• Clinical and Experimental Pediatrics
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• v.56 no.3
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• pp.130-134
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• 2013

Purpose: Anthracyclines have been utilized in the treatment of children with acute lymphoblastic leukemia (ALL). Recent studies have shown that anthracyclines may induce toxicity in the vascular endothelium. This study was performed using brachial artery reactivity (BAR) to evaluate vascular endothelial function in ALL patients who were treated with anthracycline chemotherapy. Methods: We included 21 children with ALL who received anthracycline chemotherapy and 20 healthy children. The cumulative dose of anthracyclines in the ALL patients was $142.5{\pm}18.2/m^2$. The last anthracycline dose was administered to the patients 2 to 85 months prior to their examination using BAR. The diameter of the brachial artery was measured in both groups using echocardiography, and BAR was calculated as the percentage change in the arterial diameter after release of the cuff relative to the baseline vessel diameter. Results: In the anthracycline-treated group, BAR was observed to be $3.4%{\pm}3.9%$, which was significantly lower than that observed in the control group ($12.1%{\pm}8.0%$, P<0.05). The time elapsed after the last anthracycline treatment and the age at the time of treatment did not affect the change in BAR (P =0.06 and P =0.13, respectively). Conclusion: These results provided evidence that treatment of ALL patients with anthracycline results in endothelial dysfunction. A larger cohort study and a longer follow-up period will be required to clarify the relationship between endothelial dysfunction resulting from anthracycline treatment for childhood ALL and occurrence of cardiovascular diseases later in life.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4843-4846
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• 2014

Background: Acute lymphoblastic leukemia (ALL) is most common in childhood. Inhibin (a non-steroidal glycoprotein hormone of gonadal origin) can be used as marker of fertility. The current study was conducted to evaluate inhibin levels in ALL patients and to estimate its correlation with some antioxidants in these in comparison with control subjects. Materials and Methods: This study was conducted on sixty patients with ALL and thirty children as controls. Fasting blood samples were taken from each subject and analyzed for haemoglobin, serum protein, vitamin E and C, in addition to glutathione and inhibin. Results: The results of the study showed highly significant decreases (p<0.001) in haemoglobin, glutathione and inhibin levels with significant decreases (p<0.05) in serum protein and vitamin E levels for patients group in comparison with controls while there was no significant differences in vitamin C. Moreover, there were significant correlations between inhibin levels and serum protein, glutathione and both vitamins (E and C) in the ALL patient group (r= 0.81, 0.80, 0.77 and 0.69, respectively). Conclusions: The present results indicated infertility in patients with ALL demonstrated by low inhibin level as a consequence of abnormality in anti-oxidative metabolism due to the cancer process. So, it can be suggested the need for routine measurement of inhibin for leukemic patients to estimate the action of hormones of gonadal origin.

• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1260-1265
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• 2003

Purpose : In 1970, the Berlin-Frankfurt-Munster(BFM) group introduced an intensification therapy after remission induction to reduce relapse of acute lymphoblastic leukemia(ALL) in childhood. Delayed intensification(DI) phase has been included for treatment of ALL in our hospital since the mid-1990s. The purpose of this study is to evaluate the outcome with vs. without DI phase and the outcome with two vs. one DI phase for intermediate risk patients. Methods : One hundred and thirty nine children with ALL who were treated at the Department of Pediatrics of Wonju Christian Hospital and Yonsei University Medical Center between March, 1990 and July, 2002 were analysed retrospectively. Results : Thirty-eight patients were treated with a DI phase, and 101 patients were treated without a DI phase. Among the DI patients, seven patients were treated with a double DI phase. Five-year overall survival(OS) in the low, intermediate, and high risk groups were 68%, 66% and 58%, respectively. 5-year OS in DDI, DI, and control were 95%, 86% and 40%, respectively. In the low risk group, 5-year event free survival(EFS) in DI, and control were 94% and 58%, respectively. Conclusion : Delayed intensification improved EFS on childhood ALL in all risk groups.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3541-3546
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• 2014

TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3515-3519
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• 2016

Background: In Thailand, a national treatment protocol for childhood leukemia and lymphoma (LL) was implemented in 2006. Access to treatment has also improved with the National Health Security system. Since these innovations, survival of childhood LL has not been fully described. Materials and Methods: Trends and survival of children under 15 with childhood cancers diagnosed between 1993 and 2012 were investigated using the hospital-based data from the Khon Kaen Cancer Registry, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. Childhood cancers were classified into 12 diagnostic groups, according to the ICCC based on the histology of the cancer. Survival rates were described by period, depending on the treatment protocol. For leukemias and lymphomas, survival was assessed for 3 periods (1993-99, 2000-5, 2006-12) while for solid tumors it was for 2 periods (before and after 2000). The impacts of sex, age, use of the national protocol, and catchment area on leukemia and lymphoma were evaluated. Overall survival was calculated using the Kaplan-Meier method while the Cox proportional hazard model was used for multivariate analysis. Trends were calculated using the R program. Results: A total of 2,343 childhood cancer cases were included. Survival for acute lymphoblastic leukemia (ALL) from 1993-9, 2000-5, and 2006-12 improved significantly (43.7%, 64.6%, and 69.9%). This was to a lesser extent true for acute non-lymphoblastic leukemia (ANLL) (28.1%, 42.0%, and 42.2%). Survival of non-Hodgkin lymphoma (NHL) also improved significantly (44%, 65.5%, and 86.8%) but not for Hodgkin disease (HD) (30.1%, 66.1%, and 70.6%). According to multivariate analysis, significant risk factors associated with poor survival in the ALL group were age under 1 and over 10 years, while not using the national protocol had hazard ratios (HR) of 1.6, 1.3, and 2.3 respectively. In NHL, only non-use of national protocols was a risk factor (HR 3.9). In ANLL and HD, none of the factors influenced survival. Survival of solid tumors (liver tumors, retinoblastomas) were significantly increased compared to after and before 2000 while survival for CNS tumors, neuroblastoma and bone tumors was not changed. Conclusions: The survival of childhood cancer in Thailand has markedly improved. Since implementation of national protocols, this is particularly the case for ALL and NHL. These results may be generalizable for the whole country.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2285-2289
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• 2012

Multidrug resistance (MDR) is a main cause of failure in the chemotherapeutic treatment of malignant disorders. One of the well-known genes responsible for drug resistance encodes the multidrug resistance-associated protein (MRP1). The association of MRP1 with clinical drug resistance has not systematically been investigated in Iranian pediatric leukemia patients. We therefore applied real-time RT-PCR technology to study the association between the MRP1 gene and MDR phenotype in Iranian pediatric leukemia patients. We found that overexpression of MRP1 occurred in most Iranian pediatric leukemia patients at relapse. However, no relation between MRP1 mRNA levels and other clinical characteristics, including cytogenetic subgroups and FAB subtypes, was found.

• Clinical and Experimental Pediatrics
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• v.55 no.3
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• pp.100-106
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• 2012

Purpose: The survival rate for childhood acute lymphoblastic leukemia (ALL) has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR). Methods: Fifty-three ALL patients (42 men, 79%) who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%). Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD), relapse, 1-year transplant-related mortality (TRM), disease-free survival (DFS), and overall survival (OS). Results: Cumulative incidences of acute GVHD (grade 2 or above) and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was $45.2{\pm}6.8%$ and $48.3{\pm}7%$, respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis ($p$=0.010). The rates of relapse and 1 year TRM were $28.9{\pm}6.4%$ and $26.4{\pm}6.1%$, respectively, and unrelated donor HSCT ($p$=0.002) and HLA mismatch ($p$=0.022) were significantly correlated with increased TRM in univariate analysis. Conclusion: In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

• Childhood Kidney Diseases
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• v.21 no.1
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• pp.21-25
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• 2017

Severe hypercalcemia is rarely encountered in children, even though serum calcium concentrations above 15-16 mg/dL could be life-threatening. We present a patient having severe hypercalcemia and azotemia. A 14-year-old boy with no significant past medical history was referred to our hospital with hypercalcemia and azotemia. Laboratory and imaging studies excluded hyperparathyroidism and solid tumor. Other laboratory findings including a peripheral blood profile were unremarkable. His hypercalcemia was not improved with massive hydration, diuretics, or even hemodialysis, but noticeably reversed with administration of calcitonin. A bone marrow biopsy performed to rule out the possibility of hematological malignancy revealed acute lymphoblastic leukemia. His hypercalcemia and azotemia resolved shortly after initiation of induction chemotherapy. Results in this patient indicate that a hematological malignancy could present with severe hypercalcemia even though blast cells have not appeared in the peripheral blood. Therefore, extensive evaluation to determine the cause of hypercalcemia is necessary. Additionally, appropriate treatment, viz., hydration or administration of calcitonin is important to prevent complications of severe hypercalcemia, including renal failure and nephrocalcinosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7989-7993
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• 2014

Background: The Khon Kaen Cancer Registry (KKCR) was established in 1984. Previous population-based incidences and survivals of childhood cancer in Thailand were determined using a short cancer registration period. Materials and Methods: Data were retrieved of all children residing in Khon Kaen, between 0-15 years, diagnosed as having cancer and registered in the KKCR (1985-2009). The follow-up censored date was December 31, 2012. The childhood cancers were classified into 12 diagnostic groups, according to the International Classification of Childhood Cancer. The incidence was calculated by the standard method. Survival of childhood cancer was investigated using the KKCR population-based registration data and overall survival calculated using the Kaplan Meier method. Results: In the study period, 912 newly diagnosed cases of childhood cancer were registered. The respective mean and median age was 6.4 (SD=4.6) and 6 (0-14) years. The age-peak for incidence was 0-4 years. The age-standardized rate (ASR) was 83 per million. Leukemia was the most common cancer (N=360, ASR 33.8) followed by neoplasms of the central nervous system (CNS, N=150, ASR 12.8) and lymphoma (N=79, ASR 7.0). The follow-up duration totaled 101,250 months. The death rate was 1.11 per 100 person-months (95%CI: 1.02 -1.20). The 5-year overall survival was 52% (95%CI: 53-56.9) for all cancers. The respective 5-year overall survival for (1) acute lymphoblastic leukemia (ALL), (2) acute non-lymphoblastic leukemia (ANLL), (3) lymphoma, (4) germ cell tumors, (5) renal tumors, (6) retinoblastoma, (7) soft tissue tumors, (8) CNS tumors, (9) bone tumors, (10) liver tumors, and (11) neuroblastoma was (1) 51%, (2) 37%, (3) 63%, (4) 74%, (5) 67%, (6) 55%, (7) 46%, (8) 44%, (9) 36%, (10) 34%, and (11) 25%. Conclusions: The incidence of childhood cancer is lower than those of western countries. Respective overall survival for ALL, lymphoma, renal tumors, liver tumors, retinoblastoma, soft tissue tumors is lower than that reported in developed countries while survival for CNS tumors, neuroblastoma and germ cell tumors is comparable.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9495-9498
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• 2014

Background: The difference in prognosis of adult and childhood acute lymphoblastic leukemia (ALL) can be attributed largely to variation in cytogenetic abnormalities with age groups. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of the patients. Aim and Objectives: To determine the frequency of cytogenetic abnormalities in Pakistani adult patients with ALL in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (${\geq}15$years old) diagnosed at Aga Khan University from January 2006 to June 2014 was performed. Phenotype (B/T lineage) was confirmed in all cases by flow cytometry. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 166 patients were diagnosed as ALL during the study period, of which 151 samples successfully yielded metaphase chromosomes. The male to female ratio was 3.4:1. The majority (n=120, 72.3%) had a B-cell phenotype. A normal karyotype was present in 51% (n=77) of the cases whereas 49% (n=74) had an abnormal karyotype. Of the abnormal cases, 10% showed Philadelphia chromosome; t(9;22)(q34;q11.2). Other poor prognostic cytogenetic subgroups were t(4;11)(q21;q23), hypodiploidy (35-45 chromosomes) and complex karyotype. Hyperdiploidy (47-57 chromosomes) occurred in 6.6%; all of whom were younger than 30 years. Conclusions: This study showed a relatively low prevalence of Philadelphia chromosome in Pakistani adults with ALL with an increase in frequency with age (p=0.003). The cumulative prevalence of Philadelphianegative poor cytogenetic aberrations in different age groups was not significant (p=0.6).