• 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.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2001.09a
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• pp.25-25
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• 2001

An example of lymphoblastic lymphosarcoma was diagnosed in a 7-year-old male brown bear (Ursus arctos) that died after having a 7-month history of depression, anorexia and watery diarrhea. Grossly the mesenteric lymph nodes were enlarged to approximately 4 to 6 times their normal size and histologically diagnosed as lymphoblastic lymphosarcoma. The small intestinal mucosa was corrugated and had severe mural thickening due to infiltrated neoplastic cells. Hepatic metastasis was also noted. the mother of this bear which died at the age of 20 also had similar gross changes on necropsy, but histological examination was not performed at that time and therefore the exact type of neoplasm remained to be determined. Since the daughter also died of neoplasm, genetic factor could be suspected in this family. This is the first reported case of lymphosarcoma in Ursidae in Korea. As an incidental finding, endogenous lipid pneumonia was noted in the lung.

• Journal of the Korean Society of Radiology
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• v.83 no.2
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• pp.394-399
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• 2022

While extramedullary relapse of leukemia could occur, the parotid gland is a rare site of recurrence. Extramedullary relapse involving the parotid gland could be mistaken for other diseases. Moreover, the diagnosis of this disease is often delayed due to its rarity. Herein, we present a case of extramedullary relapse of acute lymphoblastic leukemia involving the parotid gland.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4581-4585
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• 2012

Fms-like tyrosine kinase 3 (FLT3) performs a vital role in the pathogenesis of hematopoietic malignancies. Therefore in recent times, the focus of several studies was on use of FLT3 as a prognostic marker. The present study investigated the molecular characterization and incidence of FLT3 mutations in acute leukemia patients in Pakistan. A total of 55 patients were studied, of which 25 were suffering from acute lymphoblastic leukemia (ALL) and 30 were suffering from acute myeloid leukemia (AML). The polymerase chain reaction demonstrated FLT3/ITD mutations in 1 (4%) of 25 ALL patients, a male with the L2 subtype. In AML cases the rate was 4 (13.3%) of 30, three males and one female. The AML-M4 subtype was found in three and the AML M2 subtype in the other. In the AML cases, a statistically significant (p=0.009) relationship was found between WBC (109/L) and FLT3/ITD positivity. However, no significant relationship was found with other clinical parameters (p>0.05). In acute myeloid leukemia (AML) $FLT3/ITD^+$ mutation was more prevalent in elderly patients 31-40 age groups, 21-30 and 51-60 age groups respectively. In acute lymphoblastic leukemia (ALL) statistically no significant relationship was found between clinical features and FLT3/ITD positivity (p>0.05). However, in acute lymphoblastic leukemia (ALL) $FLT3/ITD^+$ mutation was more commonly found in age groups of 21-30.

• Clinical and Experimental Pediatrics
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• v.53 no.11
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• pp.957-964
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• 2010

Purpose: Our study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells. Results: Thirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with ${\geq}1%$ leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9 % [18.7%] vs. 92.0% [5.4%], $P$=0.004). Stratification into 3 MRD groups (${\geq}1%$, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, $P$=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance. Conclusion: An MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9961-9966
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• 2014

Background: Some reports have suggested that chronic myeloid leukemia (CML) patients have a higher prevalence of M-bcr than acute lymphoblastic leukemia (ALL) patients, which show a higher prevalence of m-bcr. However, the relationship between BCR-ABL subtypes and progression of CML and ALL remains unclear. Materials and Methods: 354 CML chronic phase (CML-CP) patients, 26 CML blastic phase (CML-BP) patients and 72 ALL patients before treatment with BCR-ABL positive were recruited for blood routine examination and bone marrow smear cytology. Some 80 CML-CP and 32 ALL patients after imatinib (IM) treatment were followed-up for BCR-ABL relative concentrations detected after treatment for 3, 6 and 9 months and 1 year. Results: Before treatment, CML-CP patients showed lower BCR-ABL relative concentrations with a higher proportion of M-bcr (42.7%) compared to CML-BP and ALL patients while ALL patients had a higher BCR-ABL relative concentration with high expression of m-bcr (51.4%). Patients with M-bcr demonstrated higher WBC counts than those with m-bcr and the mixed group and higher PLT counts were noted in the CML-CP and ALL groups. After imatinib (IM) treatment, patients with m-bcr showed higher BCR-ABL relative concentrations in both CML-CP and ALL groups. Conclusions: This study identified the BCR-ABL gene as an important factor in CML and ALL cases. The M-bcr subtype was associated more with CML while the m-bcr subtype was associated more with ALL. Patients with m-bcr seem to have a poorer response to IM in either CML or ALL patients compared to M-bcr patients.

• 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.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7523-7527
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• 2015

Background: Pediatric acute lymphoblastic leukemia (pALL) patients at King Abdulaziz Medical City represent a pure Saudi Arabian population. ETV6-RUNX1 positive pALL patients have good prognosis as compared to ETV6-RUNX1 negative counterparts. Therefore, frequencies of these two patient groups have a huge consideration in treatment strategies of pALL in a given population. Different geographical locations have been reported to have different frequencies of ETV6-RUNX1 ranging from 10% in Southeast Asia to 30% in Australia. Aim: Therefore, the objective of this study was to establish the ETV6-RUNX1 status of Saudi Arabian pALL patients and its association with clinical parameters and early remission. Materials and Methods: Clinical parameters and ETV6-RUNX1 status (using FISH technique) of pALL patients attending the Pediatric Oncology Clinic, King Abdulaziz Medical City, Riyadh from 2006 to 2011 were studied. Comparisons between ETV6-RUNX1 positive and negative groups were accomplished using chi-square test or Fisher's exact test. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC). Results: Out of 54 patients, 33 were male and 21 were females (ratio 1.57:1). B- and T-cell lineages were found in 47 (87%) and 7 (13%) patients respectively. Only 5 (9.3%) patients were ETV6-RUNX1 positive while 49(80.7%) were ETV6-RUNX1 negative. All ETV6-RUNX1 patients (100%) were of B-cell lineage and 80% (4/5) were in the 3-7 year age group. None of the ETV6-RUNX11 patients had ${\geq}5%$ blasts (no remission) at day 14 as compared with 9% in the ETV6-RUNX1 negative group (Figure 1). Conclusions: Frequency of ETV6-RUNX1 positive patients (less than 10%) in our pALL patients is much lower than reported for most European countries, North America, Australia and Japan while it is in accordance with ETV6-RUNX1 frequencies from Egypt (11.6%), Pakistan (10%), Spain (2%) and India (5-7%). This shows ethnic differences in genetics of pALL as well as higher frequencies of ETV6-RUNX1 positive pALL mostly in more industrialized countries, probably due to some industrial pollutants or westernized lifestyle.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6357-6362
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• 2013

Background: The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for the MTHFRC677T polymorphism and ALL risk. Methods: Electronic searches of PubMed and the Chinese Biomedicine database were conducted to select case-control studies containing available genotype frequencies of C677T and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of any association. Results: Case-control studies including 6,371 cases and 10,850 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had decreased risk of ALL (OR= 0.776, 95% CI: 0.687~0.877, p< 0.001) in Caucasians (OR= 0.715, 95% CI: 0.655~0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591~1.005, p= 0.055) and others (OR=0.913, 95% CI: 0.656~1.271, p= 0. 590) did not suggest an association. A symmetric funnel plot, the Egger's test (P=0.093), and the Begg- test (P=0.072) were all suggestive of the lack of publication bias. Conclusion: This meta-analysis supports the idea that the MTHFR C677T genotype is associated with risk of ALL in Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between the MTHFRC677T polymorphism and ALL.