Cross-cultural adaptation of the korean version of the minneapolis-manchester quality of life instrument-adolescent form.

We verified the reliability and validity of the Korean version of the Minneapolis-Manchester Quality of Life Instrument-Adolescent Form (KMMQL-AF) among Korean childhood cancer survivors. A total of 107 childhood cancer patients undergoing cancer treatment and 98 childhood cancer survivors who completed cancer treatment were recruited. To assess the internal structure of the KMMQL-AF, we performed multi-trait scaling analyses and exploratory factor analysis. Additionally, we compared each domains of the KMMQL-AF with those of the Karnofsky Performance Status Scale and the Revised Children's Manifest Anxiety Scale (RCMAS). Internal consistency of the KMMQL-AF was sufficient (Cronbach's alpha: 0.78-0.92). In multi-trait scaling analyses, the KMMQL-AF showed sufficient construct validity. The "physical functioning" domain showed moderate correlation with Karnofsky scores and the "psychological functioning" domain showed moderate-to-high correlation with the RCMAS. The KMMQL-AF discriminated between subgroups of different adolescent cancer survivors depending on treatment completion. The KMMQL-AF is a sufficiently reliable and valid instrument for measuring quality of life among Korean childhood cancer survivors.

Normalization of red cell enolase level following allogeneic bone marrow transplantation in a child with Diamond-Blackfan anemia.

We describe a girl with Diamond-Blackfan anemia with accompanying red cell enolase deficiency. At the age of 9 yr old, the patient received allogeneic bone marrow transplantation from her HLA-identical sister who had normal red cell enolase activity. While the post transplant DNA analysis with short tandem repeat has continuously demonstrated a stable mixed chimerism on follow-up, the patient remains transfusion independent and continues to show a steady increase in red cell enolase activity for over two and a half years following bone marrow transplantation.

Stem cell transplant in the treatment of childhood biphenotypic acute leukemia.

BACKGROUND: Many studies have found that biphenotypic acute leukemia (BAL) is associated with a poor outcome. METHODS: We retrospectively reviewed the medical records and analyzed clinicopathological data on 25 children with BAL, and correlated outcomes with prognostic factors. RESULTS: BAL constituted 4.4% of all acute childhood leukemia cases. In terms of immunophenotype, 14 patients had leukemia with myeloid plus B-lymphoid (M + B) marker, 7 with myeloid plus T-lymphoid (M + T) marker, and 4 with myeloid plus B-lymphoid and T-lymphoid (M + B + T) markers. Overall survival was superior in patients with the M + B immunophenotype (P = 0.004). Hematopoietic stem cell transplantation (HSCT) did not improve either overall survival or event-free survival compared to chemotherapy alone (hazard ratio 0.98, 95% CI 0.35-2.76, P = 0.966; hazard ratio 1.07, 95% CI 0.41-2.78, P = 0.88). Each of four patients with high-hyperdiploidy (>50 chromosomes) displayed a good treatment response and long-term overall survival even though these patients were treated with chemotherapy alone. CONCLUSIONS: Treatment outcomes in childhood BAL patients differed by immunophenotype and cytogenetics. HSCT did not offer a significantly greater survival advantage compared to chemotherapy. While these data suggest that treatment should be individualized and stratified according to biologic characteristics and prognostic factors in BAL, prospective trial data are still needed.

Long-term survival of a child with homozygous protein C deficiency successfully treated with living donor liver transplantation.

Homozygous protein C deficiency is an autosomal recessive disorder often presenting with purpura fulminans. Fresh frozen plasma and oral anticoagulation have been used in the treatment of this disease. Lately, protein C concentrate has become the treatment of choice. However, protein C concentrate is not yet widely available in many countries. We report a six-month-old girl with homozygous protein C deficiency who had suffered from frequent thrombotic episodes. She was successfully treated with living donor liver transplantation. Eight years after the transplantation, she remains symptom free. As described here, the liver transplantation offers an alternative curative treatment for children with homozygous protein C deficiency.

Adenocarcinoma of lung in never smoked children.

Except in developed countries, the incidence of lung cancer notably in women and non-smokers is rising in most parts of the world. Here, we report two children diagnosed with pulmonary adenocarcinoma at a very early age. Interestingly, both showed negative EGFR mutation despite their ethnicity, histology, never smoking status and early age. Furthermore, one had preceding pulmonary tuberculosis. In the literature, the possible association of pulmonary tuberculosis and adenocarcinoma of lung especially in non-smokers has long been debated. The two children, by far the youngest with EGFR negative adenocarcinoma of lung, form the basis of this report.

Favorable outcome in a child with EBV-negative aggressive NK cell leukemia.

Aggressive natural killer cell leukemia (ANKL) is a rare malignant disorder of mature NK cells frequently associated with Epstein-Barr virus (EBV). This malignancy is typically treated with intensive remission induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). EBV-negative ANKL and childhood ANKL, however, are not well defined and the optimal therapeutic strategy in these cases is poorly understood. Here, we present a unique pediatric EBV-negative ANKL patient who achieved a successful treatment outcome after intensified ALL type chemotherapy without allogeneic HSCT.

Safety and effects of prophylactic defibrotide for sinusoidal obstruction syndrome in hematopoietic stem cell transplantation.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT), with a mortality rate of up to 90%. We report our experience on the use of defibrotide for SOS prophylaxis in HSCT. MATERIAL AND METHODS: We retrospectively reviewed data of 49 patients who received defibrotide as SOS prophylaxis during the course of HSCT at the National Cancer Center, Goyang, Korea, between August 2005 and July 2008. RESULTS: Thirty-four patients (69.4%) were classified as a high-risk group for developing SOS. Defibrotide was well-tolerated, without any grade 3 or 4 toxicity. The median value of maximum total bilirubin within 100 days after HSCT was within the normal range. SOS was diagnosed in only 1 patient, who underwent autologous HSCT due to relapsed medulloblastoma. There was no day 100 treatment-related mortality in our study. CONCLUSIONS: Defibrotide appears to be a safe prophylaxis for SOS. This study suggests that it could be effective to use prophylactic defibrotide in advance to improve HSCT outcomes in patients at risk of SOS.

Time to establish multidisciplinary childhood cancer survivorship programs in Korea.

Improved treatment strategies and better supportive care have resulted in increased survival rates for childhood cancers. However, most of the survivors may have complex, long-term health issues. In 2004, Childhood Cancer Survivorship Study of the United States confirmed that both survivors and the medical community need to be educated about the late effects of childhood cancer treatment. Korea, with an estimated number of childhood cancer survivors of 20,000 to 25,000, faces similar challenges that the United States had experienced earlier. Despite of the tight budgetary situation on the part of government and hospitals, nationwide cohort study for Korean childhood cancer survivors was proposed and the versions of instruments to measure the quality of life of childhood cancer survivors were already validated. Nationwide registry of long-term survivors as well as the multi-center study is to be developed not only for the care of the survivors but also to raise the patient's awareness of the importance of regular follow-up. In addition to education of primary care providers regarding the survivorship, the need for special education program in the school system is emphasized.

Improved outcome in childhood ALL with intensive consolidation and hematopoietic stem cell transplant.

BACKGROUND: Despite advances in chemotherapy, the prognosis of relapsed acute lymphoblastic leukemia (ALL) remains poor. Few studies on relapsed ALL have reported the importance of intensive consolidation followed with or without allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We evaluated the post-relapse outcomes in 47 Korean children with a first marrow relapse, and analyzed the prognostic factors. RESULTS: A second complete remission (CR) was achieved in 40 patients (85.1%), and at the time of this study, second CR was maintained in 12 of these patients. The estimated 3-yr event-free survival (EFS) rate after the first marrow relapse was 29.8±6.7%, and the overall survival (OS) rate was 45.3±7.5%. We found that second remission, consolidation of pediatric oncology group chemotherapy regimen (POG 9411), and HSCT significantly affected the outcome of the disease after relapse (P<0.001; P=0.004; P=0.05). CONCLUSION: The results of our study revealed that an intensified POG 9411 consolidation chemotherapy regimen followed by HSCT can improve the outcome of patients with relapsed ALL.

High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor.

BACKGROUND: Single or tandem double high-dose chemotherapy (HDCT) was used to treat children with newly diagnosed high-risk or relapsed medulloblastoma and supratentorial primitive neuroectodermal tumor (MB/sPNET) in order to defer or avoid radiotherapy in young children. PROCEDURE: Thirty-seven HDCTs were given to 25 children with newly diagnosed high-risk or relapsed MB/sPNET. Tandem double HDCT was used for 12 of 15 patients initially intended to receive double HDCT. RESULTS: Three-year EFS (+/-SE) in 6 newly diagnosed high-risk (>3 years old), 8 newly diagnosed (<3 years old), and 11 relapsed MB/sPNET was 83.3 +/- 15.2%, 62.5 +/- 20.5%, and 29.1 +/- 15.7%, respectively. Three-year EFS for patients in CR or PR and in less than PR at first HDCT was 67.4 +/- 11.0% and 16.7 +/- 15.2%, respectively (P = 0.001). Three-year EFS in patients initially intended to receive double HDCT and single HDCT was 66.0 +/- 12.4% and 40.0 +/- 15.5%, respectively. For 19 patients in CR or PR at first HDCT, 3-year EFS was 88.9 +/- 10.5% in tandem double HDCT group, and 44.4 +/- 16.6% in single HDCT group, respectively (P = 0.037). Although four treatment-related mortalities (TRMs) occurred during 25 first HDCTs, no TRM occurred during 12 second HDCTs. In four of eight young children, craniospinal radiotherapy was successfully withheld without subsequent relapse. CONCLUSIONS: High-dose chemotherapy may improve the survival of children with newly diagnosed high-risk MB/sPNET, and, to some extent, the survival of those with relapsed MB/sPNET. Further study is necessary to elucidate the efficacy of tandem double HDCT.

Prophylactic low-dose heparin or prostaglandin E1 may prevent severe veno-occlusive disease of the liver after allogeneic hematopoietic stem cell transplantation in Korean children.

Studies investigating the effect of prophylactic drugs on hepatic veno-occlusive disease (VOD) development are rare in children that have undergone allogeneic hematopoietic stem cell transplantation (HSCT). This study examined risk factors for VOD, the effect of prophylactic low-dose heparin or lipo-prostaglandin E1 (lipo-PGE1) and the survival rate at day +100 in children undergoing allogeneic HSCT. Eighty five children underwent HSCT between June 1997 and September 2004. Patients were diagnosed and classified as having mild, moderate or severe VOD according to Seattle clinical criteria. Among 85 patients, 25 (29%) developed VOD. VOD occurred more frequently in patients receiving busulfan-based conditioning (24/65, 37%) than in those receiving TBI-based (1/10, 10%) or other (0/10, 0%) regimens (p<0.05). The incidence of VOD was lower in patients with non-malignant disease compared to those with malignant disease (p<0.05). Survival at day +100 for non-VOD patients was better than that for VOD patients (92% vs. 76%, p<0.05). No patients receiving prophylactic heparin or lipo-PGE1 were found to develop severe VOD, whereas 5 of 35 patients not receiving such prophylaxis developed severe VOD. Given severe VOD is associated with a high mortality rate, this study indicates that prophylactic heparin or lipo-PGE1 may decrease mortality in children undergoing HSCT.

Whole-body MRI of Langerhans cell histiocytosis: comparison with radiography and bone scintigraphy.

BACKGROUND: In Langerhans cell histiocytosis (LCH) evaluation of the extent of disease is one of the major predictors of patient outcome. Historically this is undertaken using plain radiography and bone scintigraphy. Recently, whole-body (WB) MRI has been reported to be useful in detecting skeletal and extraskeletal metastases in both adults and children. OBJECTIVE: To evaluate the usefulness of WB MRI in patients with LCH in comparison with plain radiography and bone scintigraphy. MATERIALS AND METHODS: In nine children (1-7 years of age; mean 3.3 years) who had a pathological diagnosis of LCH and had either plain radiography or bone scintigraphy for comparison, 43 WB MR examinations were performed. Skeletal and extraskeletal lesions of the disease on WB MRI were compared with those on plain radiography and bone scintigraphy. RESULTS: LCH showed unifocal single-system involvement in one patient, multifocal single-system involvement in three, and multifocal multisystem disease in five. WB MRI identified additional skeletal lesions in three (38%) of eight patients, compared with plain radiography, and in two (25%) of eight, compared with bone scintigraphy. WB MRI detected extraskeletal lesions of the disease in five (56%) of the nine patients exclusively, except for one patient whose lung lesions were also detected on plain radiography. In two patients, treatment was changed according to WB MRI findings. CONCLUSION: WB MRI is a useful initial and follow-up diagnostic method to assess the extent of LCH because WB MRI not only identifies more skeletal lesions of the disease than do plain radiography and bone scintigraphy, but also detects extraskeletal lesions of the disease.

Effectiveness of novel combination chemotherapy, consisting of 5-fluorouracil, vincristine, cyclophosphamide and etoposide, in the treatment of low-grade gliomas in children.

Low-grade gliomas (LGG), which account for about 30% of brain tumors in children, are usually treated with surgical excision and/or radiotherapy. For patients who have significant residual tumor after resection or relapse after radiation, the proper chemotherapy regimen has not yet been identified. Thirteen children diagnosed with LGG outside the cerebellum between January 1999 and December 2004, all of whom had significant residual tumor after surgical resection, relapsed after radiation or showed visual deterioration, were treated for 18 months with a multi-drug regimen of vincristine, etoposide, cyclophosphamide and 5-fluorouracil. Of the 7 patients who completed chemotherapy, 1 showed complete response (CR), 5 showed partial response (PR), and 1 had stable disease (SD). In 5 patients, chemotherapy was prematurely discontinued; 4 of these patients showed tumor progression and 1 had SD. One patient is still undergoing treatment. The side effects of chemotherapy were manageable. The median time to tumor response was 34 months (range, 2-82 months). The progression free survival was 67.3%. Pediatric LGG patients with residual tumor after surgery or who undergo relapse(s) may be successfully treated using our combination chemotherapy regimen.

Prognostic significance of multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression in acute leukemia.

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

Recombinant urate oxidase (Rasburicase) for the treatment of hyperuricemia in pediatric patients with hematologic malignancies: Results of a compassionate prospective multicenter study in Korea.

BACKGROUND: Hyperuricemia accompanying tumor lysis syndrome is a serious complication in neoplasia with rapid proliferation and destruction. To confirm the efficacy of recombinant urate oxidase (rasburicase) and its safety profile, a phase IV compassionate use prospective study was performed in Korean pediatric patients with hematologic malignancies. PROCEDURE: Rasburicase was administered at 0.2 mg/kg/day once daily for 3-5 days (twice daily allowed during the first 72 hr) by intravenous route for hyperuricemia (uric acid > 7.5 mg/dl). The study period was 5 weeks and consisted of a baseline assessment within 48 hr before the administration of rasburicase, 3-5 days of assessment during treatment and a follow-up assessment at 4 weeks after its final administration. RESULTS: The uric acid endpoint (< or =7.0 mg/dl) was reached in 97.3% (36/37) of the patients and uric acid levels were significantly reduced in all patients (P < 0.001). Drug related toxicities were mild and reversible without any grade 4 or serious adverse event associated with rasburicase. CONCLUSION: This study confirms that rasburicase is a safe and effective agent for the treatment of hyperuricemia associated with hematologic malignancies in pediatric patients.

Whole-body MRI of paediatric malignant tumours: comparison with conventional oncological imaging methods.

PURPOSE: To evaluate the usefulness of whole-body (WB) MRI for detecting metastases from paediatric malignant tumours in comparison with conventional oncological imaging methods. MATERIALS AND METHODS: Using a 1.5-T system, a coronal short tau inversion recovery (STIR) sequence was obtained in all patients. In addition, sagittal fat-suppressed T2-weighted, sagittal STIR, or coronal fat-suppressed pre-contrast and post-contrast T1-weighted sequences were performed. Patients who underwent WB MRI and conventional oncological imaging within 15 days were enrolled in the study. In total, 58 bone scintigraphies, 26 iodine-123 (123I) meta-iodo-benzylguanidine (MIBG) scintigraphies, and 48 CT scans were available for comparison in 36 patients (median age 3.5 years; 21 boys, 15 girls) who underwent 82 WB MRI examinations. Skeletal and extraskeletal metastases were evaluated for a variety of tumour types. RESULTS: Concordance rate of WB MRI between two readers was 74%. In detecting metastases, WB MRI had higher sensitivity (99%) and PPV (94%) than bone scintigraphy (26 and 76%, respectively). In detecting skeletal metastases, WB MRI revealed higher sensitivity (100%) than 123I-MIBG scintigraphy (25%) and CT (10%). In contrast, WB MRI showed lower PPV in detecting skeletal and extraskeletal metastases (8 and 57%, respectively) than 123I-MIBG scintigraphy (100%), and lower sensitivity (60%) in detecting extraskeletal metastases than CT (100%). In 2 of 11 untreated patients, tumour staging was upgraded from stage 3 to 4 according to WB MRI findings. In 3 patients, WB MRI revealed early treatment responses (<1 year) of skeletal metastases. CONCLUSIONS: WB MRI can substitute for bone scintigraphy in detecting skeletal metastases of paediatric malignant tumours, and it is useful in evaluating initial tumour staging and early treatment responses. However, it still has only a complementary role in detecting extraskeletal metastases.

Autologous stem cell transplantation for the treatment of neuroblastoma in Korea.

Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.