Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days –8 to –5), and the target area under the curve was 75,000 µg·hr/L. Fludarabine (40 mg/m2) was administered once daily for 6 consecutive days from days –8 to –3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days –4 to –2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.
Chronic granulomatous disease; Bone marrow transplantation; Transplantation conditioning; Busulfan; Fludarabine
Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that affects young children. Due to its extreme rarity, most of the available data are based on retrospective case series. To add to the current knowledge of this disease, we reviewed the patients treated for extra-cranial MRT in our institute.
Materials and Methods
A retrospective medical record review was conducted on children treated for pathologically confirmed extra-cranial MRT at Seoul National University Children’s Hospital between January 2003 and May 2013.
Eleven patients (7 boys, 4 girls) were diagnosed with extra-cranial MRT at a median age of 9 months old. INI1 staining was important in the pathological confirmation. Six patients (55%) had renal MRT and five (45%) had soft tissue MRT. Five patients (45%) had metastases at diagnosis. All patients underwent chemotherapy, eight patients (73%) underwent surgery, six patients (55%) received therapeutic radiotherapy, and four patients (36%) underwent high dose chemotherapy with autologous stem cell rescue (HDCT/ASCR) with melphalan, etoposide, and carboplatin. Five patients (45%) died of disease following progression (n=3) or relapse (n=2), however, there was no treatment related mortality. The overall survival of the cohort was 53.0% and the event-free survival was 54.5% with a median follow-up duration of 17.8 months (range, 2.3 to 112.3 months).
Extra-cranial MRT is still a highly aggressive tumor in young children. However, the improved survival of our cohort is promising and HDCT/ASCR with melphalan, etoposide, and carboplatin may be a promising treatment option.
Rhabdoid tumor; Kidney neoplasms; Soft tissue neoplasms; Neoplasm metastasis
Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, splenomegaly, jaundice, and pathologic findings of hemophagocytosis in bone marrow or other tissues such as the lymph nodes and liver. Pleocytosis, or the presence of elevated protein levels in cerebrospinal fluid, could be helpful in diagnosing HLH. However, the pathologic diagnosis of the brain is not included in the diagnostic criteria for this condition. In the present report, we describe the case of a patient diagnosed with HLH, in whom the brain pathology, but not the bone marrow pathology, showed hemophagocytosis. As the diagnosis of HLH is difficult in many cases, a high level of suspicion is required. Moreover, the pathologic diagnosis of organs other than the bone marrow, liver, and lymph nodes may be a useful alternative.
Hemophagocytic lymphohistiocytosis; Central nervous system; Brain
Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered.
Pediatrics; Neoplasms; Survival rate; Leukemia; Brain neoplasms
Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV) itraconazole to be associated with serious cases of blood pressure (BP) drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug.
Materials and methods
We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP) measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥20%) drops.
Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0–160.33 mmHg] versus 105 [59.8–148.3 mmHg]; P<0.001). The decrease in SBP was associated with the application of continuous renal replacement therapy (CRRT) (P=0.012) and the use of inotropic (P=0.005) and hypotensive drugs (P=0.021). A clinically meaningful SBP drop was seen in 5.37% (141 out of 2,627) of the administrations, and the use of inotropics (odds ratio [OR] 6.70, 95% confidence interval [CI] 3.22–13.92; P<0.001), reducing the dose of inotropics (OR 8.08; 95% CI 1.39–46.94; P=0.02), CRRT (OR 3.10, 95% CI 1.41–6.81; P=0.005), and bacteremia (OR 2.70, 95% CI 1.32–5.51; P=0.007) were risk factors, while age was a protective factor (OR 0.93, 95% CI 0.89–0.97; P<0.001).
A decrease in SBP was associated with IV administration of itraconazole. It was particularly significant in younger patients with bacteremia using inotropic agents and during application of CRRT. Careful attention to hypotension is warranted during IV administration of itraconazole in this group of patients.
itraconazole; blood pressure; hemato-oncologic disease; hypotensive drug; inotropics; CRRT
An epidemiologic study of childhood cancer would provide useful information on cancer etiology and development of management guidelines.
Materials and Methods
Data from the Korea National Cancer Incidence Database were used to examine the incidence and survival of cancer in patients aged 0-14 years. Patients were grouped according to the International Classification of Childhood Cancer, 3rd edition. Age-specific and age-standardized incidences per million and estimated annual percentage change (APC) were calculated by sex and age. Five-year relative survival was calculated for four periods from 1993 to 2011.
The study comprised 15,113 patients with malignant neoplasms. Age-standardized incidence rates for all cancers were 134.9 per million children in 1999-2011 and 144.0 and 124.9 per million for males and females, respectively (M/F ratio, 1.2; p < 0.05). The highest incidences were observed for ‘leukemias, myeloproliferative diseases, and myelodysplastic diseases’ (group I) (46.4), ‘central nervous system neoplasms’ (group III) (18.3), and ‘lymphomas and reticuloendothelial neoplasms’ (group II) (13.4). Age-standardized incidence increased from 117.9 in 1999 to 155.3 in 2011, with an APC of 2.4% (95% confidence interval, 2.1 to 2.7). There was a significant increase of APC in ‘neuroblastoma and other peripheral nervous cell tumors’ (group IV) (5.6%) and ‘other malignant epithelial neoplasms and malignant melanomas’ (group XI) (5.6%). The 5-year relative survival rate for all childhood cancers improved significantly from 56.2% (1993-1995) to 78.2% (2007-2011) (males, 56.7% to 77.7%; females, 55.5% to 78.8%).
This study provides reliable information on incidence and survival trends for childhood cancer in Korea.
Neoplasms; Child; Incidence; Survival; Korea
AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy.
METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD.
RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy.
CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group.
Hematopoietic stem cell transplantation; Veno-occlusive disease; Cyclosporine; Adverse drug reaction; Total bilirubin
The neurocognitive function and quality of life of 58 Korean survivors of childhood medulloblastoma were assessed after surgery, cranial radiation and chemotherapy. All patients were evaluated with a battery of neurocognitive function tests and the Pediatric Functional Assessment of Cancer Therapy-Brain Tumor Survivors, which consists of self-report questionnaires on quality of life. The mean full-scale intelligence quotient (IQ), verbal IQ, and performance IQ scores were 90.2, 97.1, and 84.16, respectively. The mean memory quotient (MQ) score was 86.78, which was within 1 standard deviation of the average score of 100. Processing speed, attention, and executive function showed mild to moderate deficits. Intelligence, memory, executive function, visuospatial function, and simple motor function were significantly lower in the patients diagnosed before 8 years of age compared with those diagnosed after 8. The cognitive deficits in the patients diagnosed at younger ages might be related to earlier exposure to craniospinal irradiation and chemotherapy. The patient and parent proxy evaluations of attention, fine motor function, and quality of life did not differ. We found significant neurocognitive changes in a wide range of neurocognitive functional domains in Korean survivors of childhood medulloblastoma. Long-term follow-up studies of survivors of childhood medulloblastoma beginning at the time of their first diagnosis are required to better understand the deficits exhibited by survivors of childhood medulloblastoma, so that intervention strategies and treatment refinements that reduce the long-term neurocognitive decline can be developed.
Medulloblastoma; Survivors; Cognition; Quality of Life; Korea
To evaluate the association between coronary artery calcium (CAC) and cortical thickness in a large sample of cognitively normal individuals, with special emphasis in determining if the association thickness has regional brain specificity and if it is mediated by white matter hyperintensities (WMH). A total of 512 participants were included in this study. CAC scores were assessed by multi-detector computed tomography. Cortical thickness was measured using a surface-based method. Linear mixed models were used to assess the association between CAC scores and cortical thickness. In fully adjusted models, increased CAC scores were associated with cortical thinning across several brain regions, which generally overlapped with the distribution of default mode network. The association between CAC scores and cortical thickness was significantly stronger in participants with moderate or severe WMH compared to those with none or mild WMH, even though CAC scores were not associated with WMH. In cognitively normal adults, CAC was associated with cortical thinning in areas related to cognitive function. This association was evident after adjusting for multiple coronary artery disease risk factors and for WMH, suggesting that CAC may be more closely related to Alzheimer’s Disease-type disease rather than to cerebral small vessel disease.
Prompt treatment affects prognosis and survival after acute myocardial infarction (AMI) onset. This study evaluated the awareness of early symptoms of AMI and knowledge of appropriate responses on symptom occurrence, along with related factors.
Participants’ knowledge of the early symptoms of and responses to AMI onset were investigated using a random digit dialing survey. We included 9600 residents of 16 metropolitan cities and provinces in Korea.
The proportions of respondents who were aware of early symptoms of AMI ranged from 32.9% (arm or shoulder pain) to 79.1% (chest pain and discomfort). Of the respondents, 67.0% would call an ambulance if someone showed signs of AMI, 88.7% knew ≥1 symptom, 10.9% knew all five symptoms, and 3.1% had excellent knowledge (correct identification of all five AMI symptoms, not answering “Yes” to the trap question, and correctly identifying calling an ambulance as the appropriate response when someone is exhibiting AMI symptoms). The odds ratio (OR) for having excellent knowledge was significantly higher for those who graduated college or higher (OR 3.42; 95% confidence interval [CI], 1.09–10.76) than for those with less than a primary school education, as well as for subjects with AMI advertisement exposure (OR 1.49; 95% CI, 1.10–2.02) and with knowledge of AMI (OR 1.63; 95% CI, 1.16–2.27). The 60- to 79-year-old group had significantly lower OR for excellent knowledge than the 20- to 39-year-old group (OR 0.53; 95% CI, 0.28–0.99).
Awareness of AMI symptoms and the appropriate action to take after symptom onset in South Korea was poor. Therefore, educational and promotional strategies to increase the overall awareness in the general public, especially in the elderly and those with low education levels, are needed.
public; awareness; acute myocardial infarction; early symptoms; telephone survey
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.
Quality of Life; Questionnaires; Validation Studies; Child Psychology; Neoplasms; Survivors
Few literatures have elaborated on the clinical characteristics of children with thalassemia from low-prevalence areas. A retrospective analysis was conducted on children genetically confirmed with thalassemia at Seoul National University Children's Hospital in Korea. Nine children (1α thalassemia trait, 6β thalassemia minor, 2β thalassemia intermedia) were diagnosed with thalassemia at median age of 4.3 yr old with median hemoglobin of 9.7 g/dL. Seven (78%) children were incidentally found to be anemic and only 2 with β thalassemia intermedia had presenting symptoms. Five children (56%) were initially misdiagnosed with iron deficiency anemia. Despite the comorbidities due to α thalassemia mental retardation syndrome, the child with α thalassemia trait had mild hematologic profile. Children with β thalassemia intermedia had the worst phenotypes due to dominantly inherited mutations. None of the children was transfusion dependent and most of them had no complications associated with thalassemia. Only 1 child (11%) with codon 60 (T→A) mutation of the HBB gene needed red blood cell transfusions. He also had splenomegaly, cholelithiasis, and calvarial vault thickening. Pediatricians in Korea must acknowledge thalassemia as a possible diagnosis in children with microcytic hypochromic hemolytic anemia. High level of suspicion will allow timely diagnosis and managements.
α-Thalassemia; β-Thalassemia; Genotype; Phenotype; Child; Korea
The aim of our study was to establish a safe and convenient diagnostic method for acute gastrointestinal (GI) graft-versus-host disease (GVHD) in children by determining the sensitivity and negative predictive values of upper and lower endoscopic biopsies for children suspected of GI GVHD.
Patients suspected of GI GVHD who received endoscopic evaluation within 100 days after stem cell transplantation and endoscopies between January 2012 and March 2014 in Seoul National University Children's Hospital were included in our study.
Fifteen patients with a total of 20 endoscopic procedures were included in our study. Sensitivity at the esophagus, stomach, and duodenum were 22.2%, 30.0%, and 80.0%, respectively. Negative predictive values at the esophagus, stomach, and duodenum were 22.2%, 30.0%, and 60.0%, respectively. Overall sensitivity and negative predictive values of upper endoscopic biopsy for GVHD were 77.8% and 50.0%, respectively. Overall sensitivity and negative predictive values of lower endoscopic biopsy for GVHD were 88.9% and 66.7%, respectively.
We recommend flexible sigmoidoscopy as a safe and accurate diagnostic tool for GVHD, similar to other studies reported previously. However, if there is no evidence of GVHD on sigmoidoscopy with high index of suspicion of GI bleeding, full colonoscopy and upper endoscopy should be considered.
Graft-versus-host disease; Child; Endoscopy
Primary CNS lymphoma (PCNSL) is a very uncommon disease in children, and usually treated by chemotherapy, combined with focal or craniospinal radiotherapy (RT). However, adverse effects of RT are a concern. We evaluated the outcomes of childhood PCNSL, treated with systemic and intrathecal chemotherapy, but without RT. For fifteen years, six patients among 175 of non-Hodgkin lymphoma were diagnosed as PCNSL in Seoul National University Children's Hospital and we analyzed their medical records retrospectively. Their male:female ratio was 5:1, and median age was 10.1 yr. The primary sites were the sellar area in three patients, parietal area in one, cerebellum in one, and multiple areas in one. Their pathologic diagnoses were diffuse large B-cell lymphoma in three patients, Burkitt lymphoma in two, and undifferentiated B-cell lymphoma in one. Five were treated with the LMB96 treatment protocol, and one was treated with the CCG-106B protocol. None had RT as a first-line treatment. One patient had a local relapse and received RT and salvage chemotherapy, without success. No patient had treatment-related mortality. Their estimated 5-yr event-free and overall survival rates were both 83.3%. In conclusion, PCNSL is a rare disease in childhood, but successfully treated by chemotherapy without RT.
Primary CNS Lymphoma; Children; Irradiation
We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures.
Chronic graft versus host disease (GVHD) is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT), but simultaneous small bowel obstruction is rare. Here, we report a child with acute myeloid leukemia who received an allogeneic HSCT from an unrelated matched donor. After HSCT, the patient developed severe chronic GVHD involving the small intestine, leading to obstruction of the terminal ileum. Small bowel resection was performed, and the symptoms improved without severe complications. Bowel obstruction should be considered as a possible complication of chronic GVHD; surgery may be a valuable corrective measure.
Acute myeloid leukemia; Hematopoietic stem cell transplantation; Graft versus host disease; Intestinal obstruction
Retinoblastoma is the most common intraocular malignancy in children. Since the 1990s, chemotherapy was indicated for intraocluar disease to reduce the frequency of enucleation and spare the complications associated with external beam radiation. In this study, we analyzed treatment results of retinoblastoma in our institute.
Materials and Methods
Datas from children diagnosed with retinoblastoma and treated at Seoul National University Children's Hospital between 1986 and 2008 were analyzed retrospectively. We utilized cyclophosphamide, vincristine, adriamycin, and methotrexate (CVAM) for OPD-based adjuvant chemotherapy. From 1990, primary chemotherapy was administered to patients with intraocular disease for eyeball-saving and patients received a combination of etoposide, vincristine, cisplatin (or ifosfamide) as a moderately intensive regimen, or a combination of cisplatin, doxorubicin, etoposide, and cycophosphamide (CDEC) as a highly intensive regimen.
One hundred eighteen children were analyzed. There were 68 unilateral and 50 bilateral diseases. The median age at diagnosis was 1 year and Reese-Ellsworth stage V was the most common stage at the time of diagnosis. All patients were treated by chemotherapy-based multimodality methods, and primary chemotherapy was administered to 80 patients. The 10-year overall and event-free survival rate of all patients were 93.9% and 91.6%, respectively. Two patients who died were in the CDEC regimen group, but there was no significant statistical difference in survival rates by chemotherapy regimens. Fifty-six of 114 eyeballs were saved after primary chemotherapy-based treatment, and the eyeball-saving rate was 49.1%. Six patients relapsed after enucleation and 2 patients were treated successfully after autologous PBSCT. Osteosarcoma occurred in 2 patients as a secondary malignancy, and facial asymmetry after radiotherapy was the most common long-term sequelae.
In this study, the overall and event-free survival rates of retinoblastoma were satisfactory and eye-saving was possible with primary chemotherapy. Development of new chemotherapeutic regimens and a team approach are necessary to improve the eyeball-saving rate.
Retinoblastoma; Chemotherapy; Radiotherapy; Enucleation; Survival rate; Eyeball-saving
In this study, we investigated the clinical characteristics and treatment results of osteosarcoma during the past 7 years, and evaluated the role of high dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT).
Materials and Methods
We retrospectively analyzed the clinical data of patients who were diagnosed as osteosarcoma at our center from January, 2000 to December, 2007.
The 5-year overall survival and event-free survival of the patients were 72.6% and 55.9%, respectively. Seventeen (41.5%) patients showed disease progression during treatment or relapse after the end of treatment. The patients who had metastasis at diagnosis or who had a lower grade of necrosis after neoadjuvant chemotherapy showed decreased overall and event-free survival. Four patients received ASCT after HDCT, and 3 of them are alive without disease.
The patients who relapsed or had refractory osteosarcoma or who had metastasis at diagnosis or a lower grade of necrosis after neoadjuvant chemotherapy showed poor prognosis. HDCT with ASCT could be an alternative treatment option for these patients.
Osteosarcoma; Autologous stem cell transplantation; High dose chemotherapy; Pediatrics
Following the introduction of a multimodal approach to diagnosis and treatment, the prognosis of rhabdomyosarcoma (RMS) has markedly improved over the last three decades. However, there are few data on treatment outcomes in Korean patients.
Materials and Methods
We performed a retrospective analysis of 77 patients with RMS diagnosed and treated at Seoul National University Children's Hospital between 1986 and 2005.
The overall 5-year survival and event-free survival rates for all patients were 77% and 59%, respectively. The Intergroup Rhabdomyosarcoma Study clinical grouping and initial response to treatment (20-week response) were important prognostic factors.
The outcome of childhood RMS was closely associated with the initial staging and the initial response to treatment. Modulating therapies according to initial responses and risk factors is critical, and new treatment strategies for high-risk patients are needed.
Rhabdomyosarcoma; Prognosis; Korea; Child
In response to the challenges and difficulties imposed by rare cancers, multi-stakeholder initiatives dedicated to improving rare cancer care was launched, and several recommendations were made by professional societies. However, these primarily reflect the view of the advocates and supporters, and may not represent the views of the “average” clinician or researcher. In this study, we sought to investigate perceived difficulties with regard to rare cancer care and potential solutions endorsed by oncologists.
Materials and Methods
A representative sample of 420 oncologists recruited in 13 cancer centers participated in a nationwide survey.
Oncologists faced various difficulties in treatment of patients with rare cancers, including the lack of clinical practice guidelines (65.7%) and personal experience (65.2%), lack of approved treatment options (39.8%), and reimbursement issues (44.5%). They were generally supportive of recent recommendations by multi-stakeholder initiatives as well as professional societies for development of clear clinical practice guidelines (66.0%), flexible reimbursement guidelines (52.9%), and a national rare cancer registry (47.4%). However, there was only moderate endorsement for referrals to high-volume centers (35.5%) and encouragement of off-label treatments (21.0%).
Insights into the general attitudes of oncologists gained through our nationwide survey of representative samples would be helpful in development of clinical practices and public health policies in rare cancer treatment and research.
Rare diseases; Cancer; Oncologists; Attitude; Recommendation
The survival in cases with relapsed Wilms tumor is dismal. Recently, however the introduction of new therapeutic agents and experimental strategies has improved the survival. We analysed the survival of patients with relapsed Wilms tumor according to the treatment period. During the early period 1983-1993, patients who had received two drugs were treated with doxorubicin and the others were treated with cisplatin and etoposide, whereas during the late period 1994-2004, patients were treated with combinations of cyclophosphamide/etoposide and carboplatin/etoposide. During the early period, 8 of 57 experienced relapse, and 8 of 41 relapsed during the late period. Only 2 patients treated during the early period survived in complete response (CR), whereas during the late period, 5 patients remained alive in CR, and 3 of those received high-dose chemotherapy (HDC) with autologous peripheral stem cell rescue (SCR). The estimated 5 yr event-free survival rate was 37.5% in the entire study group, 50% for patients in the late period, and 25% for patients in the early period (p=0.38). The survival in patients with relapsed Wilms tumor dramatically improved during the late period and HDC with SCR was one of the effective salvage strategies.
Wilms Tumor; Nephroblastoma; Recurrence; Salvage Therapy; Stem Cells
Despite the rapid improvement in survival rate from Burkitt lymphoma and mature B-cell lymphoblastic leukemia (B-ALL) in children, a small subset of patients do not respond to first-line chemotherapy or experience relapse (RL). Herein, we report the clinical characteristics and outcomes of these patients.
Materials and Methods
RL or refractory Burkitt lymphoma and mature B-ALL in 125 patients diagnosed from 1990 to 2009 were retrospectively analyzed.
Nineteen patients experienced RL or progressive disease (PD). Among them, 12 patients had PD or RL less than six months after initial treatment and seven had late RL. Seven patients achieved complete response (CR), 11 had PD, and one had no more therapy. Six patients who achieved CR survived without evidence of disease and four of them underwent high-dose chemotherapy (HDC) followed by stem cell transplantation (SCT). However, 11 patients who failed to obtain CR eventually died of their disease. Five-year overall survival (OS) was 31.6±10.7%. OS of patients with late RL was superior to that of patients with early RL (57.1±18.7%, vs. 16.7±10.8%, p=0.014). Achievement of CR after reinduction had significant OS (p < 0.001). OS for patients who were transplanted was superior (p < 0.01). In multivariate analysis, achievement of CR after reinduction chemotherapy showed an association with improved OS (p=0.05).
Late RL and chemotherapy-sensitive patients have the chance to achieve continuous CR using HDC/SCT, whereas patients who are refractory to retrieval therapy have poor prognosis. Therefore, novel salvage strategy is required for improvement of survival for this small set of patients.
Burkitt lymphoma; Recurrence; Children
Patients with autoimmune disorders often have low levels of 25-hydroxyvitamin D [25(OH)D3], which correlates with disability or disease activity. Vitamin D may play a role in neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD), as an important factor involved in immunological pathways. We investigated the relationship between vitamin D levels and disease related disability and clinical activity in patients with NMOSD. Blood samples from 51 patients with NMOSD who were positive for anti-aquaporin4-antibody (AQP4-ab) and 204 healthy controls were collected for 25(OH)D3 measurement. Clinical parameters, including expanded disability status scale (EDSS) score, annualized relapse rate (ARR) and time of blood sampling relative to attack, were determined in patients with NMOSD. We found that 25(OH)D3 levels were significantly lower in patients with NMOSD compared to healthy controls. There was no difference between 25(OH)D3 levels in blood samples taken at relapse or remission, and no association between 25(OH)D3 levels and ARR, but there was an inverse correlation between 25(OH)D3 levels and EDSS scores in patients with NMOSD. It remains to be determined whether low vitamin D levels predispose to NMO and/or modify disease severity, or are secondary to neurological disability. In either case the results could also be of relevance to other neurological diseases such as multiple sclerosis as well as NMO.
There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (n = 73) were compared to those of the doxycycline-treated group (n = 108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [P > 0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (P > 0.05). In complicated scrub typhus patients (n = 181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56; P < 0.001). Our data suggest that outcomes of azithromycin therapy are comparable to those of doxycycline therapy in patients with complicated scrub typhus.