Wang, Nan Wu
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The multifaceted role of SOX2 in breast and lung cancer dynamics
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Pathology - Research and Practice.2024; 260: 155386. CrossRef
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Yingjie Jia, Pengxing He, Xubin Ma, Kaili Lv, Ying Liu, Yichao Xu
European Journal of Pharmacology.2024; 977: 176753. CrossRef
UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway
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Pediatric cancer

Outcome of Intensive Therapy for Children with Relapsed Acute Myeloid Leukemia: A Single Institution Korean Study: Jae Wook Lee, Jae Won Yoo, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho; Cancer Res Treat. 2022;54(4):1230-1239. Published online December 17, 2021; DOI: https://doi.org/10.4143/crt.2021.1011

Abstract PDF Supplementary Material PubReader ePub

Purpose
Approximately 30%-40% of pediatric acute myeloid leukemia (AML) patients relapse. In this study, we analyzed the outcome and prognostic factors of relapsed AML patients who had previously received first-line therapy at our institution.
Materials and Methods
The study group consisted of 50 patients who had been diagnosed with AML from April 2009 to December 2018, and then showed first relapse. Thirty-two of the patients (64%) had previously received allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR).
Results
Forty-five of the patients (90%) received intensive chemotherapy upon diagnosis of relapse, and 76% (34/45) of these patients achieved a second CR. Estimated 5-year overall survival for these 45 patients was 44.9%±7.6%. Time from diagnosis to relapse, extramedullary involvement (EMI) at diagnosis, core binding factor AML, and complex karyotype were significant prognostic factors; in multivariate study, both time from diagnosis to relapse and EMI at diagnosis proved significant. There was no difference in 5-year disease-free survival between patients previously treated with chemotherapy only and those who received HSCT in first CR (52.4%±14.9% vs. 52.6%±11.5%). Of the 19 patients who achieved second CR after previous allogeneic HSCT in first CR and subsequent relapse, 11 were treated with chemotherapy only, and seven survive disease-free.
Conclusion
Intensive therapy allowed for long-term survival in 40%-50% of patients, and 50% of patients who achieved second CR, regardless of prior treatment modalities in first CR. Intensive treatment may allow for salvage of a significant portion of patients with relapsed pediatric AML.

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TREML2 enhances sensitivity of acute myeloid leukemia cells to chemotherapy by inhibiting the NF-κB/CXCL10 pathway
Xin Zhang, Shuheng Yan, Xuehong Zhang, Dan Huang, Jiayin Zhou, Xiaoting Song, Yuchao Hao, Xijia Wang, Jinsong Yan
Blood Science.2025; 7(2): e00223. CrossRef
Diagnosis and Treatment of Pediatric Acute Megakaryoblastic Leukemia with NUP98::KDM5A Rearrangement: Case Report
Hyemin Kang, Suejung Jo, Jae Won Yoo, Seongkoo Kim, Jae Wook Lee, Nack-Gyun Chung, Bin Cho, Chae Yeon Lee, Myungshin Kim
Clinical Pediatric Hematology-Oncology.2024; 31(2): 56. CrossRef

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Epidemiology of Acute Leukemia among Children with Down Syndrome in Korea: Young Bae Choi, Keon Hee Yoo; Cancer Res Treat. 2022;54(2):572-578. Published online August 10, 2021; DOI: https://doi.org/10.4143/crt.2021.368

Abstract PDF PubReader ePub

Purpose
Children with Down syndrome (DS) show a higher risk of acute leukemia than those without DS. In this study, we investigated the nationwide incidence of acute leukemia among children with DS and compared their epidemiologic characteristics with those of children with acute leukemia but without DS.
Materials and Methods
Using the National Health Insurance Service database, we selected patients with acute leukemia aged 0–19 years at diagnosis between 2007 and 2016.
Results
Among the 4,697 children with acute leukemia, 54 (1.1%) had DS. The median incidence rate of leukemia with DS by year was 1.3% (range, 0.2%–2.0%). Sixteen patients with acute lymphoblastic leukemia (ALL; 29.6%) and 36 with acute myeloid leukemia (AML; 66.7%) had DS. The DS group showed younger age at diagnosis than the non-DS group, and diagnosis of AML was more frequent in the DS group than in the non-DS group (3 years vs. 9 years, p<0.001; 66.7% vs. 32.4%, P<0.001, respectively). The 5-year overall survival was comparable between the DS and non-DS groups (88.0% vs. 81.9%, p=0.375). Among all the Koreans born between 2007 and 2008, the incidences of acute leukemia, ALL, and AML were 49.25, 20.75, and 163.38 times higher, respectively, in the DS group than in the non-DS group.
Conclusion
Our findings support the fact that the incidence of acute leukemia is higher among patients with DS than among those without DS in Korea. However, the DS and non-DS groups in this study had a comparable overall survival rate.

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Cancer risks related to intellectual disabilities: A systematic review
Amina Banda, Jenneken Naaldenberg, Aura Timen, Agnies van Eeghen, Geraline Leusink, Maarten Cuypers
Cancer Medicine.2024;[Epub] CrossRef

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Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group: Kyung Mi Park, Keon Hee Yoo, Seong Koo Kim, Jae Wook Lee, Nack-Gyun Chung, Hee Young Ju, Hong Hoe Koo, Chuhl Joo Lyu, Seung Min Han, Jung Woo Han, Jung Yoon Choi, Kyung Taek Hong, Hyoung Jin Kang, Hee Young Shin, Ho Joon Im, Kyung-Nam Koh, Hyery Kim, Hoon Kook, Hee Jo Baek, Bo Ram Kim, Eu Jeen Yang, Jae Young Lim, Eun Sil Park, Eun Jin Choi, Sang Kyu Park, Jae Min Lee, Ye Jee Shim, Ji Yoon Kim, Ji Kyoung Park, Seom Gim Kong, Young Bae Choi, Bin Cho, Young Tak Lim; Cancer Res Treat. 2022;54(1):269-276. Published online April 20, 2021; DOI: https://doi.org/10.4143/crt.2021.313

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Purpose
Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.
Materials and Methods
Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.
Results
Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×10⁹/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×10⁹/L than in those with initial WBC ≥ 10×10⁹/L (p=0.020).
Conclusion
This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

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Lila Krebs-Drouot, Georgia Karpathiou, Virginie Scolan, Carolyne Bidat-Callet, Baptiste Boyer, Michel Péoc’h
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Successful Treatment of Isolated Central Nervous System Relapse with Intrathecal Chemotherapy in an Adolescent with Acute Promyelocytic Leukemia
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Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea: Jung Yoon Choi, Che Ry Hong, Kyung Taek Hong, Hyoung Jin Kang, Seongkoo Kim, Jae Wook Lee, Pil Sang Jang, Nack-Gyun Chung, Bin Cho, Hyery Kim, Kyung-Nam Koh, Ho Joon Im, Jong Jin Seo, Seung Min Hahn, Jung Woo Han, Chuhl Joo Lyu, Eu Jeen Yang, Young Tak Lim, Keon Hee Yoo, Hong Hoe Koo, Hoon Kook, In Sang Jeon, Hana Cho, Hee Young Shin; Cancer Res Treat. 2021;53(4):1184-1194. Published online January 4, 2021; DOI: https://doi.org/10.4143/crt.2020.289

Abstract PDF Supplementary Material PubReader ePub

Purpose
Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development.
Materials and Methods
In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed.
Results
Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events.
Conclusion
Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

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Zan Liu, Zitong Zhao, Longlong Xie, Zhenghui Xiao, Ming Li, Yong Li, Ting Luo
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3′-O-β-Glucosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase
Jonathan P. Dolan, Tessa Keenan, Aisling Ní Cheallaigh, Martin A. Fascione, Gavin J. Miller
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Hematologic malignancy

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia: Jae Wook Lee, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho; Cancer Res Treat. 2021;53(2):567-575. Published online October 8, 2020; DOI: https://doi.org/10.4143/crt.2020.507

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recent cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) of greater than 80%. In this study, we analyzed the outcome and prognostic factors for patients with precursor B cell ALL (n=405) diagnosed during a 10-year period (2005-2015) at our institution.
Materials and Methods
All patients were treated with a uniform institutional regimen based on four risk groups, except for steroid type; patients diagnosed up till 2008 receiving dexamethasone, while subsequent patients received prednisolone. None of the patients received cranial irradiation in first complete remission.
Results
The 10-year EFS and overall survival was 76.3%±2.3% and 85.1%±1.9%. Ten-year cumulative incidence of relapse, any central nervous system (CNS) relapse and isolated CNS relapse was 20.8%±2.2%, 3.7%±1.1% and 2.5%±0.9% respectively. A comparison of established, good prognosis genetic abnormalities showed that patients with high hyperdiploidy had significantly better EFS than those with ETV6-RUNX1 rearrangement (10-year EFS of 91.2%±3.0% vs. 79.5%±4.4%, p=0.033). For the overall cohort, male sex, infant ALL, initial CNS involvement, and Philadelphia chromosome (+) ALL were significant factors for lower EFS in multivariate study, while high hyperdiploidy conferred favorable outcome. For high and very high risk patients (n=231), high hyperdiploidy was the only significant factor for EFS in multivariate study.
Conclusion
Regarding good prognosis genetic abnormalities, patients with high hyperdiploidy had significantly better outcome than ETV6-RUNX1 (+) patients. High hyperdiploidy was a major, favorable prognostic factor in the overall patient group, as well as the subgroup of patients with higher risk.

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Diagnostic and therapeutic advances in adults with acute lymphoblastic leukemia in the era of gene analysis and targeted immunotherapy
Jae-Ho Yoon, Seok Lee
The Korean Journal of Internal Medicine.2024; 39(1): 34. CrossRef
The potential role of RNA sequencing in diagnosing unexplained insensitivity to conventional chemotherapy in pediatric patients with B-cell acute lymphoblastic leukemia
Xinyu Li, Zaoli Huang, Liwen Zhu, Weixin Lai, Yunyao Li, Han Chen, Diandian Liu, Junjiu Huang, Dunhua Zhou, Yang Li, Wenjun Weng, Honggui Xu, Luhong Xu, Zhenhua Luo, Jianpei Fang
BMC Medical Genomics.2024;[Epub] CrossRef
Distinct Immunophenotypes in the DNA Index-Based Stratification of Pediatric B-Cell Acute Lymphoblastic Leukemia
Myriam Campos-Aguilar, Wilfrido David Tapia-Sánchez, Alberto Daniel Saucedo-Campos, Carlos Leonardo Duarte-Martínez, Sandra Olivas-Quintero, Almarosa Ruiz-Ochoa, Adolfo Rene Méndez-Cruz, Julia Reyes-Reali, María Isabel Mendoza-Ramos, Rafael Jimenez-Flores
Cancers.2024; 16(21): 3585. CrossRef
The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21)
Agnieszka Kaczmarska, Justyna Derebas, Michalina Pinkosz, Maciej Niedźwiecki, Monika Lejman
Cells.2023; 12(3): 357. CrossRef
Overview on Aneuploidy in Childhood B-Cell Acute Lymphoblastic Leukemia
Kinga Panuciak, Emilia Nowicka, Angelika Mastalerczyk, Joanna Zawitkowska, Maciej Niedźwiecki, Monika Lejman
International Journal of Molecular Sciences.2023; 24(10): 8764. CrossRef
Construction of three‐gene‐based prognostic signature and analysis of immune cells infiltration in children and young adults with B‐acute lymphoblastic leukemia
Chunli Xiang, Jie Wu, Liang Yu
Molecular Genetics & Genomic Medicine.2022;[Epub] CrossRef
Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group
Kun-yin Qiu, Hong-gui Xu, Xue-qun Luo, Hui-rong Mai, Ning Liao, Li-hua Yang, Min-cui Zheng, Wu-qing Wan, Xue-dong Wu, Ri-yang Liu, Qi-wen Chen, Hui-qin Chen, Xiao-fei Sun, Hua Jiang, Xing-jiang Long, Guo-hua Chen, Xin-yu Li, Chang-gang Li, Li-bin Huang, Y
Frontiers in Oncology.2021;[Epub] CrossRef

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EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia: Dan-Min Xu, Yi-Lin Kong, Li Wang, Hua-Yuan Zhu, Jia-Zhu Wu, Yi Xia, Yue Li, Shu-Chao Qin, Lei Fan, Jian-Yong Li, Jin-Hua Liang, Wei Xu; Cancer Res Treat. 2020;52(2):492-504. Published online October 29, 2019; DOI: https://doi.org/10.4143/crt.2019.457

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene.
Materials and Methods
Quantitative reverse transcription–polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL.
Results
p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3′- untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1- 1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines.
Conclusion
This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

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Seyedeh Zahra Bahojb Mahdavi, Asiyeh Jebelli, Parisa Shiri Aghbash, Behzad Baradaran, Mohammad Amini, Fatemeh Oroojalian, Nasser Pouladi, Hossein Bannazadeh Baghi, Miguel de la Guardia, Amir Ali Mokhtarzadeh
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USP7 Inhibitors Destabilize EBNA1 and Suppress Epstein‐Barr Virus Tumorigenesis
Christopher Chen, Kush Addepalli, Samantha S. Soldan, Leonardo Josue Castro‐ Munoz, Sarah Preston‐Alp, Rishi J. Patel, Coltin J. Albitz, Hsin‐Yao Tang, Italo Tempera, Paul M. Lieberman
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The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy
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Epstein-Barr virus deubiquitinating enzyme BPLF1 is involved in EBV carcinogenesis by affecting cellular genomic stability
Hantao Wu, Bo-Wei Han, Tiancai Liu, Min Zhang, Yingsong Wu, Jing Nie
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Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology
Rodney Hull, Rahaba Marima, Mohammed Alaouna, Demetra Demetriou, Rui Manuel Reis, Thulo Molefi, Zodwa Dlamini
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MicroRNAs: Tiny Regulators of Gene Expression with Pivotal Roles in Normal B-Cell Development and B-Cell Chronic Lymphocytic Leukemia
Katerina Katsaraki, Paraskevi Karousi, Pinelopi I. Artemaki, Andreas Scorilas, Vasiliki Pappa, Christos K. Kontos, Sotirios G. Papageorgiou
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Metabolic Control by DNA Tumor Virus-Encoded Proteins
Martin A. Prusinkiewicz, Joe S. Mymryk
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Alessia Gallo, Matteo Bulati, Vitale Miceli, Nicola Amodio, Pier Giulio Conaldi
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EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives
Keran Sun, Keqi Jia, Huifang Lv, Sai-Qi Wang, Yan Wu, Huijun Lei, Xiaobing Chen
Frontiers in Oncology.2020;[Epub] CrossRef

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Diabetes Mellitus Is Associated with Inferior Prognosis in Patients with Chronic Lymphocytic Leukemia: A Propensity Score-Matched Analysis: Rui Gao, Tian-Shuo Man, Jin-Hua Liang, Li Wang, Hua-Yuan Zhu, Wei Wu, Lei Fan, Jian-Yong Li, Tao Yang, Wei Xu; Cancer Res Treat. 2020;52(1):189-206. Published online July 1, 2019; DOI: https://doi.org/10.4143/crt.2019.122

Abstract PDF Supplementary Material PubReader ePub

Purpose
Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL).
Materials and Methods
Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL–International Prognostic Index (IPI) together with DM.
Results
The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLL-IPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI.
Conclusion
Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.

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Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
Yuchen Zhang, Anxin Li
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Pouya Goleij, Mohammad Amin Khazeei Tabari, Ahmed Rabie Dahab Ahmed, Leena Mohamed Elamin Mohamed, Ghaida Ahmed Hamed Saleh, Malak Tarig Mohamed Abdu Hassan, Alaa Galal Mohammed Moahmmednoor, Haroon Khan
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Rong Xu, Tingjin Zheng, Chaoqun Ouyang, Xiaoming Ding, Chenjin Ge
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Association between diabetes and acute lymphocytic leukemia, acute myeloid leukemia, non-Hopkin lymphoma, and multiple myeloma
Ji Zhong Zhao, Yu Cheng Lu, Yan Min Wang, Bo Lian Xiao, Hong Yan Li, Shao Chin Lee, Li Juan Wang
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Increased serum level of alpha-2 macroglobulin and its production by B-lymphocytes in chronic lymphocytic leukemia
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Frontiers in Immunology.2022;[Epub] CrossRef

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Albumin-to-Fibrinogen Ratio as an Independent Prognostic Parameter in Untreated Chronic Lymphocytic Leukemia: A Retrospective Study of 191 Cases: Yi-Xin Zou, Jia Qiao, Hua-Yuan Zhu, Rui-Nan Lu, Yi Xia, Lei Cao, Wei Wu, Hui Jin, Wen-Jie Liu, Jin-Hua Liang, Jia-Zhu Wu, Li Wang, Lei Fan, Wei Xu, Jian-Yong Li; Cancer Res Treat. 2019;51(2):664-671. Published online August 1, 2018; DOI: https://doi.org/10.4143/crt.2018.358

Abstract PDF PubReader ePub

Purpose
Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients.
Materials and Methods
In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients.
Results
The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70.
Conclusion
These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.

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NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia: Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo; Cancer Res Treat. 2018;50(3):872-882. Published online September 13, 2017; DOI: https://doi.org/10.4143/crt.2017.283

Abstract PDF PubReader ePub

Purpose
We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL).
Materials and Methods
Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated.
Results
A total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p < 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p < 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p < 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group.
Conclusion
NUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.

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NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China
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Fang Zhang, Gulbanur Amat, Yanjing Tang, Ru Chen, Xin Tian, Wenting Hu, Changcheng Chen, Shuhong Shen, Yangyang Xie
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The Effect of NUDT15, TPMT, APEX1, and ITPA Genetic Variations on Mercaptopurine Treatment of Pediatric Acute Lymphoblastic Leukemia
Jae Min Lee, Ye Jee Shim, Do-Hoon Kim, Nani Jung, Jung-Sook Ha
Children.2021; 8(3): 224. CrossRef
Pharmacogenomics in Pediatric Oncology: Mitigating Adverse Drug Reactions While Preserving Efficacy
Abdelbaset A. Elzagallaai, Bruce C. Carleton, Michael J. Rieder
Annual Review of Pharmacology and Toxicology.2021; 61(1): 679. CrossRef
DNA-thioguanine nucleotide as a treatment marker in acute lymphoblastic leukemia patients with NUDT15 variant genotypes
Hee Young Ju, Ji Won Lee, Hee Won Cho, Ju Kyung Hyun, Youngeun Ma, Eun Sang Yi, Keon Hee Yoo, Ki Woong Sung, Rihwa Choi, Hong Hoe Koo, Soo-Youn Lee, A. M. Abd El-Aty
PLOS ONE.2021; 16(1): e0245667. CrossRef
NUDT15: A bench to bedside success story
Ann M. Moyer
Clinical Biochemistry.2021; 92: 1. CrossRef
Association Between Genetic Polymorphisms of Metabolic Enzymes and Azathioprine-Induced Myelosuppression in 1,419 Chinese Patients: A Retrospective Study
Zhao-Yang Chen, Yang-Hui Zhu, Ling-Yan Zhou, Wei-Qiao Shi, Zhou Qin, Bin Wu, Yu Yan, Yu-Wen Pei, Ning-Ning Chao, Rui Zhang, Mi-Ye Wang, Ze-Hao Su, Xiao-Jun Lu, Zhi-Yao He, Ting Xu
Frontiers in Pharmacology.2021;[Epub] CrossRef
NUDT15 polymorphism in healthy children with Bai nationality in Yunnan of China
Gangling Pu, Yali Wang, Shaoqin Duan, Jingpei Chen, Chunhui Yang, Tingting Cui, Chunlian Fang, Yan Zhou, Han Zhang, Xin Tian
Pediatrics International.2021; 63(7): 790. CrossRef
Significance of TPMT and NUDT15 variants in 6-mercaptopurine metabolism in acute lymphoblastic leukaemia/lymphoma patients
E. S. Kotova, O. A. Gavrilina, A. B. Sudarikov
Russian journal of hematology and transfusiology.2021; 66(2): 253. CrossRef
NUDT15 c.415C>T Polymorphism Predicts 6-MP Induced Early Myelotoxicity in Patients with Acute Lymphoblastic Leukemia Undergoing Maintenance Therapy
Aswin Anand Pai, Ajith Mohan, Esther Sathya Bama Benjamin, Raveen Stephen Stallon Illangeswaran, Infencia Xavier Raj, Nancy Beryl Janet, Arun Kumar Arunachalam, ML Kavitha, Uday Kulkarni, Anup J Devasia, NA Fouzia, Aby Abraham, Alok Srivastava, Biju Georg
Pharmacogenomics and Personalized Medicine.2021; Volume 14: 1303. CrossRef
Reducing risk in thiopurine therapy
Anthony M. Marinaki, Monica Arenas-Hernandez
Xenobiotica.2020; 50(1): 101. CrossRef
Precision therapy of 6‐mercaptopurine in Chinese children with acute lymphoblastic leukaemia
Yue Zhou, Li Wang, Xiao‐Ying Zhai, Li Wen, Fang Tang, Fan Yang, Xi‐Ting Liu, Lei Dong, Li‐Juan Zhi, Hai‐Yan Shi, Guo‐Xiang Hao, Yi Zheng, Evelyne Jacqz‐Aigrain, Tian‐You Wang, Wei Zhao
British Journal of Clinical Pharmacology.2020; 86(8): 1519. CrossRef
NUDT15 Genetic Variants are Related to Thiopurine-Induced Neutropenia in Thai Children with Acute Lymphoblastic Leukemia
Apichaya Puangpetch, Rawiporn Tiyasirichokchai, Samart Pakakasama, Supaporn Wiwattanakul, Usanarat Anurathapan, Suradej Hongeng, Chonlaphat Sukasem
Pharmacogenomics.2020; 21(6): 403. CrossRef
Association of NUDT15 c.415C>T and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia
Sunitha Kodidela, Patchava Dorababu, Dimpal N. Thakkar, Biswajit Dubashi, Rajan Sundaram, Niveditha Muralidharan, Ravi Prasad Nidanapu, Anil Aribandi, Suresh Chandra Pradhan, Chakradhara Rao Satyanarayana Uppugunduri
Genes.2020; 11(6): 594. CrossRef
Classification and regression tree-based prediction of 6-mercaptopurine-induced leucopenia grades in children with acute lymphoblastic leukemia
Shaik Mohammad Naushad, Patchava Dorababu, Yedluri Rupasree, Addepalli Pavani, Digumarti Raghunadharao, Tajamul Hussain, Salman A. Alrokayan, Vijay Kumar Kutala
Cancer Chemotherapy and Pharmacology.2019; 83(5): 875. CrossRef
Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia
Rihwa Choi, Insuk Sohn, Min‐Ji Kim, Hye In Woo, Ji Won Lee, Youngeun Ma, Eun Sang Yi, Hong Hoe Koo, Soo‐Youn Lee
British Journal of Clinical Pharmacology.2019; 85(7): 1585. CrossRef
Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients
Xia Zhu, Kang Chao, Miao Li, Wen Xie, Hong Zheng, Jin-Xin Zhang, Pin-Jin Hu, Min Huang, Xiang Gao, Xue-Ding Wang
World Journal of Gastroenterology.2019; 25(38): 5850. CrossRef
Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report
Juan Cheng, Hao Zhang, Hai‑Zhen Ma, Juan Li
Experimental and Therapeutic Medicine.2019;[Epub] CrossRef
Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping
Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa
Journal of Gastroenterology.2018; 53(2): 172. CrossRef

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APEX1 Polymorphism and Mercaptopurine-Related Early Onset Neutropenia in Pediatric Acute Lymphoblastic Leukemia: Hyery Kim, Heewon Seo, Yoomi Park, Byung-Joo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Ju Han Kim, Hyoung Jin Kang; Cancer Res Treat. 2018;50(3):823-834. Published online September 4, 2017; DOI: https://doi.org/10.4143/crt.2017.351

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients.
Materials and Methods
Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients.
Results
Using bioinformatics tools and genetic data, four functionally interesting variants were selected (ABCC4, APEX1, CYP1A1, and CYP4F2). Including four variants, 23 variants in 12 genes potentially linked to MP adverse reactions were selected as final candidates for subsequent analysis in 185 patients. Ultimately, a variant allele in APEX1 rs2307486was found to be strongly associated with MP-induced neutropenia that occurred within 28 days of initiating MP (odds ratio, 3.44; p=0.02). Moreover, the cumulative incidence of MP-related neutropenia was significantly higher in patients with APEX1 rs2307486 variants, as GG genotypes were associated with the highest cumulative incidence (p < 0.01). NUDT15 rs116855232 variants were strongly associated with a higher cumulative incidence of neutropenia (p < 0.01), and a lower median dose of tolerated MP throughout maintenance treatment (p < 0.01).
Conclusion
We have identified that APEX1 rs2307486 variants conferred an increased risk of MP-related early onset neutropenia. APEX1 and NUDT15 both contribute to cell protection from DNA damage or misincorporation, so alleles that impair the function of either gene may affect MP sensitivities, thereby inducing MP-related neutropenia.

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Parallel Toxicities: A Comparative Analysis of Chemotherapy-Induced Neutropenia and Alopecia
Simonetta I. Gaumond, Karen J. Lee, Peyton V. Warp, Isabella Kamholtz, Emilee M. Dreifus, Joaquin J. Jimenez
Cancers.2025; 17(7): 1163. CrossRef
Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
Ashwin Kamath, Suresh Kumar Srinivasamurthy, Mukta N. Chowta, Sheetal D. Ullal, Youssef Daali, Uppugunduri S. Chakradhara Rao
Pharmaceuticals.2022; 15(8): 990. CrossRef
The Effect of NUDT15, TPMT, APEX1, and ITPA Genetic Variations on Mercaptopurine Treatment of Pediatric Acute Lymphoblastic Leukemia
Jae Min Lee, Ye Jee Shim, Do-Hoon Kim, Nani Jung, Jung-Sook Ha
Children.2021; 8(3): 224. CrossRef
Interplay between IL6 and CRIM1 in thiopurine intolerance due to hematological toxicity in leukemic patients with wild-type NUDT15 and TPMT
Hyery Kim, Seungwon You, Yoomi Park, Jung Yoon Choi, Youngeun Ma, Kyung Tak Hong, Kyung-Nam Koh, Sunmin Yun, Kye Hwa Lee, Hee Young Shin, Suehyun Lee, Keon Hee Yoo, Ho Joon Im, Hyoung Jin Kang, Ju Han Kim
Scientific Reports.2021;[Epub] CrossRef
NUDT15 polymorphism in healthy children with Bai nationality in Yunnan of China
Gangling Pu, Yali Wang, Shaoqin Duan, Jingpei Chen, Chunhui Yang, Tingting Cui, Chunlian Fang, Yan Zhou, Han Zhang, Xin Tian
Pediatrics International.2021; 63(7): 790. CrossRef
A Dual Face of APE1 in the Maintenance of Genetic Stability in Monocytes: An Overview of the Current Status and Future Perspectives
Gabriela Betlej, Ewelina Bator, Antoni Pyrkosz, Aleksandra Kwiatkowska
Genes.2020; 11(6): 643. CrossRef
Homozygote CRIM1 variant is associated with thiopurine-induced neutropenia in leukemic patients with both wildtype NUDT15 and TPMT
Yoomi Park, Hyery Kim, Heewon Seo, Jung Yoon Choi, Youngeun Ma, Sunmin Yun, Byung-Joo Min, Myung-Eui Seo, Keon Hee Yoo, Hyoung Jin Kang, Ho Joon Im, Ju Han Kim
Journal of Translational Medicine.2020;[Epub] CrossRef
Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology
Emma C. Bernsen, Melanie M. Hagleitner, Theodorus W. Kouwenberg, Lidwien M. Hanff
Frontiers in Pharmacology.2020;[Epub] CrossRef
Long-term treatment outcomes of children and adolescents with lymphoblastic lymphoma treated with various regimens: a single-center analysis
Ho Jung Choi, Juhee Shin, Sunghan Kang, Jin Kyung Suh, Hyery Kim, Kyung-Nam Koh, Ho Joon Im
BLOOD RESEARCH.2020; 55(4): 262. CrossRef
NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia
Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo
Cancer Research and Treatment.2018; 50(3): 872. CrossRef

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p15^Ink4b Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients: Shahid M. Baba, Niyaz A. Azad, Zafar A. Shah, Dil-Afroze , Arshad A. Pandith, Aleem Jan, Sheikh A. Aziz; Cancer Res Treat. 2017;49(3):790-797. Published online December 5, 2016; DOI: https://doi.org/10.4143/crt.2016.108

Abstract PDF PubReader ePub

Purpose
The p15^Ink4b gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir(North India).
Materials and Methods
p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction,while its subsequent expression analysiswas carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).
Results
Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA.
Conclusion
Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

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Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation
Miao Zhang, Jia-yi Zhang, Ming-qian Sun, Peng Lu, Jian-xun Liu
Chinese Journal of Integrative Medicine.2022; 28(3): 281. CrossRef
A study on DNA methylation status in promoter region of p15 gene in patients of acute myeloid leukemia and myelodysplastic syndrome
Sangeetha Sampath, Pratibha Misra, Sandeep Kumar Yadav, Sanjeevan Sharma, Venkatesan Somasundaram
Medical Journal Armed Forces India.2021; 77(3): 337. CrossRef
Gene regulations and delivery vectors for treatment of cancer
Ming Chen, Yu-Xin Ren, Ying Xie, Wan-Liang Lu
Journal of Pharmaceutical Investigation.2020; 50(3): 309. CrossRef
SERS-Based Assessment of MRD in Acute Promyelocytic Leukemia?
Cristina Turcas, Vlad Moisoiu, Andrei Stefancu, Ancuta Jurj, Stefania D. Iancu, Patric Teodorescu, Sergiu Pasca, Anca Bojan, Adrian Trifa, Sabina Iluta, Alina-Andreea Zimta, Bobe Petrushev, Mihnea Zdrenghea, Horia Bumbea, Daniel Coriu, Delia Dima, Nicolae
Frontiers in Oncology.2020;[Epub] CrossRef
Clinical and prognostic effects ofCDKN2A,CDKN2BandCDH13promoter methylation in ovarian cancer: a study using meta-analysis and TCGA data
Liang Xia, Wenzhu Zhang, Li Gao
Biomarkers.2019; 24(7): 700. CrossRef
Higher satisfaction with an alternative collection device for stool sampling in colorectal cancer screening with fecal immunochemical test: a cross-sectional study
Hye Young Shin, Mina Suh, Kui Son Choi, Sang-Hyun Hwang, Jae Kwan Jun, Dong Soo Han, You Kyoung Lee, Jae Hwan Oh, Chan Wha Lee, Do-Hoon Lee
BMC Cancer.2018;[Epub] CrossRef
Aging- and Senescence-associated Changes of Mesenchymal Stromal Cells in Myelodysplastic Syndromes
Domenico Mattiucci, Giulia Maurizi, Pietro Leoni, Antonella Poloni
Cell Transplantation.2018; 27(5): 754. CrossRef
The interaction between DNA methylation and long non‐coding RNA during the onset of puberty in goats
Chen Yang, Xiaoxiao Gao, Jing Ye, Jianping Ding, Ya Liu, Hongyu Liu, Xiumei Li, Yunhai Zhang, Jie Zhou, Weiping Huang, Fugui Fang, Yinghui Ling
Reproduction in Domestic Animals.2018; 53(6): 1287. CrossRef

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Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea: Jae Wook Lee, Seong-koo Kim, Pil-Sang Jang, Nack-Gyun Chung, Dae-Chul Jeong, Myungshin Kim, Bin Cho, Hack-Ki Kim; Cancer Res Treat. 2017;49(2):446-453. Published online August 10, 2016; DOI: https://doi.org/10.4143/crt.2016.211

Abstract PDF Supplementary Material PubReader ePub

Purpose
ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables.
Materials and Methods
Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities.
Results
The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%.
Conclusion
ETV6/RUNX1 ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end ofremission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.

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Genetic Profiling of Acute and Chronic Leukemia via Next-Generation Sequencing: Current Insights and Future Perspectives
Laras Pratiwi, Fawzia Hanum Mashudi, Mukti Citra Ningtyas, Henry Sutanto, Pradana Zaky Romadhon
Hematology Reports.2025; 17(2): 18. CrossRef
Outcome and Prognostic Factors of Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Relapsed or Refractory ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia
Guan-hua Hu, Xiao-hui Zhang, Kai-yan Liu, Lan-ping Xu, Yu Wang, Yi-fei Cheng, Xiao-jun Huang
Acta Haematologica.2024; 147(5): 534. CrossRef
Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia
Jae Wook Lee, Seongkoo Kim, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho
Cancer Research and Treatment.2021; 53(2): 567. CrossRef
Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group
Kun-yin Qiu, Hong-gui Xu, Xue-qun Luo, Hui-rong Mai, Ning Liao, Li-hua Yang, Min-cui Zheng, Wu-qing Wan, Xue-dong Wu, Ri-yang Liu, Qi-wen Chen, Hui-qin Chen, Xiao-fei Sun, Hua Jiang, Xing-jiang Long, Guo-hua Chen, Xin-yu Li, Chang-gang Li, Li-bin Huang, Y
Frontiers in Oncology.2021;[Epub] CrossRef
ETV6/RUNX1-positive childhood acute lymphoblastic leukemia in China: excellent prognosis with improved BFM protocol
Yu Wang, Hui-min Zeng, Le-ping Zhang
Italian Journal of Pediatrics.2018;[Epub] CrossRef
Prognostic factors and treatment of pediatric acute lymphoblastic leukemia
Jae Wook Lee, Bin Cho
Korean Journal of Pediatrics.2017; 60(5): 129. CrossRef
ETV6 and ETV7: Siblings in hematopoiesis and its disruption in disease
Parisa Rasighaemi, Alister C. Ward
Critical Reviews in Oncology/Hematology.2017; 116: 106. CrossRef
Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse
Congcong Sun, Lixian Chang, Xiaofan Zhu
Oncotarget.2017; 8(21): 35445. CrossRef

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Case Report

Progressive Multifocal Leukoencephalopathy after Ibrutinib Therapy for Chronic Lymphocytic Leukemia: Mathias Lutz, Arik B. Schulze, Elisabeth Rebber, Stefanie Wiebe, Tarek Zoubi, Oliver M. Grauer, Torsten Keßler, Andrea Kerkhoff, Georg Lenz, Wolfgang E. Berdel; Cancer Res Treat. 2017;49(2):548-552. Published online July 12, 2016; DOI: https://doi.org/10.4143/crt.2016.110

Abstract PDF PubReader ePub

Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton’s tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.

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Akito Funatsu, Kazuo Nakamichi, Midori Araki, Tetsuya Fukumoto, Hideki Mine
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Larissa Lane Cardoso Teixeira, Viviane Regina Hernandez Nunes, Guilherme Fleury Perini, Carolina Cristina Pellegrino Feres, Danielle Ovigli, Nelson Hamerschlak
Hematology, Transfusion and Cell Therapy.2022; 44(3): 437. CrossRef
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F. Tahir, J. Sy, S. Reddel, J. Trotman
Leukemia & Lymphoma.2022; 63(6): 1464. CrossRef
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Tuğba Çetintepe, Füsun Gediz, Işın Akyar, Lutfi Çetintepe, Ali Murat Koç
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Sarah D’Alessandro, Diletta Scaccabarozzi, Lucia Signorini, Federica Perego, Denise P. Ilboudo, Pasquale Ferrante, Serena Delbue
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Case Report

Reversible Pulmonary Arterial Hypertension Associated with Dasatinib for Chronic Myeloid Leukemia: Ji Hyung Hong, Sung-Eun Lee, Soo Young Choi, Soo-Hyun Kim, Eun-Jung Jang, Ju-Hee Bang, Jin Eok Park, Hye-Rim Jeon, Yun Jeong Oh, Jeong-Eun Yi, Hae Ok Jung, Ho Joong Youn, Dong-Wook Kim; Cancer Res Treat. 2015;47(4):937-942. Published online November 17, 2014; DOI: https://doi.org/10.4143/crt.2013.155

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We describe two cases of pulmonary arterial hypertension (PAH) that occurred under dasatinib treatment and were resolved after dasatinib discontinuation. Two patients with chronic phase chronic myeloid leukemia (CML) were switched to dasatinib therapy because of hematological progress while receiving imatinib. These patients had New York Heart Association (NYHA) functional class II dyspnea with elevated right ventricular systolic pressure (RVSP), which progressed under dasatinib treatment. After dasatinib treatment was discontinued, subjective symptoms were improved to NYHA functional class I and the follow-up transthoracic Doppler echocardiography showed improved RVSP. Treatment with an alternate tyrosine kinase inhibitor was initiated and had been continued without development of dyspnea or elevation of RVSP. This report suggests that dasatinib can cause the reversible PAH, therefore, routine cardiopulmonary evaluation before and during treatment with dasatinib may be needed in CML patients with clinical manifestations.

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Prevalence and predictors of pulmonary hypertension in patients with myeloproliferative neoplasms: single-center study
Mohamed Eid, Ali M Kasem, Yasser M Kamal, Mahmoud Hamdy, Mahmoud Gaber
The Egyptian Journal of Haematology.2024; 49(1): 45. CrossRef
Relationship between Dasatinib-induced Pulmonary Hypertension and Drug Dose
Kana Kubota, Yasushi Imai, Iekuni Oh, Shuichi Ueno, Yoshinobu Kanda, Kazuomi Kario
Internal Medicine.2022; 61(15): 2263. CrossRef
Change of right ventricular systolic pressure can indicate dasatinib‐induced pulmonary arterial hypertension in chronic myeloid leukemia
Sung‐Eun Lee, Jee Hyun Kong, Soo‐Hyun Kim, Eun‐Jung Jang, Nack‐Gyun Chung, Bin Cho, Suk Joong Oh, Hae‐Eok Jung, Ho‐Joong Youn, Woo‐Baek Chung, Dong‐Wook Kim
Cancer Medicine.2021; 10(5): 1515. CrossRef
mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target
Aleksandra Babicheva, Ayako Makino, Jason X.-J. Yuan
International Journal of Molecular Sciences.2021; 22(4): 2144. CrossRef
Dasatinib-Induced Pulmonary Arterial Hypertension: A Case Report
Ru Liu, Yinjiang Tang, Ting Fu, Jianli Zhou, Lijiao Ma, Jinqing Yuan, Ou Xu
Research Reports in Clinical Cardiology.2021; Volume 12: 33. CrossRef
Pulmonary hypertension in patients with chronic myeloid leukemia
Ik-Chan Song, Sang-Hoon Yeon, Myeong-Won Lee, Hyewon Ryu, Hyo-Jin Lee, Hwan-Jung Yun, Byung Joo Sun, Jae-Hyeong Park, Jin-Ok Jeong, Deog-Yeon Jo
Medicine.2021; 100(33): e26975. CrossRef
A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities
Zahra Nekoukar, Minoo Moghimi, Ebrahim Salehifar
BLOOD RESEARCH.2021; 56(4): 229. CrossRef
Dasatinib-induced pulmonary arterial hypertension complicated with scleroderma: a case report
Takumi Toya, Yuji Nagatomo, Kazuki Kagami, Takeshi Adachi, Julia Grapsa, Julia Grapsa, Hatem Soliman Aboumarie, Amir Aziz, Peysh A Patel
European Heart Journal - Case Reports.2019;[Epub] CrossRef
Dasatinib‐induced pulmonary arterial hypertension
Nurgül Özgür Yurttaş, Ahmet Emre Eşkazan
British Journal of Clinical Pharmacology.2018; 84(5): 835. CrossRef
Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib
Mariko Minami, Takeshi Arita, Hiromi Iwasaki, Tsuyoshi Muta, Takatoshi Aoki, Kenichi Aoki, Satoshi Yamasaki, Takamitsu Matsushima, Koji Kato, Katsuto Takenaka, Kazuki Tanimoto, Tomohiko Kamimura, Ryosuke Ogawa, Koichi Akashi, Toshihiro Miyamoto
British Journal of Haematology.2017; 177(4): 578. CrossRef
Combination targeted pulmonary hypertension therapy in the resolution of Dasatinib‐associated pulmonary arterial hypertension
Arun Jose, Hind Rafei, Jalil Ahari
Pulmonary Circulation.2017; 7(4): 803. CrossRef
Pulmonary arterial hypertension in a patient treated with dasatinib: a case report
Andris Skride, Matiss Sablinskis, Kristaps Sablinskis, Krista Lesina, Aivars Lejnieks, Sandra Lejniece
Journal of Medical Case Reports.2017;[Epub] CrossRef
Pulmonary arterial hypertension in congenital heart disease: translational opportunities to study the reversibility of pulmonary vascular disease
Diederik E. van der Feen, B. Bartelds, Rudolf A. de Boer, Rolf M.F. Berger
European Heart Journal.2017; 38(26): 2034. CrossRef
Dasatinib

Reactions Weekly.2015; 1580(1): 136. CrossRef
Deletion of Src family kinase Lyn aggravates endotoxin-induced lung inflammation
Rong Gao, Zhongsen Ma, Mengshi Ma, Jinyan Yu, Jiao Chen, Zhenyu Li, Sreerama Shetty, Jian Fu
American Journal of Physiology-Lung Cellular and Molecular Physiology.2015; 309(11): L1376. CrossRef

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Case Report

Long-Term Survival after T-cell Lymphoblastic Lymphoma Treated with One Cycle of Hyper-CVAD Regimen: Il Hwan Ryu, In Sung Cho, Ah Jeong Ryu, Min Gyu Kim, Jae Woong Jeon, Joo Seok Kim, Jae Joon Lee, Ji Wook Choi, Dong Wook Kang; Cancer Res Treat. 2015;47(1):115-119. Published online August 25, 2014; DOI: https://doi.org/10.4143/crt.2013.122

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T-lymphoblastic lymphoma (T-LBL) is a rare form of aggressive non-Hodgkin’s lymphoma. The standard approach for management of T-LBL involves intensive multiagent chemotherapy regimens for induction and consolidation phases with central nervous system prophylaxis and a maintenance phase lasting 12-18 months. We report on a case of long-term survival after one cycle of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and high-dose methotrexate. A 30-year-old woman diagnosed with T-LBL with a large mediastinal mass underwent one cycle of hyper-CVAD. Four days after the start of treatment, the mediastinal mass was markedly reduced. Treatment continued with one cycle of consolidation chemotherapy, comprising high-dose methotrexate and high-dose cytarabine. The patient then refused all further chemotherapeutic treatment. Seven years have passed without relapse.

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An aberrant presentation of non-hodgkin’s lymphoma as pus: A curious journey
Mayur Devraj, Chaitanya Kappagantu, Sushma Dugad, Ravidra Shinde, Komal Shah
IP Indian Journal of Immunology and Respiratory Medicine.2023; 7(4): 173. CrossRef
The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies – A Narrative Review

Paulina Stefaniuk, Agnieszka Szymczyk, Monika Podhorecka
Cancer Management and Research.2020; Volume 12: 2961. CrossRef
T-cell lymphoblastic lymphoma involving the ocular adnexa: report of two cases and review of the current literature
Lucy Sun, Alan H. Friedman, Rand Rodgers, Matthew Schear, Giovanni Greaves, Kathryn B. Freidl
Orbit.2019; 38(5): 412. CrossRef
Effectiveness of modified hyper‐CVAD chemotherapy regimen in the treatment of adult acute lymphoblastic leukemia: a retrospective experience
Hasan Jalaeikhoo, Mohsen Rajaeinejad, Manoutchehr Keyhani, Mohammad Zokaasadi, Mohammad Mehdi Dehghani Firoozabadi
Cancer Medicine.2018; 7(3): 594. CrossRef

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Original Article

Src Family Kinase Inhibitor PP2 Has Different Effects on All-Trans-Retinoic Acid or Arsenic Trioxide-Induced Differentiation of an Acute Promyelocytic Leukemia Cell Line: Suk-Gu Yoon, Hee-Jeong Cheong, Sook-Ja Kim, Kyoung Ha Kim, Sang-Cheol Lee, Namsu Lee, Hee Sook Park, Jong-Ho Won; Cancer Res Treat. 2013;45(2):126-133. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.126

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PURPOSE
Leukemic promyelocytes have the unique ability to undergo differentiation after exposure to retinoic acid and both differentiation and apoptosis after exposure to arsenic trioxide (ATO). Recent studies have shown that inhibition of Src family kinases (SFKs) resulted in enhancement of retinoic acid-induced myeloid differentiation.
MATERIALS AND METHODS
In this study, we investigated the question of whether the SFK inhibitor PP2 enhanced the differentiation of NB4 cells when combined with ATO as well as when combined with all-trans-retinoic acid (ATRA). In addition, we attempted to determine the difference in retinoic acid-induced gene expression between cells treated with PP2 in combination with ATRA and in combination with ATO.
RESULTS
SFK inhibitor PP2 induced significant enhancement of ATRA- or ATO-induced differentiation of NB4 cells. A significantly stronger synergistic effect was observed when PP2 was combined with ATRA than when combined with ATO. Flow cytometric analysis demonstrated a significant increase in CD11b-positive granulocytes up to 60.73% and 31.58%, respectively. These results were confirmed by nitroblue tetrazolium staining. These effects were not related to apoptosis. Results of Annexin-V-fluorescein staining revealed that PP2 combined with ATRA or PP2 combined with ATO did not induce apoptosis in NB4 cells. Retinoic acid-induced gene expression was different in both groups. Intercellular adhesion molecule-1 expression showed a significant increase in cells treated with PP2 in combination with ATRA, whereas cathepsin D expression showed a significant increase in cells treated with PP2 in combination with ATO.
CONCLUSION
Our data showed that SFK inhibitor PP2 enhanced acute promyelocytic leukemia cell differentiation when combined with either ATRA or ATO with difference in activation of retinoic acid-induced genes.

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An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications
Yanan Jiang, Xiuyun Shen, Fengnan Zhi, Zhengchao Wen, Yang Gao, Juan Xu, Baofeng Yang, Yunlong Bai
Cell Death Discovery.2023;[Epub] CrossRef
Integrated bioinformatics analysis and network pharmacology to explore the potential mechanism of Patrinia heterophylla Bunge against acute promyelocytic leukemia
Liya Feng, Sha Zhu, Jian Ma, Yali Hong, Meixia Wan, Qian Qiu, Hongjing Li, Juan Li
Medicine.2023; 102(40): e35151. CrossRef
Serum levels of FAK and some of its effectors in adult AML: correlation with prognostic factors and survival
Mona G. El-Sisi, Sara M. Radwan, Alia M. Saeed, Hala O. El-Mesallamy
Molecular and Cellular Biochemistry.2021; 476(5): 1949. CrossRef
O-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis
Zhen Zhang, Matthew P. Parker, Stefan Graw, Lesya V. Novikova, Halyna Fedosyuk, Joseph D. Fontes, Devin C. Koestler, Kenneth R. Peterson, Chad Slawson
Journal of Biological Chemistry.2019; 294(4): 1363. CrossRef
Src family kinases and their role in hematological malignancies
Matthew Ku, Meaghan Wall, Ruth N. MacKinnon, Carl R. Walkley, Louise E. Purton, Constantine Tam, David Izon, Lynda Campbell, Heung-Chin Cheng, Harshal Nandurkar
Leukemia & Lymphoma.2015; 56(3): 577. CrossRef
Hematopoietic cell kinase (HCK) as a therapeutic target in immune and cancer cells
Ashleigh R. Poh, Robert J.J. O’Donoghue, Matthias Ernst
Oncotarget.2015; 6(18): 15752. CrossRef
Src family kinase inhibitor PP2 enhances differentiation of acute promyelocytic leukemia cell line induced by combination of all-trans-retinoic acid and arsenic trioxide
Yun Seok Jung, Hee-Jeong Cheong, Sook-Ja Kim, Kyoung Ha Kim, Namsu Lee, Hee Sook Park, Jong-Ho Won
Leukemia Research.2014; 38(8): 977. CrossRef

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Case Report

Second Primary Glioblastoma Multiforme Following Autologous Hematopoietic Stem Cell Transplantation in a Patient with Acute Myelogenous Leukemia: Eun-Oh Kim, Hee-Je Kim, Ki-Seong Eom, Byung-Sik Cho, Sung-Eun Lee, Seung-Ah Yahng, Jong-Wook Lee, Woo-Sung Min; Cancer Res Treat. 2011;43(3):195-198. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.195

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Glioblastoma multiforme (GM) is one of the most aggressive primary brain tumors, and has a poor prognosis despite intensive treatment. GM is also the most malignant astrocytoma, with histopathological features that include cellular polymorphism, rapid mitotic activity, microvascular proliferation, and necrosis. The causes of GM remain obscure, but several reports have shown associations between GM and genetic alterations and radiation exposure. Furthermore, high-dose chemotherapy/radiotherapy with autologous stem cell transplantation is increasingly being used to treat patients with leukemia, and patients who undergo stem cell transplantation have a higher risk of solid tumor cancer development later in life. Based on these associations, we discuss GM development in a patient who underwent chemoradiotherapy conditioning prior to stem cell transplantation.

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Glioblastoma Multiforme in a Post Allogeneic Stem Cell Transplant Patient. A Case Report and Literature Review of Post Transplant Neurological Tumors
Abhijeet P. Ganapule, Sunita Susan Varghese, Geeta Chacko, I. Aparna, Auro Viswabandya
Indian Journal of Hematology and Blood Transfusion.2016; 32(S1): 192. CrossRef

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1 Crossref

Original Article

Bcl-2 as a Predictive Factor for Biochemical Recurrence after Radical Prostatectomy: An Interim Analysis: In-Chang Cho, Han Soo Chung, Kang Su Cho, Jeong Eun Kim, Jae Young Joung, Ho Kyung Seo, Jinsoo Chung, Weon Seo Park, Eun Kyung Hong, Kang Hyun Lee; Cancer Res Treat. 2010;42(3):157-162. Published online September 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.3.157

Abstract PDF PubReader ePub

Purpose

The objective of this study was to determine Bcl-2 expression in localized prostate cancer and its potential role as a predictive factor for biochemical recurrence (BCR).

Materials and Methods

This study included 171 Korean patients with newly diagnosed adenocarcinoma of the prostate who underwent radical prostatectomy (RP) without neoadjuvant therapy at a single center between February 2005 and May 2009. RP specimens obtained from these patients were analyzed for the expression of Bcl-2 using tissue microarray. The values of Bcl-2 and other clinicopathologic factors were evaluated. Statistical analysis was performed with contingency table analysis, chi-square tests, and a Cox proportional hazard model.

Results

Bcl-2 expression was immunohistologically-confirmed in 42 patients (24.6%). Bcl-2 expression was not associated with conventional clinicopathologic factors. Bcl-2 negative patients had a significantly longer mean BCR-free survival than Bcl-2-positive patients (p=0.036). Among several variables, a high Gleason score in the RP specimen (≥8), extraprostatic extension, seminal vesicle invasion (SVI), lymphovascular invasion (LVI), and Bcl-2 expression were significant predictors of BCR based on univariate analysis. Multivariate Cox proportional hazards analysis revealed that BCR was significantly associated with a high prostate specific antigen level (p=0.047), SVI (p<0.001), a positive surgical margin (p=0.004) and Bcl-2 expression (p=0.012).

Conclusion

Bcl-2 expression in RP specimens is associated with a significantly worse outcome, suggesting a potential clinical role for Bcl-2. Post-operative Bcl-2 could be a significant predictor of outcome after RP.

Citations

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Association of Lymphovascular Invasion with Biochemical Recurrence and Adverse Pathological Characteristics of Prostate Cancer: A Systematic Review and Meta-analysis
Jakub Karwacki, Marcel Stodolak, Andrzej Dłubak, Łukasz Nowak, Adam Gurwin, Kamil Kowalczyk, Paweł Kiełb, Nazar Holdun, Wojciech Szlasa, Wojciech Krajewski, Agnieszka Hałoń, Anna Karwacka, Tomasz Szydełko, Bartosz Małkiewicz
European Urology Open Science.2024; 69: 112. CrossRef
Immunohistochemical Expression of MDM2, Bcl-2, SATB2 and Ki-67 in Histological Variants of Unicystic Ameloblastoma
Koustubh Amol Surana, Deepak Pandiar, Reshma Poothakulath Krishnan
Head and Neck Pathology.2024;[Epub] CrossRef
Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer
Daniel Westaby, Juan M. Jimenez-Vacas, Ana Padilha, Andreas Varkaris, Steven P. Balk, Johann S. de Bono, Adam Sharp
Cancers.2021; 14(1): 51. CrossRef
miR-205: A Potential Biomedicine for Cancer Therapy
Neeraj Chauhan, Anupam Dhasmana, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu
Cells.2020; 9(9): 1957. CrossRef
Bcl‐2 is a prognostic marker and its silencing inhibits recurrence in ameloblastomas
Jue Young Kim, Jinsun Kim, Shadavlonjid Bazarsad, In‐Ho Cha, Sung‐Won Cho, Jin Kim
Oral Diseases.2019; 25(4): 1158. CrossRef
Tumor-Specific Induction of the Intrinsic Apoptotic Pathway—A New Therapeutic Option for Advanced Prostate Cancer?
Philipp Wolf
Frontiers in Oncology.2019;[Epub] CrossRef
PI3K pathway and Bcl-2 family. Clinicopathological features in prostate cancer
Norelia Torrealba, Gonzalo Rodriguez-Berriguete, Benito Fraile, Gabriel Olmedilla, Pilar Martínez-Onsurbe, Manuel Sánchez-Chapado, Ricardo Paniagua, Mar Royuela
The Aging Male.2018; 21(3): 211. CrossRef
Positive surgical margin is associated with biochemical recurrence risk following radical prostatectomy: a meta-analysis from high-quality retrospective cohort studies
Lijin Zhang, Bin Wu, Zhenlei Zha, Hu Zhao, Yuefang Jiang, Jun Yuan
World Journal of Surgical Oncology.2018;[Epub] CrossRef
The impact of lymphovascular invasion in patients with prostate cancer following radical prostatectomy and its association with their clinicopathological features
Wei Jiang, Lijin Zhang, Bin Wu, Zhenlei Zha, Hu Zhao, Yuan Jun, Yuefang Jiang
Medicine.2018; 97(49): e13537. CrossRef
Bcl2 en cáncer avanzado de próstata y asociación con resistencia a la castración
R.F. Velázquez-Macías, F.E. De La Torre-Rendón, G. Ramos-Rodríguez, C.A. Calzada-Mendoza, R.M. Coral-Vázquez
Revista Mexicana de Urología.2016; 76(5): 288. CrossRef
Application of a new technique, spiral tissue microarrays constructed using needle biopsy specimens, to prostate cancer research
AKIRA KOMIYA, TOMONORI KATO, TAKASHI HORI, JUNYA FUKUOKA, KENJI YASUDA, HIDEKI FUSE
International Journal of Oncology.2014; 44(1): 195. CrossRef
MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer
BERLINDA VERDOODT, MATTHIAS NEID, MARKUS VOGT, VIKTORIA KUHN, SVEN-THORSTEN LIFFERS, REIN-JÜRI PALISAAR, JOACHIM NOLDUS, ANDREA TANNAPFEL, ALIREZA MIRMOHAMMADSADEGH
International Journal of Oncology.2013; 43(1): 307. CrossRef

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Case Report

Staphylococcal Endocarditis Presenting with a Renal Infarct in a Patient with Acute Lymphoblastic Leukemia: Meong Hi Son, Eun Sil Park, Ji-Hyun Seo, Jae-Young Lim, Chan-Hoo Park, Hyang-Ok Woo, Hee-Shang Youn; Cancer Res Treat. 2008;40(3):151-154. Published online September 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.3.151

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We present here a patient with acute lymphoblastic leukemia (ALL) and who developed infective endocarditis during induction chemotherapy with prednisolone, L-asparaginase (Leunase®), vincristine and adriamycin. The patient did not have a history of a central venous catheter. Sharp flank pain and fever occurred on the 25^th day of induction chemotherapy. In addition, a renal infarct and movable vegetations on the mitral valve were detected on the abdominal computed tomography (CT) and echocardiography. S. aureus was identified in the cultured blood. While the patient achieved remission, follow-up echocardiography revealed the vegetation had increased in size and an abscess pocket had developed despite the antibiotics and heparin therapy. Consequently, ten days after the diagnosis of infective endocarditis, a successful mitral valvuloplasty was performed without complications. The patient is currently on maintenance chemotherapy while in remission.

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Acute Lymphoblastic Leukemia with Infective Endocarditis Presented with Unusual Intracardiac Mass
Ali Sadeghpour Tabaei, Leili Koochakzadeh, Mohammadrafie Khorgami, Sepehr Sadeghpour Tabaei
Case Reports in Cardiology.2017; 2017: 1. CrossRef
Infective endocarditis presenting with loin pain: Table 1
Ali Kohansal, Valerie A Luyckx
BMJ Case Reports.2011; 2011: bcr0720103189. CrossRef

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Original Articles

Optimization and Limitation of Calcium Ionophore to Generate DCs from Acute Myeloid Leukemic Cells: Thanh-Nhan Nguyen Pham, Bo-Hwa Choi, Hyun-Kyu Kang, Chun-Chi Jin, Nguyen Hoang Tuyet Minh, Sang-Ki Kim, Jong-Hee Nam, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Ik-Joo Chung, Je-Jung Lee; Cancer Res Treat. 2007;39(4):175-180. Published online December 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.4.175

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Purpose

Calcium ionophore (CI) is used to generate dendritic cells (DCs) from progenitor cells, monocytes, or leukemic cells. The aim of this study was to determine the optimal dose of CI and the appropriate length of cell culture required for acute myeloid leukemia (AML) cells and to evaluate the limitations associated with CI.

Materials and Methods

To generate leukemic DCs, leukemic cells (4×10⁶ cells) from six AML patients were cultured with various concentrations of CI and/or IL-4 for 1, 2 or 3 days.

Results

Potent leukemic DCs were successfully generated from all AML patients, with an average number of 1.2×10⁶ cells produced in the presence of CI (270 ng/ml) for 2 days. Several surface molecules were clearly upregulated in AML cells supplemented with CI and IL-4, but not CD11c. Leukemic DCs cultured with CI had a higher allogeneic T cell stimulatory capacity than untreated AML cells, but the addition of IL-4 did not augment the MLR activity of these cells. AML cells cultured with CI in the presence or absence of IL-4 showed increased levels of apoptosis in comparison to primary cultures of AML cells.

Conclusion

Although CI appears to be advantageous in terms of time and cost effectiveness, the results of the present study suggest that the marked induction of apoptosis by CI limits its application to the generation of DCs from AML cells.

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The plasticity and potential of leukemia cell lines to differentiate into dendritic cells
QINGWEI GUO, LELING ZHANG, FU LI, GUOSHENG JIANG
Oncology Letters.2012; 4(4): 595. CrossRef

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The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony-Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia: Young Joo Min, Cheol Won Suh, Keon Uk Park, Sung Soo Yoon, Chan Hyung Park, Hong Ghi Lee; Cancer Res Treat. 2003;35(1):66-68. Published online February 28, 2003; DOI: https://doi.org/10.4143/crt.2003.35.1.66

Abstract PDF: PURPOSE
This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo-skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML.

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Prognostic Implications of Cytarabine Dose in Consolidation Chemotherapy for the Patients with Acute Myelogenous Leukemia: Jung Hee Lee, Je Hwan Lee, Kyoo Hyung Lee, Hyeseung Bahng, Jin Hee Ahn, Jung Shin Lee, Sang Hee Kim, Woo Kun Kim; J Korean Cancer Assoc. 2000;32(5):954-961.

Abstract PDF: PURPOSE
Increasing the dose of cytarabine in consolidation chemotherapy has been suggested to improve treatment outcome of the patients with acute myelogenous leukemia (AML) in complete remission (CR). We studied an effect of cytarabine dose in consolidation chemotherapy on the survival times.
MATERIALS AND METHODS
From 1989 to 1998, AML patients in CR who received two or more courses of consolidation chemotherapy were included. At the first course of consolidation chemo therapy, all patients received standard dose of cytarabine (100 or 200 mg/m2/day by a continuous infusion for 5 days) plus anthracyclines. At the second or third course, one of three dose levels of cytarabine was given with anthracyclines. Three dose levels of cytarabine were standard dose (SD), intermediate dose (ID, 1 or 2 g/m2/day by a 3-hour infusion for 5 days), and high dose (HD, 3 g/m2 in a 3-hour infusion every 12 hours for total six doses). We retrospectively reviewed clinical records of study patients.
RESULTS
64 patients were included. The median follow-up duration of alive patients was 1,143 days. Estimated 3-year overall survival times were 24% in SD group, 41% in ID group and 56% in HD group (P=0.737). Estimated 3-year disease free survival times were 18%, 16% and 44% in each group (P=0.592). There was no significant difference in toxicity of consolidation chemotherapy between three groups.
CONCLUSION
Although the survival times showed a trend to be longer in the patients who received higher dose of cytarabine as consolidation chemotherapy, there were no statistically significant differences.

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A Clinical Study of Pediatric Myelodysplastic Syndrome: Application of International Prognostic Scoring System and the Review of the Korean Literature: Hoon Kook, Chan Jong Kim, Weon Sang Yoon, Na Eun Ryu, Kyoung Joong Chung, Tai Ju Hwang; J Korean Cancer Assoc. 2000;32(1):178-190.

Abstract PDF: PURPOSE
Myelodysplastic syndrome (MDS) in children needs to be elucidated in terms of clinical characteristics, natural history, the most effective treatment and prognostic factors, as the disease is very rare and its definition and classification has not reached a consensus by many physician. This study was aimed to describe the characteristics and the disease courses of Korean children with MDS, and to analyze the usefulness of prognostic scoring systems in the prediction of transformation to acute myelogenous leukemia (AML) and overall survival among subgroups.
MATERIALS AND METHODS
Fourteen children with MDS seen at Chonnam University Hospital and additional 59 patients identified by the review of Korean literature were evaluated to define clinical characteristics and disease courses. Kaplan-Meier (K-M) probability of leukemic transformation and overall survival were plotted. FAB subtypes, subgroups by Boumemouth Scoring System (BSS), and International Prognostic Scoring System (IPSS) risk groups were compared to predict transformation to AML and overall survival.
RESULTS
The median age of 14 patients was 36.5 months. The sex ratio was 3.7:1 (M: F). The frequency of FAB subtypes in Korea was similar to that of other countries except for higher proportion of RA (37%). K-M 3-yr probability of AML transformation and survival for Korean patients were 54.7%, and 49.8%, respectively. Although FAB system, BMS and IPSS were all capable of discriminating subgroups in the prediction of AML transformation and survival, they did not reach the significant level possibly due to small number of patients assigned to each subgroup.
CONCLUSION
The clinical characteristics of Korean children with MDS were not different from those of other countries. This study showed the high rate of AML transformation and poor survival in children with MDS.

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