• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1127-1130
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• 2013

Background: The standard national protocol for treatment of acute lymphoblastic leukemia (ALL) in children was implemented in 2006. A systematic evaluation of the treatment outcome is needed. This study examined the relapse-free survival among childhood ALL cases treated with this protocol and related factors. Materials and Methods: A descriptive study was conducted in children aged between 0-15 years, newly diagnosed with ALL between March 2006 and March 2011 at Srinagarind Hospital, Department of Pediatrics, Faculty of Medicine, Khon Kaen University. The patients were treated on the basis of stratified risk as per the Thai national protocol. Data were compiled from the hospital records. The Kaplan-Meier method was used to describe relapse-free survival and the Cox proportional hazard model to investigate the associated factors. Results: Of the 103 children recruited, 86 (83.5%) achieved complete remission. The total follow-up time was 3132.5 person-months. Eighteen (20.9%) relapsed. The incidence density was 0.6 per 100 person-months (95%CI: 0.4, 0.9). The respective relapse-free rates at 1, 3 and 5 years were 93.0% (95%CI: 85.1, 96.8), 84.5% (95%CI: 74.0, 90.9) and 64.1% (95%CI: 45.6, 77.8). A factor associated with the relapse-free rate was age under 1 year (HR=6.0; 95%CI: 1.1, 33.8). Conclusions: The rate of being relapse-free in ALL children treated under the Thai national protocol at Srinagarind Hospital was better than with former protocols; however, it is still not as good as in developed countries. Further review of the treatment approach of ALL is needed.

• Clinical and Experimental Pediatrics
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• v.54 no.3
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• pp.95-105
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• 2011

Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

• Clinical and Experimental Pediatrics
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• v.54 no.3
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• pp.106-110
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• 2011

In pediatric patients with acute lymphoblastic leukemia (ALL), the Philadelphia chromosome translocation is uncommon, with a frequency of less than 5%. However, it is classified as a high or very high risk, and only 20-30% of Philadelphia chromosome-positive (Ph+) children with ALL are cured with chemotherapy alone. Allogeneic hematopoietic stem cell transplantation from a closely matched donor cures 60% of patients in first complete remission. Recent data suggest that chemotherapy plus tyrosine kinase inhibitors (TKIs) may be the initial treatment of choice for Ph+ ALL in children. However, longer observation is required to determine whether long-term outcome with intensive imatinib and chemotherapy is indeed equivalent to that with allogeneic related or alternative donor hematopoietic stem cell transplantation (HSCT). Reports on the use of second-generation TKIs in children with Ph+ ALL are limited. A few case reports have indicated the feasibility and clinical benefit of using dasatinib as salvage therapy enabling HSCT. However, more extensive data from clinical trials are needed to determine whether the administration of second-generation TKIs in children is comparable to that in adults. Because Ph+ ALL is rare in children, the question of whether HSCT could be a dispensable part of their therapy may not be answered for some time. An international multicenter study is needed to answer the question of whether imatinib plus chemotherapy could replace sibling allogeneic HSCT in children with Ph+ ALL.

• Korean Journal of Clinical Pharmacy
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• v.1 no.1
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• pp.1-7
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• 1991

Folates are involved in a variety of important biosynthesis by way of donating one carbon unit. Since folate metabolism was well understood a number of antifol have been developed. Among these antifols, aminopterin was first used in the treatment of childhood leukemia. However due to its toxicity and purity problems. it was immediately replaced by another antifols. methotrexate (MTX). MTX is shown to be active against various malignancies including leukemia breast cancer, osteogenic sarcoma, and head and neck cancer. Clinically, MTX therapy is divided into 3 categories. depeding on the dose administered; low-dose is defined as doses < $80\;mg/m^2$ intermediate-dose as doses $\geqq\;80\;mg/m^2$ and < $1000\;mg/m^2$ and high-dose as doses $\geqq\;1000\;mg/m^2$. Leucovorin should be administered to minimize MTX toxicities when MTX doses are greater than $80-100\;mg/m^2$. The clinical pharmacokinetics (ADME) of MTX is discussed in this text.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.431-435
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• 2015

Background: Although childhood cancer is a rare disease, 100,000 children younger than 15 years of age die from cancer each year, the majority of them in developing countries. More data need to be gathered and published particularly in developing countries to better understand the scale of the problem. Aims: This study aimed to describe the patterns of childhood cancers in Saudi Arabia over a period of ten years (1999-2008). Materials and Methods: This descriptive retrospective study was based on secondary data from the Saudi Cancer Registry from 1999 to 2008. All Saudi cases (both genders), under the age of 15 years, who were diagnosed with cancer during the study period, were included in this study. Results: Childhood cancer in Saudi Arabia, in the period between 1999 and 2008, accounted for about 8% of total cancer cases. The most common encountered cancers were leukemia (34.1%), followed by lymphoma (15.2%), brain (12.4%), and kidney cancers (5.3%). The overall incidence of childhood cancers increased from 8.8 per 100,000 in 1999 to 9.8 per 100,000 in 2008. The incidence rates of cancers per 100,000 in the years 1999 and 2008 were generally higher among males, (9.4 and 11.5 in males vs. 8.3 and 8.1 in females). The highest incidence rate in the surveyed years was apparent in the birth to age 4 years group. Conclusions: Cancer is an important public health problem in Saudi Arabia and a major ascending contributor to mortality and morbidity in children. More studies are required to describe the patterns of childhood cancers and related risk factors in Saudi Arabia.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.606-612
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• 2007

Since the introduction of chemotherapy for the treatment of childhood leukemia more than 50 years ago, the results of childhood cancer have improved dramatically. The 5-year survival rate of disease, many of which were uniformly fatal in the prechemotherapy era, reached to more than 75%. This remarkable improvement in survival is a direct result of the incorporation of chemotherapeutics into treatment regimens that previously relied only on surgery or radiotherapy for the primary tumor. The multimodality approach, which integrates surgery and radiotherapy to control local disease with chemotherapy to eradicate systemic or metastatic disease, has become the standard approach to treating most childhood cancers. The overall improvement in outcomes in childhood solid tumors has been related to the development of multidisplinary cooperative studies that has permitted the development of well-designed tumor treatment protocols characterized by uniform staging criteria, sharing informations in pathologic classification, uniform methods for tumor markers, oncogenes, and other biologic and genetic factors. Important advances in the biologic study of cancer and its genetic basis led to a number of observations that impact directly on the management of childhood solid tumors. Identification of specific genes, oncogenes, tumor markers, and other biologic and pathologic factors plays an important role in both staging and clarifying the risk categorization of individual patients. Treatment of the patient is influenced by the recognition of specific risk factors. This knowledge has resulted in a change in the approach to care based not only on staging criteria, but also on risk-based management. This concept uses various risk factors of outcomes. Risk-based management allows for each patient to maximize survival, minimize long-term morbidity and improve the quality of life, especially for children's growth and development.

• 대한예방의학회:학술대회논문집
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• 1993.10a
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• pp.21-22
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• 1993

• Archives of Pharmacal Research
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• v.29 no.1
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• pp.80-87
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• 2006

Leukemias are common worldwide. Wilms'tumor1 (WT1) protein is highly expressed in leukemic blast cells of myeloid and lymphoid origin. Thus, WT1 mRNA serves as a tumor marker for leukemias detection and monitoring disease progression. Curcumin is well known for its anticancer property. The objective of this study was to investigate the effect of curcumin on WT1 gene expression in patient leukemic cells. The leukemic cells were collected from 70 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period July 2003 to February 2005. There were 58 cases of acute lymphoblastic leukemia (ALL), 10 cases of acute myeloblastic leukemia (AML), and 2 cases of chronic myelocytic leukemia (CML). There were 41 males and 29 females ranging from 1 to 15 years old. Leukemic cells were cultured in the presence or absence of 10 mM curcumin for 48 h. WT1 mRNA levels were determined by RT-PCR. The result showed that curcumin reduced WT1 gene expression in the cells from 35 patients (50%). It affected the WT1 gene expression in 4 of 8 relapsed cases (50%), 12 of 24 cases of drug maintenance (50%), 7 of 16 cases of completed treatment (44%), and 12 of 22 cases of new patients (54%). The basal expression levels of WT1 gene in leukemic patient cells as compared to that of K562 cells were classified as low level (1-20%) in 6 of 20 cases (30%), medium level (21-60%) in 12 of 21 cases (57%), and high level (61-100%) in 17 of 23 cases (74%). In summary, curcumin decreased WT1 mRNA in patient leukemic cells. Thus, curcumin treatment may provide a lead for clinical treatment in leukemic patients in the future.

• Journal of Environmental Health Sciences
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• v.45 no.3
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• pp.203-212
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• 2019

Objective: A total of five students at same middle school were reported to be diagnosed with pediatric leukemia (n=2), non-Hodgkin's lymphoma (NHL, n=1) and aplastic anemia (n=2) between 2016 and 2017. The aims of this study are to assess exposure to environmental hazardous agents known to be associated with the risk of leukemia and to examine whether the environment of school is associated with the risk leukemia. Method: A total of 11 environmental agents causing childhood leukemia were monitored using international certified method in schools where patients had ever attended. Radon & Thoron detector was used to monitor real-time airborne radon and thoron level ($Bq/m^3$). Clinician interviewed two among nine patients who agreed to participate in this study in order to examine the association of demographic and genetic factors by individually. Leukemia, NHL, and aplastic anemia were grouped into lymphohematopoietic disorder (LHP). Results: Except for airborne radon level, no environmental agents in school and household where patients may be exposed were found to higher than recommended airborne level. Clinical investigation found no individual factors that may be associated with the risk of LHP. Higher airborne radon level than Korea EPA's airborne radon criteria ($148Bq/m^3$) was monitored at most of several after-class room of one elementary school, where two leukemia patients graduated. Significant radon level was not monitored at class-room. Significant exposure to radon of patients was not estimated based on time-activity pattern. Conclusions: Our results have concluded that there have been no environmental factors in school and household environment that may be associated the risk of LHP.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7343-7350
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• 2015

Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic and prognostic information with a direct impact on patient management. Detection of chromosome abnormalities by conventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant role in assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition of genetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the last twelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomal abnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital. G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% of cases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidy group (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidy group (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) with abnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed by t(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1 fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application of the FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis with ALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomal aberrations along with non-specific rearrangements and their association with specific immunophenotypes. This study pool is representative of paediatric/adult ALL patients in Oman.