Cancer Research and Treatment

Original Articles

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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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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Prognostic value of CEBPA bZIP signatures in cytogenetically normal acute myeloid leukaemia
Li‐Xin Wu, Ming‐Yue Liao, Ming‐Yue Zhao, Nan Yan, Ping Zhang, Li‐Xia Liu, Jia‐Yue Qin, Shan‐Bo Cao, Jia Feng, Qian Jiang, Ying‐Jun Chang, Lan‐Ping Xu, Xiao‐Hui Zhang, Xiao‐Jun Huang, Hao Jiang, Hong‐Yu Zhang, Guo‐Rui Ruan
British Journal of Haematology.2025;[Epub] CrossRef
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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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

Abstract PDF PubReader ePub

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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Sabine Kayser, Shannon E. Conneely
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Chi-kong Li, Purna Kurkure, Ramandeep Singh Arora, Bow Wen Chen, Kirill Kirgizov, Yasuhiro Okamoto, Panya Seksarn, Yongmin Tang, Keon Hee Yoo, Bharat Agarwal, Godfrey C.F. Chan, Rashmi Dalvi, Hiroki Hori, Muhammad Saghir Khan, Alice Yu, Akira Nakagawara
JCO Global Oncology.2023;[Epub] CrossRef
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Anna Maria Testi, Mazin Faisal Al-Jadiry, Hasanein Habeeb Ghali, Samaher Abdulrazzaq Fadhil, Amir Fadhil Al-Darraji, Raghad Majid Al-Saeed, Ahmed Hatem Sabhan, Safaa A. Faraj Al-Badri, Wisan Majeed Abed, Najiha Ahmed Ameen, Ruaa Zaki Al-Tameemi, Arabiya I
Leukemia & Lymphoma.2022; 63(12): 2940. CrossRef
Death due to unsuspected acute myeloid leukaemia: an unusual forensic diagnosis
Lila Krebs-Drouot, Georgia Karpathiou, Virginie Scolan, Carolyne Bidat-Callet, Baptiste Boyer, Michel Péoc’h
Forensic Science, Medicine and Pathology.2022; 19(1): 60. CrossRef
Successful Treatment of Isolated Central Nervous System Relapse with Intrathecal Chemotherapy in an Adolescent with Acute Promyelocytic Leukemia
Haerim Song, Eun Sang Yi
Clinical Pediatric Hematology-Oncology.2022; 29(2): 70. CrossRef

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Lung Cancer

Clinical Significance of Acute Kidney Injury in Lung Cancer Patients: Semin Cho, Eunjeong Kang, Ji Eun Kim, U Kang, Hee Gyung Kang, Minsu Park, Kwangsoo Kim, Dong Ki Kim, Kwon Wook Joo, Yon Su Kim, Hyung-Jin Yoon, Hajeong Lee; Cancer Res Treat. 2021;53(4):1015-1023. Published online January 18, 2021; DOI: https://doi.org/10.4143/crt.2020.1010

Abstract PDF Supplementary Material PubReader ePub

Purpose
Acute kidney injury (AKI) in cancer patients is associated with increased morbidity and mortality. The incidence of AKI in lung cancer seems to be relatively higher compared with other solid organ malignancies, although its impact on patient outcomes remains unclear.
Materials and Methods
The patients newly diagnosed with lung cancer from 2004 to 2013 were enrolled in this retrospective cohort study. The patients were categorized according to the presence and severity of AKI. We compared all-cause mortality and long-term renal outcome according to AKI stage.
Results
A total of 3,202 patients were included in the final analysis. AKI occurred in 1,783 (55.7%) patients during the follow-up period, with the majority having mild AKI stage 1 (75.8%). During the follow-up of 2.6±2.2 years, total 1,251 patients (53.7%) were died and 5-year survival rate was 46.9%. We found that both AKI development and severity were independent risk factors for all-cause mortality in lung cancer patients, even after adjustment for lung cancer-specific variables including the stage or pathological type. In addition, patients suffered from more severe AKI tend to encounter de novo chronic kidney disease development, worsening kidney function, and end-stage kidney disease progression.
Conclusion
In this study, more than half of the lung cancer patients experienced AKI during their diagnosis and treatment period. Moreover, AKI occurrence and more advanced AKI were associated with a higher mortality risk and adverse kidney outcomes.

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Acute kidney injury associated with anti-PD-1 and anti-PD-L1 drugs: a meta-analysis of randomized clinical trials
Isabela Gonçalves Lima, Isabele Benck Usiro Cabral da Silva, Vitória Carpentieri Pípolo, Vinicius Daher Alvares Delfino, Paulo Roberto Bignardi
Immunopharmacology and Immunotoxicology.2024; 46(4): 470. CrossRef
Prevalence of kidney disease in patients with different types of cancer or hematological malignancies: a cross-sectional study
Feng Wu, Shiyuan Wang, Jialing Zhang, Peixin Wang, Aihua Zhang
International Urology and Nephrology.2024; 56(12): 3835. CrossRef
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Ying Huang, Yang Li, Xialian Xu, Jie Teng, Xiaoqiang Ding, Jiarui Xu
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Huijuan Qian, Si Li, Ziyun Hu
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Xiayuan Huang, ShuShun Ren, Xinyue Mao, Serena Chen, Elle Chen, Yuqi He, Yun Jiang
JMIR Cancer.2024;[Epub] CrossRef
Association and prediction of red blood cell distribution width to albumin ratio in all-cause mortality of acute kidney injury in critically ill patients
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Point of care ultrasonography in onco-nephrology: A stride toward better physical examination
Bhavna Bhasin-Chhabra, Abhilash Koratala
World Journal of Nephrology.2023; 12(2): 29. CrossRef
Protocolo diagnóstico y tratamiento de la nefropatía en los pacientes con neoplasia sólida
Rodríguez Doyágüez, M.P. Morán Magro, C.M. Durán López, P. Martínez Miguel
Medicine - Programa de Formación Médica Continuada Acreditado.2023; 13(82): 4870. CrossRef

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Pediatric cancer

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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Swathi Putta, Santhosh Kumar Chinnaiyan, Ramadevi Korni, Venkata Radha Gadela
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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
RSC Chemical Biology.2025; 6(6): 845. CrossRef
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Christian Omar Ramos-Peñafiel, Carlos Martínez-Murillo, Daniela Pérez-Sámano, Camila Terreros-Palacios, Adán Germán Gallardo-Rodríguez, Irma Olarte-Carrillo, Adolfo Martínez-Tovar
Revista Médicas UIS.2024;[Epub] CrossRef
Clofarabine

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Patient-Level Meta-analysis of Clofarabine in Acute Lymphoblastic Leukemia
Sima Jeha, Hiroaki Goto, André Baruchel, Emmanuelle Boëlle-Le Corfec, Christine Geffriaud-Ricouard, Rob Pieters, Hee Young Shin
Advances in Therapy.2023; 40(12): 5447. CrossRef
Novel Treatments for Pediatric Relapsed or Refractory Acute B-Cell Lineage Lymphoblastic Leukemia: Precision Medicine Era
Shang Mengxuan, Zhou Fen, Jin Runming
Frontiers in Pediatrics.2022;[Epub] CrossRef

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Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy: Jie Yang, Ying Huang, Yanru Feng, Hongmin Li, Ting Feng, Jinna Chen, Luxi Yin, Weihu Wang, Shulian Wang, Yueping Liu, Yongwen Song, Yexiong Li, Jing Jin, Wen Tan, Dongxin Lin; Cancer Res Treat. 2019;51(3):1198-1206. Published online December 26, 2018; DOI: https://doi.org/10.4143/crt.2018.527

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT).
Materials and Methods
Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model.
Results
The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer.
Conclusion
These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.

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Xiaoyi Hu, Shang Wang, Hui Zhao, Yaqin Wei, Ruowang Duan, Rong Jiang, Wenhui Wu, Qinhua Zhao, Sugang Gong, Lan Wang, Jinming Liu, Ping Yuan
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Vivian Salama, Yimin Geng, Jillian Rigert, Clifton D. Fuller, Sanjay Shete, Amy C. Moreno
Clinical and Translational Radiation Oncology.2023; 43: 100669. CrossRef
Tumor-infiltrating lymphocytes, PD-L1, and MMR-deficiency combined characterization may identify subgroups of rectal cancer patients who would benefit from immunotherapy
Alexandra Giatromanolaki, Christos Kavazis, Anastasia G. Gkegka, Maria Kouroupi, Alexandra Tsaroucha, Michael Pitiakoudis, Michael I. Koukourakis
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SYVN1‐mediated ubiquitination and degradation of MSH3 promotes the apoptosis of lens epithelial cells
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Dietary methyl donor nutrients, DNA mismatch repair polymorphisms, and risk of colorectal cancer based on microsatellite instability status
Jimi Kim, Jeonghee Lee, Jae Hwan Oh, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim, Hee Jin Chang
European Journal of Nutrition.2022; 61(6): 3051. CrossRef
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Long-term Outcomes of One Stage Surgery Using Transanal Colorectal Tube for Acute Colorectal Obstruction of Stage II/III Distal Colon Cancer: Yusuke Okuda, Tomonori Yamada, Yoshikazu Hirata, Takaya Shimura, Ryuzo Yamaguchi, Eiji Sakamoto, Satoshi Sobue, Takahiro Nakazawa, Hiromi Kataoka, Takashi Joh; Cancer Res Treat. 2019;51(2):474-482. Published online June 6, 2018; DOI: https://doi.org/10.4143/crt.2018.059

Abstract PDF PubReader ePub

Purpose
Since oncological outcomes of transanal colorectal tube (TCT) placement, an endoscopic treatment for colorectal cancer (CRC) with acute colorectal obstruction (ACO), remain unknown, this study analyzed long-term outcomes of TCT placement for stage II/III CRC with ACO.
Materials and Methods
Data were retrospectively reviewed from consecutive patients with distal stage II/III CRC who underwent surgery between January 2007 and December 2011 at two Japanese hospitals. One hospital conducted emergency surgery and the other performed TCT placement as the standard treatment for all CRCs with ACO. Propensity score (PS) matching was used to adjust baseline characteristics between two groups.
Results
Among 754 patients with distal stage II/III CRC, 680 did not have ACO (non-ACO group) and 74 had ACO (ACO group). The PS matching between both hospitals identified 234 pairs in the non-ACO group and 23 pairs in the ACO group. In the non-ACO group, the surgical quality was equivalent between the two institutions, with no significant differences in overall survival (OS) and disease-free survival (DFS). In the ACO group, the rate of primary resection/anastomosis was higher in the TCT group than in the surgery group (87.0% vs. 26.1%, p < 0.001). No significant differences were noted between the surgery and the TCT groups in OS (5-year OS, 61.9% vs. 51.5%; p=0.490) and DFS (5-year DFS, 45.9% vs. 38.3%; p=0.658).
Conclusion
TCT placement can achieve similar long-term outcomes to emergency surgery, with a high rate of primary resection/anastomosis for distal stage II/III colon cancer with ACO.

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Comparison of the prognosis of four different treatment strategies for acute left malignant colonic obstruction: a systematic review and network meta-analysis
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Jian Lv, Yuan yuan Liu, Yi tao Jia, Jing li He, Guang yao Dai, Peng Guo, Zhao long Zhao, Yan ni Zhang, Zhong xin Li
World Journal of Surgical Oncology.2021;[Epub] CrossRef
The long non‐coding RNA HCG18 promotes the growth and invasion of colorectal cancer cells through sponging miR‐1271 and upregulating MTDH/Wnt/β‐catenin
Shunle Li, Tao Wu, Di Zhang, Xiaoli Sun, Xinwu Zhang
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Li Ren, Zhiyong Zhang, Yun Feng, Miaosha Luo, Zhiming Hao
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Pathological impact of transanal colorectal tube for obstructive colorectal cancer
Yusuke Okuda, Takaya Shimura, Hiroyuki Kato, Tomonori Yamada, Yoshikazu Hirata, Makoto Natsume, Hiroyasu Iwasaki, Ryuzo Yamaguchi, Eiji Sakamoto, Satoru Takahashi, Hiromi Kataoka
Surgical Endoscopy.2020; 34(9): 4011. 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
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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
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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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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
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Gene regulations and delivery vectors for treatment of cancer
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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
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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
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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
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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

Coexistence of VHL Disease and CPT2 Deficiency: A Case Report: Alfonso Massimiliano Ferrara, Monica Sciacco, Stefania Zovato, Silvia Rizzati, Irene Colombo, Francesca Boaretto, Maurizio Moggio, Giuseppe Opocher; Cancer Res Treat. 2016;48(4):1438-1442. Published online March 25, 2016; DOI: https://doi.org/10.4143/crt.2015.450

Abstract PDF PubReader ePub

von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2) is a disorder of lipid metabolism that, in the muscle form, manifests with recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic episodes may be complicated by life-threatening events, including acute renal failure (ARF). We report on a male patient who was tested, at 10 years of age, for VHL disease because of family history of VHL. He was diagnosed with VHL but without VHL-related manifestation at the time of diagnosis. During childhood, the patient was hospitalized several times for diffuse muscular pain, muscle weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never accompanied by ARF. The patient was found to be homozygous for the mutation p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations.

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Genotype–phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions
Kenan Zhang, Wuping Yang, Kaifang Ma, Jianhui Qiu, Lei Li, Yawei Xu, Zedan Zhang, Chaojian Yu, Jingcheng Zhou, Yanqing Gong, Lin Cai, Kan Gong
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Jingyu Wang, Yi Liu, Yaqing Wang, Li Sun, Ana Cipak Gasparovic
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Animal Genetics.2019; 50(6): 726. CrossRef

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Original Article

Frequency and Outcome of Neuroleptic Rotation in the Management of Delirium in Patients with Advanced Cancer: Seong Hoon Shin, David Hui, Gary Chisholm, Jung Hun Kang, Julio Allo, Janet Williams, Eduardo Bruera; Cancer Res Treat. 2015;47(3):399-405. Published online November 24, 2014; DOI: https://doi.org/10.4143/crt.2013.229

Abstract PDF PubReader ePub

Purpose
The response to haloperidol as a first-line neuroleptic and the pattern of neuroleptic rotation after haloperidol failure have not been well defined in palliative care. The purpose of this study was to determine the efficacy of haloperidol as a first-line neuroleptic and the predictors associated with the need to rotate to a second neuroleptic. Materials and Methods We conducted a retrospective review of the charts of advanced cancer patients admitted to our acute palliative care unit between January 2012 and March 2013. Inclusion criteria were a diagnosis of delirium and first-line treatment with haloperidol. Results Among 167 patients with delirium, 128 (77%) received only haloperidol and 39 (23%) received a second neuroleptic. Ninety-one patients (71%) who received haloperidol alone improved and were discharged alive. The median initial haloperidol dose was 5 mg (interquartile ranges [IQR], 3 to 7 mg) and the median duration was 5 days (IQR, 3 to 7 days). The median final haloperidol dose was 6 mg (IQR, 5 to 7 mg). A lack of treatment efficacy was the most common reason for neuroleptic rotation (87%). Significant factors associated with neuroleptic rotation were inpatient mortality (59% vs. 29%, p=0.001), and being Caucasian (87% vs. 62%, p=0.014). Chlorpromazine was administered to 37 patients (95%) who were not treated successfully by haloperidol. The median initial chlorpromazine dose was 150 mg (IQR, 100 to 150 mg) and the median duration was 3 days (IQR, 2 to 6 days). Thirteen patients (33%) showed reduced symptoms after the second neuroleptic. Conclusion Neuroleptic rotation from haloperidol was only required in 23% of patients with delirium and was associated with inpatient mortality and white race.

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Kavita Algu, Joshua Wales, Michael Anderson, Mariam Omilabu, Thandi Briggs, Allison M. Kurahashi
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Ahsan Azhar, David Hui
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A Scoping Review to Map Empirical Evidence Regarding Key Domains and Questions in the Clinical Pathway of Delirium in Palliative Care
Peter G. Lawlor, Nicole A. Rutkowski, Alistair R. MacDonald, Mohammed T. Ansari, Lindsey Sikora, Franco Momoli, Salmaan Kanji, David K. Wright, Erin Rosenberg, Annmarie Hosie, Jose L. Pereira, David Meagher, Jill Rice, John Scott, Shirley H. Bush
Journal of Pain and Symptom Management.2019; 57(3): 661. CrossRef
Prevalencia de delirium mediante la escala Memorial Delirium Assessment Scale (MDAS) en pacientes oncológicos avanzados ingresados en una Unidad de Cuidados Paliativos. Factores de riesgo, reversibilidad y tratamiento recibido
Verónica Díaz García, Miriam López Pérez, Yolanda Zuriarrain Reyna
Medicina Paliativa.2018; 25(4): 245. CrossRef
Clinical Assessment and Management of Delirium in the Palliative Care Setting
Shirley Harvey Bush, Sallyanne Tierney, Peter Gerard Lawlor
Drugs.2017; 77(15): 1623. CrossRef
Delirium Management: Diagnosis, Assessment, and Treatment in Palliative Care
Min Seok Seo, Yong Joo Lee
The Korean Journal of Hospice and Palliative Care.2016; 19(3): 201. CrossRef
Neuroleptics in the management of delirium in patients with advanced cancer
David Hui, Rony Dev, Eduardo Bruera
Current Opinion in Supportive & Palliative Care.2016; 10(4): 316. CrossRef
Acute symptomatic complications among patients with advanced cancer admitted to acute palliative care units: A prospective observational study
David Hui, Renata dos Santos, Suresh Reddy, Maria Salete de Angelis Nascimento, Donna S Zhukovsky, Carlos Eduardo Paiva, Shalini Dalal, Everaldo Donizeti Costa, Paul Walker, Heloisa Helena Scapulatempo, Rony Dev, Camila Souza Crovador, Maxine De La Cruz,
Palliative Medicine.2015; 29(9): 826. CrossRef

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Case Report

Tumor Lysis Syndrome in a Solid Tumor: A Case Report of a Patient with Invasive Thymoma: Ji Yun Lee, Sung Hee Lim, Ji Young Lee, Ji Hoon Kim, Ki Hong Choi, Keunchil Park, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn; Cancer Res Treat. 2013;45(4):343-348. Published online December 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.4.343

Abstract PDF PubReader ePub

Tumor lysis syndrome (TLS) has rarely been observed in solid tumors. We report on a case of a patient with advanced invasive thymoma who developed tumor lysis syndrome after chemotherapy. The potential complications of TLS should be considered in treatment of extensive thymoma.

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Spontaneous tumour lysis syndrome as a rare presentation of thymoma with peripheral blood lymphocytosis
Larry E Nyanti, Andy Sing Ong Tang, Adam Malik b Ismail, Lee Ping Chew, Tze Shin Leong
Proceedings of Singapore Healthcare.2022;[Epub] CrossRef
Tumor Lysis Syndrome in Patients With Solid Tumors: A Systematic Review of Reported Cases
Riyadh M Alqurashi , Husam H Tamim, Ziyad D Alsubhi, Alyazid A Alzahrani, Emad Tashkandi
Cureus.2022;[Epub] CrossRef
Spontaneous tumour lysis syndrome in cervical cancer
Yu Kyung Kim, Ji Yeon Ham, Won-Kil Lee, Kyung Eun Song
Journal of Obstetrics and Gynaecology.2017; 37(5): 679. CrossRef
Ifosfamide/mesna/paclitaxel

Reactions Weekly.2015; 1547(1): 151. CrossRef
Tumor Lysis Syndrome in Solid Tumors: An up to Date Review of the Literature
Aibek E. Mirrakhimov, Alaa M. Ali, Maliha Khan, Aram Barbaryan
Rare Tumors.2014; 6(2): 68. CrossRef

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4 Web of Science
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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

Abstract PDF PubReader ePub

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

Abstract PDF PubReader ePub

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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Original Articles

Treatment Outcome of Cisplatin-based Concurrent Chemoradiotherapy in the Patients with Locally Advanced Nasopharyngeal Cancer: Tae Hee Kim, Yoon Ho Ko, Myung Ah Lee, Bum-soo Kim, So Ryoung Chung, Ie Ryung Yoo, Chan-Kwon Jung, Yeon-Sil Kim, Min Sik Kim, Dong-Il Sun, Young Seon Hong, Kyung Shik Lee, Jin-Hyoung Kang; Cancer Res Treat. 2008;40(2):62-70. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.62

Abstract PDF PubReader ePub

Purpose

The standard treatment of locally advanced nasopharyngeal cancer is a concurrent chemoradiotherapy (CCRT), and cisplatin has been used as the most popular chemotherapeutic agent. But many different doses and schedules for cisplatin administration such as daily, weekly and 3 week cycles have been proposed. We compared and analyzed the tumor response, the overall survival, the toxicity and the chemotherapy dose intensity in the patients with locally advanced nasopharyngeal cancer who were treated with CCRT.

Materials and Methods

We performed a retrospective study on 55 patients with locally advanced nasopharyngeal cancer, and they were treated with CCRT as a front-line treatment from Jan 1996 to Jun 2007 at Kangnam Saint Mary's Hospital.

Results

The patients had a median age of 53 years (range: 19~75 years). Of the total 55 patients, a 3-week cycle of 100mg cisplatin was administered in 31 patients and 30 mg weekly cisplatin was administered in 24 patients combined with radiotherapy. Twenty one patients had a complete response and four patients had a partial response for a response rate of 71.4% (95% CI: 59.5~83.3) after CCRT and followed by adjuvant chemotherapy. The complete response rates for the 30 mg and 100 mg cisplatin groups were 72.7% (95% CI: 54.9~90.5) and 54.2% (95% CI: 36.7~71.7), respectively (p=0.23). The duration of CCRT in the 100mg cisplatin group was significantly longer than that of the 30mg cisplatin group (11.1±2.9 weeks vs. 9.0±1.2 weeks, p=0.003). The major deviation group, which was defined as prolongation of the radiotherapy duration for more than 2 weeks, had a significantly lower objective response rate than did the non-deviation group (56.3% vs 84.2%, respectively, p=0.002). The major severe toxicities were leucopenia (49.1%), pharyngoesophagitis (49.1%), anorexia (43.6%), nausea (41.8%) and vomiting (40%).

Conclusions

Weekly 30mg cisplatin-based CCRT is a practical, feasible cisplatin schedule for the patients with locally advanced nasopharyngeal cancer in regard to decreasing the interruption of radiation treatment and decreasing the treatment-related acute toxicities.

Citations

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A prognostic and predictive model based on deep learning to identify optimal candidates for intensity-modulated radiotherapy alone in patients with stage II nasopharyngeal carcinoma: A retrospective multicenter study
Jiong-Lin Liang, Yue-Feng Wen, Ying-Ping Huang, Jia Guo, Yun He, Hong-Wei Xing, Ling Guo, Hai-Qiang Mai, Qi Yang
Radiotherapy and Oncology.2025; 203: 110660. CrossRef
The Effect of Prolonged Duration of Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma
Yi-Jun Hua, Yan-Feng Ou-Yang, Xiong Zou, Le Xia, Dong-Hua Luo, Ming-Yuan Chen
Frontiers in Oncology.2021;[Epub] CrossRef
Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort
S. Ghosh-Laskar, A. Pilar, K. Prabhash, A. Joshi, J.P. Agarwal, T. Gupta, A. Budrukkar, V. Murthy, M. Swain, V. Noronha, V.M. Patil, P. Pai, D. Nair, D.A. Chaukar, S. Thiagarajan, G. Pantvaidya, A. Deshmukh, P. Chaturvedi, S. Nair, A. D‘Cruz
Clinical Oncology.2019; 31(12): 850. CrossRef
Long-term outcomes of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma treated with IMRT: a retrospective study
Zhen Su, Yan-Ping Mao, Jie Tang, Xiao-Wen Lan, Pu-Yun OuYang, Fang-Yun Xie
Tumor Biology.2016; 37(4): 4429. CrossRef
Concurrent chemoradiotherapy was associated with a higher severe late toxicity rate in nasopharyngeal carcinoma patients compared with radiotherapy alone: a meta-analysis based on randomized controlled trials
Cheng-run Du, Hong-mei Ying, Fang-fang Kong, Rui-ping Zhai, Chao-su Hu
Radiation Oncology.2015;[Epub] CrossRef
Concurrent Chemotherapy for T4 Classification Nasopharyngeal Carcinoma in the Era of Intensity-Modulated Radiotherapy
Cai-neng Cao, Jing-wei Luo, Li Gao, Jun-lin Yi, Xiao-dong Huang, Kai Wang, Shi-ping Zhang, Yuan Qu, Su-yan Li, Jian-ping Xiao, Zhong Zhang, Guo-zhen Xu, Riccardo Dolcetti
PLOS ONE.2015; 10(3): e0119101. CrossRef
Controversies in the systemic treatment of Nasopharyngeal carcinoma
Herbert H. Loong, Anthony T.C. Chan
Oral Oncology.2014; 50(9): 785. CrossRef
Intensity-modulated radiotherapy with simultaneous integrated boost for locoregionally advanced nasopharyngeal carcinoma
Junlin Yi, Xiaodong Huang, Li Gao, Jingwei Luo, Shiping Zhang, Kai Wang, Yuan Qu, Jianping Xiao, Guozhen Xu
Radiation Oncology.2014;[Epub] CrossRef
Factors Predict Prolonged Wait Time and Longer Duration of Radiotherapy in Patients with Nasopharyngeal Carcinoma: A Multilevel Analysis
Po-Chun Chen, Ching-Chieh Yang, Cheng-Jung Wu, Wen-Shan Liu, Wei-Lun Huang, Ching-Chih Lee, Bart O. Williams
PLoS ONE.2014; 9(10): e109930. CrossRef
Pretreatment Epstein-Barr Virus DNA Load and Cumulative Cisplatin Dose Intensity Affect Long-Term Outcome of Nasopharyngeal Carcinoma Treated with Concurrent Chemotherapy: Experience of an Institute in an Endemic Area
Weihong Wei, Zeli Huang, Shaoen Li, Hemei Chen, Guoyi Zhang, Shuxia Li, Weihan Hu, Tao Xu
Oncology Research and Treatment.2014; 37(3): 88. CrossRef
Concurrent Chemoradiotherapy vs Radiotherapy Alone in Stage II Nasopharyngeal Carcinoma: Phase III Randomized Trial
Qiu-Yan Chen, Yue-Feng Wen, Ling Guo, Huai Liu, Pei-Yu Huang, Hao-Yuan Mo, Ning-Wei Li, Yan-Qun Xiang, Dong-Hua Luo, Fang Qiu, Rui Sun, Man-Quan Deng, Ming-Yuan Chen, Yi-Jun Hua, Xiang Guo, Ka-Jia Cao, Ming-Huang Hong, Chao-Nan Qian, Hai-Qiang Mai
JNCI: Journal of the National Cancer Institute.2011; 103(23): 1761. CrossRef
Radiation Therapy Combined with (or without) Cisplatin-based Chemotherapy for Patients with Nasopharyngeal Cancer: 15-years Experience of a Single Institution in Korea
Yeon-Sil Kim, Bum-Soo Kim, So-Lyoung Jung, Yeon-Soo Lee, Min-Sik Kim, Dong-Il Sun, Eun-Jung Yoo, Seong-Kwon Mun, Sei-Chul Yoon, Su-Mi Chung, Hoon-Kyo Kim, Seung-Ho Jo, Jin-Hyoung Kang
Cancer Research and Treatment.2008; 40(4): 155. CrossRef

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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

Abstract PDF PubReader ePub

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.

Citations

Citations to this article as recorded by

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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Case Report

Carboxypeptidase-G2 Rescue in a Patient with High Dose Methotrexate-induced Nephrotoxicity: Eun Sil Park, Kyung Hee Han, Hyoung Soo Choi, Hee Young Shin, Hyo Seop Ahn; Cancer Res Treat. 2005;37(2):133-135. Published online April 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.2.133

Abstract PDF PubReader ePub

A 13 year-old girl with osteosarcoma and pulmonary tumor recurrence developed acute renal failure following high dose methotrexate (12 g/m²) therapy, she had previously tolerated high dose methotrexate and her renal and hepatic functions were normal. Briefly, 48 hours after beginning methotrexate infusion her methotrexate concentration and creatinine level were 1338.8 µM/L and 5.8 mg/dl, respectively. Grade IV oral mucositis and neutropenia with fever developed at 144 hours after MTX infusion. Hydration and alkalinization were continued and leucovorin rescue was intensified based on the plasma MTX concentrations. Plasma exchange was performed twice and hemodialysis 3 times without problems, but methotraxate and creatinine levels remained high, 91.9 µM/L, and 2.5 mg/dl, respectively. After 3 courses of hemodialysis carboxypeptidase-G2 (CPDG2) was administered at 50 U/kg, intravenously over 5 minutes. After 15 minutes of CPDG2 (Voraxaze™) infusion, her plasma MTX concentration was 0.91 µM/L and no rebound elevation or side effects developed. Thirteen days post-MTX infusion her renal function had normalized. We report here our experience of a dramatic methotrexate level reduction caused by CPDG2 administration.

Citations

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Extracorporeal Treatment for Methotrexate Poisoning
Marc Ghannoum, Darren M. Roberts, David S. Goldfarb, Jesper Heldrup, Kurt Anseeuw, Tais F. Galvao, Thomas D. Nolin, Robert S. Hoffman, Valery Lavergne, Paul Meyers, Sophie Gosselin, Tudor Botnaru, Karine Mardini, David M. Wood
Clinical Journal of the American Society of Nephrology.2022; 17(4): 602. CrossRef
Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients
Jeffrey R. Scott, Yinmei Zhou, Cheng Cheng, Deborah A. Ward, Hope D. Swanson, Alejandro R. Molinelli, Clinton F. Stewart, Fariba Navid, Sima Jeha, Mary V. Relling, Kristine R. Crews
Pediatric Blood & Cancer.2015; 62(9): 1518. CrossRef
Resumption of high‐dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients
Anthony M. Christensen, Jennifer L. Pauley, Alejandro R. Molinelli, John C. Panetta, Deborah A. Ward, Clinton F. Stewart, James M. Hoffman, Scott C. Howard, Ching‐Hon Pui, Alberto S. Pappo, Mary V. Relling, Kristine R. Crews
Cancer.2012; 118(17): 4321. CrossRef

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Original Articles

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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Autologous or Allogeneic Bone Marrow Transplantation Compared with Consolidation Chemotherapy in Acute promyelocytic Leukemia: Chang Ki Min, Woo Sung Min, Hee Je Kim, Hyun Suk Eom, Jong Wook Lee, Kyungja Han, Ihl Bhong Choi, Chun Choo Kim, Won IL Kim, Dong Jip Kim; J Korean Cancer Assoc. 1999;31(2):331-338.

Abstract PDF: PURPOSE
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia characterized by the morphology of blast cells (M3 in FAB classification), the t (15;17) translocation, and a coagulopathy combining disseminated intravascular coagulation and fibrinolysis. It has been considered to have better response to combination chemo- therapy of an anthracycline and cytosine arabinoside and a higher cure rate than other subtypes because of recent approach of differentiating leukemic blasts by all-transretinoic acid (ATRA). The role of stem cell transplantation in APL has to be determined in comparison with that of consolidation chemotherapy.
MATERIALS AND METHODS
We compared the leukemia-free survival and overall survival between APL patients receiving the consolidation chemotherapy and those undergoing the allogeneic or autologous stem cell transplantation following the high-dose anticancer therapy. Of the 65 patients achieving the first complete remission from 1992 to 1997, 33 patients were treated with 3 courses of consolidation chemotherapies and 32 with the stem cell transplantation.
RESULTS
With a median follow-up of 22 months (8-60), the actuarial leukemia-free survival at 3 years was significantly higher in transplantation group than in chematherapy group (73.8% versus 33.5%; P=0.0087), and the probability of leukemic relapse was considerably lower in transplantation group than in chemotherapy group (6.3% versus 57.5%; P=0.001). The treatment-related mortalities of the groups were 0% in chemotherapy group and 14.3% in transplantation group. The main cause of deaths was relapse in the consolidation chemotherapy group.
CONCLUSION
These data demonstrate that the stem cell transplantation results in better leukemia-free survival than the consolidation chemotherapy for patients with APL in the first complete remission because of lower risk of relapse.

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Expression of Multidrug Resistant Genes in Bone Marrow Mononuclear Cells of Patients with Myeloid Leukemia: Seok Goo Cho, Il Ho Yang, Hyeon Seok Eom, Chang Gi Min, Hee Je Kim, Dong Wook Kim, Jong Wook Lee, Chi Wha Han, Woo Sung Min, Won Il Kim, Chun Choo Kim; J Korean Cancer Assoc. 1999;31(1):153-164.

Abstract PDF: PURPOSE
Multidrug resistance mediated by several drug resistant genes impedes the successful outcome of anti-cancer chemotherapy. In this study, we investigated the expressions of drug resistant genes encoding multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), topoisomerase I (Topo I), topoisomerase II g (Topo II a) in narmal volunteers (n=12) in and patients with myeloid leukemia (n=34). Material and Method: We compared the levels of their transcripts in bone matrow mononuclear cells by semiquantitative RT-PCR. The amount of specific transcripts was represented as the optical density ratio of PCR product of target gene to that of B2- microglobulin (MG). Twenty patients of acute myelogenous leukemia (eight in remission state, twelve in refractory) and fourteen patients of chronic myelogenous leukemia (nine in chronic phase and five in blastic crisis) were examined. Twelve normal healthy persons were compared with leukemic patients.
RESULTS
The expression levels of all resistant genes in normal volunteers were relatively high as those of AML patients. Regardless of the disease status including remission status of AML (complete remission versus refractory) and the phase of CML (chronic phase versus blastic phase), the expression levels of all resistant genes in patients with CML were significantly lower than in the patients with AML (p < 0.05). Of interest, the patients with refractary AML did not show any statistical difference in comparison with normal controls and even the patients with AML in complete remission. Among the four drug resistant genes, the optical density ratio of MDRl was significantly lower than that of any other genes (p<0.05). Using HL-60 cell line, we compared the changes of various resistant gene expressions before and after differentiation induced by dimethylsulfoxide. The expressions of resistant genes declined in paralle1 with granulocytic differentiation, suggesting that the induction of cell differentiation might make leukemic cells susceptible to chemotherapeutic agents.
CONCLUSION
It is impossibble to explain the mechanism of drug resistance by comparing the level of drug resistant gene expression between nonnal subjects and patients with myeloid leukemias. Therefore, we suppose that longitudinal study of drug resistant gene expression is necessary to demonstrate the development of drug resistant during chemotherapy.

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Clinical Trial

The Effect of Cytosine Arabinoside and Daunorubicin(AD) Combination Chemotherapy in Acute Myelogeous Leukemia: Chang Hoon Moon, Sung Hyun Kim, Hyung Ryoul Park, Jung Hwan Cho, Hyok Chan Kwon, Jae Seok Kim, Hyo Jin Kim; J Korean Cancer Assoc. 1998;30(4):842-852.

Abstract PDF: PURPOSE
Important advances in the treatment of acute myelogenous leukemia have been made with the introduction of cytosine arabinoside(ara-C) and anthracycline(daunorubicin) over the past 20 years. Currently, 50 to 85% of patients with acute myelogenous leukemia achieve complete remission with induction chemotherapy consisting of ara-C and daunorubicin. About 25% of complete responders will have extended long-term survival and may be cured. Therefore we treated patients having acute myelogenous leukemia with AD(7+3) regimen and analyzed factors complete remission rate, remission duration, and survival duration.
MATERIALS AND METHODS
Induction therapy; Thirty seven patients with previously untreated acute myelogenous leukemia treated with AD(7+ 3) regimen(ara-C, 200 mg/m2/d by continuous infusion for seven days, and daunorubicin, 45 mg/m2/d for 3 days). The second course of therapy was AD(5+2), if the patients failed to enter remission. Consolidation therapy; three cycles of consolidation chemotherapy were administrated with at least 4 week interval following remission. Course 1; ara-C at 100 mg/m2 by continuous infusion every 12 hour for five days, 6-thioguanine at 100 mg/m2/day orally for 5 days. Course 2; ara-C is same as course 1, vincristine at 1.2 mg/m2(maximum 2 mg) by bolus injection for 1 day, prednisolone at 40 mg/m'(maximum 60 mg) orally for 5 days. Course 3; ara-C is same as course 1, daunorubicin at 45 mg/m2 by 1 hour infusion for 2 days.
RESULT
62.2 percent of the 37 patients entered complete remission. The remission duration for all patients in complete remission ranged from 2 months to 63+ months, with the median of 15.1 months. The median duration of survival in complete responder group was 23.3 months. Among various prognostic factors, females and groups with normal chromosome and t(8;21) or t(15;17) had significantly higher complete remission rate than males and groups with other chromosomal abnormalities, respectively. Factors influencing on survival duration were female, normal chromosome, t(8;21) or t(15;17), Auer rod-positive, and peripheral blast % less than 50% at diagonosis. Groups with Auer rod-positive, normal chromosome, and t(8;21) or t(15;17) also had significantly longer remission duration.
CONCLUSION
Combination chemotherapy with cytosine arabinoside and daunorubicin is a effective regimen for acute myelogenous leukemia as much as other regimen for acute myelogenous leukemia. Further clinical trials for effective treatment regimen are necessary to increase the complete remissioin rate.

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Original Article

Study on Growth Suppression Effect of Vetamin D3 Mediated by Transfrorming Growth Factor-B1(TGF-B1) in Acute Myelogenous Leukemic Cell: Chul Won Jung, Sang Jae Lee, Myung Joo Ahn, Tae Joon Jung, In Soon Kim, Il Young Choi, Jae Koo Seol, Eun Sil Kim, Byung Kook Kim, Young Yeol Lee; J Korean Cancer Assoc. 1998;30(4):827-841.

Abstract PDF: PURPOSE
Vitamin D3 was shown to arrest the growth of acute myelogenous leukemic cells and transforming growth factor- B1 (TGF- B1) was reported to be involved in the mechanism of vitamin D3. We studied the growth inhibitory effect of 1,25(OH)2-vitamin D3(C) and its analogue (EB1089) in leukemic cell lines and the changes in the secretion or the activation of TGF-B1 in the supernatant and the status of TGF-B1 type II receptor.
MATERIALS AND METHODS
Growth inhibition by vitamin D3 and TGF-B1 in 5 leukemic cell lines (HEL, HL-60, U937, KG-1, K562) were assessed with clonogenic and [3H]thymidine assay respectively. TGF-B type II receptor status was examined by Southern and Northern blotting. The concentrations of TGF- B1 in the supernatant were quantitated by enzyme immunoassay.
RESULTS
The growth of HEL, HL-60, U937 were inhibited in a dose-dependent fashion by both C and EB1089, more markedly by the latter. Anti-TGF-B neutralizing antibody partially reversed the growth inhibition. TGF-B1 markedly inhibited the growth of HEL, U937, KG-1, SNU-16 dose dependently while HL-60 and K562 showed no growth inhibition. HEL secreted latent TGF- 1 and HL-60 activated latent TGF- B1 or secreted active TGF-B1 irrespective of the treatment with vitamin D3. In U937, vitamin D3 increased the concentration of both active and latent TGF-B1. Deletion or abnormal expression of TGF- B type II receptor gene was not found in the 5 cell lines examined.
CONCLUSION
Vitamin D3 has various pattern of growth inhibition in acute myelogenous leukemia and inhibits the growth of some cell lines by secretion or activation of TGF-B1. Abnormality of TGF-B type II receptor DNA or mRNA seems to be rare.

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Case Report

A Case of Acute Lymphocyic Leukemia with Bilarteral Breast Masses: Hun Sik Jeong, Hong Ghi Lee, Jong Tae Lee, Won Seng Kim, Sung Soo Yoon, Won Ki Kang, Keun Chil Park, Jeong Hyun Yang, Chan Hyung Park; J Korean Cancer Assoc. 1998;30(1):198-202.

Abstract PDF: We present a case of a 47-year-old female with acute lymphocytic leukemia with granulocytic sarcoma in her breasts. The presenting symptom was palpable bilateral breast masses. She underwent fine needle biopsy, and a diagnosis of granulocytic sarcoma was rendered. A bone marrow examination revealed acute lymphocytic leukemia. She received a course of induction chemotherapy with Daunorubicin, Vincristine, Prednisolone, and L-asparaginase.

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