Cancer Research and Treatment

Original Articles

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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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.

Citations

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Swathi Putta, Santhosh Kumar Chinnaiyan, Ramadevi Korni, Venkata Radha Gadela
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Proteomic analysis reveals chromatin remodeling as a potential therapeutical target in neuroblastoma
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
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Revista Médicas UIS.2024;[Epub] CrossRef
Clofarabine

Reactions Weekly.2023; 1958(1): 155. CrossRef
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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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.

Citations

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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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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.

Citations

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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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A Study on the Significance of Peripheral T-lymphocyte Subsets and Mitogen-induced Lymphocyte Prolicaraction in Acute Lymphoblastic Leukemia in Childhood: Sang Hyun Byun, Jong Jin Seo, Young Hun Chung; J Korean Cancer Assoc. 1990;22(2):257-267.

Abstract PDF: To evaluate the relationship between peripheral blood T-lymphocyte subsets, mitogen-induced lymphocyte proliferation and the outcome of acute lymphoblastic leukemia in childhood, the authors studied 15 cases of acute Iymphoblastic leukemia in childhood. The results were as follows: 1 I Percent peripheral lymphocyte and percent CDS+ cells showed no significant difference between total patient group and control group, while percent CD4+ cells was significantly decreased in total patient group compared to control group. But no significant difference was found between patient subgroups 2) Total counts of CD4+ cells and CD8+cells showed no significant difference between patient subgroups. 3) The ratio of CD4+cells and CDB+ cells showed no significant difference between patient subgroups, but more cases with the ratio less than 1.0 were found among total patient group compared to control group. 4) The stimulation indices of PHA and Con-A were significantly decreased in total patient group (p<0.05, p<0.005) compared to control group, but no significant difference was observed between patient subgroups. 5) The unstimulated 3[H]-thymidine uptake showed no significant relationship between patient subgroups. 6) The distribution of T-lymphocyte subsets showed no significant relationship with the stimula- tion index of PHA and Con-A. These results showed that the children with acute lymphoblastic leukemia have depressed cellular immune functions tested with T-lymphocvte subsets and mitagen-induced lymphocyte proliferation assay. But these results can not be regarded as one of prognostic factors of acute lymphoblastic leukemia in childhood unless there are additional longterm data indicating the T-cell mediated immune functions are related to the outcome of acute lymphoblastic leukemia in childhood.

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Treatment of Childhood Acute Lymphoblastic Leukemia Diagnosed Jan . , 1978 Through Dec . , 1987 : Comparison between Standard - Risk and High - Risk Groups: Soon Ki Kim, Hee Young Shin, Hyo Seop Ahn; J Korean Cancer Assoc. 1990;22(3):539-549.

Abstract PDF: Of 328 children who were diagnosed as acute lymphoblastic leukemia at the Department of Pediatrics. Seoul National University Hospital from Jan., 1978 through Dec., 1987, 211 patients above one year af age were evaluable for induction chemotherapy. The leukemias were classified as standard risk (SR), comparison group (who had high-risk prognostic factors, but had been treated with standard regimen), or high- risk (HR) leukemia according to the prognostic criteria at diagnosis. Three regimens were compared and the results were as follows. 1) The complete remission (CR) rate was 97.1%(133/137), 81.0%(34/42) and 90.6%(29/32) in SR, comparison group. and HR group, respectively. And significant difference in the CR rate was seen between SR group and comparison group (p= 0.0001). 2) Of the patients remained in remission follow-up of each group showed 56.8% 5-yr disease-free survival (DFS)(+-5.9%, median follow-up 30 mo) in SR, 35.5% (+-9.1%, median 24 mo) in comparison group, and 76.0%(+- 8.5%, median 24 mo) in HR group. And significant difference in the 5yr-DFS rate were observed be(ween SR and comparison group (P = 0.007), between HR and comparison group (p = 0.002), respectively. 3) Induction failure was due to infection (n=2) bleeding (n=1) or uric acid nephropathy (n= 1) in SR drug resistance (n=3), infection (n=2), bleeding (n=2), or combind infection and bleeding (n=1) in comparison group, and bleeding (n=2) or infection (n= 1) in HR. Of the patients who were on maintenance chemotherapy in complete remission, 11 died due to infection: menigitis or meningoencephalitis (n=4), disseminated varicella (n=3), Pneumocystis carinii pneumonia (n=2), and sepsis (n=2). 4) In SR group, 29 patients experienced relapse: BM(n=18), CNS(n=3), BM and CNS(n=4), and testes (n=4). Two- third (n = 19) of them relapsed between 6mo to 2yr after initial remission. In comparison graup, 20 relapsed: BM (n= 10), CNS(n=2), BM and CNS (n=3), testes (n=4), and testes and CNS(n =1), Mostly they relapsed within the first 2 years after remission. In HR group, all patients (BM 3 and CNS 1) experienced relapse from 1 yr to 1 1/2 yr after initial remission.

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Effects of cancer nervous System Irradiation on Neuropsychologic Functioning in Long - term Survivors of Childhood Acute Lymphoblastic Leukemia: Ji Eun Choi, Hee Young Shin, In One Kim, Kyung Mo Yeon, In Young Chae, Soo Churl Cho, Yong Seung Hwang, Hyo Seop Ahn; J Korean Cancer Assoc. 1995;27(2):303-316.

Abstract PDF: Long-term adverse neuropsychologic sequelae are frequently observed in pediatric patients treated for acute lymphoblastic leukemia(ALL). In this study, 10 children in continuous com- plete remission from ALL were given tests of IQ, neuropsychologic assessment, waking EEG, brain MRI to assess neuropsychologic functioning minimum 2 years after CNS prophylaxis. All children were free of CNS disease at diagnosis and had received CNS prophylactic treatment with 1,800 cGy cranial irradiation plus intrathecal methotrexate. Male patients had a significant decline in coding compared with female patients(P<0.01) and those evaluated beyond age of 10-year-old had a greater decline in performance IQ compared with those evaluated under age of 10-year-old(P<0.01). One of the 10 children(10%) showed white matter changes on MRI attributable to therapy. All children had no significant lower mean IQ, but lower achievement with regard to arithmetic skills, picture arrangement than other tests. We conclude that prophylactic CNS therapy may cause cognitive dysfunctions and the white matter changes but its value and significance during follow-up should be assessed in well designed longitudinal research studies.

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cDNA Sequencing of the Sh Region of Phospholipase C-γ1 from Human Cervix Carcinomas Using RT-PCR: Yee Sook Cho, Yong Ki Baek, Young Min Song, Byung Chan Oh, Uh Hyun Kim; J Korean Cancer Assoc. 1995;27(2):316-322.

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