Significance of serum total bilirubin as a prognostic factor for hemophagocytic lymphohistiocytosis in childhood / 영남의대학술지

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. Despite of proper treatment and improving treatment regimens, HLH patients still show a fatal prognosis. Therefore the evaluation of prognostic factor is important and there are many studies about hyperbilirubinemia as a prognostic factor in HLH. So we studied the prognostic value of hyperbilirubinemia in HLH children. METHODS: A retrospective analysis was performed about 33 patients who were diagnosed with HLH at Pusan National University Hospital and Yangsan Pusan University Hospital between January 2000 to December 2012. We reviewed the clinical characteristics, laboratory findings, and results of treatment to identify hyperbilirubinemia as a prognostic factor in HLH patients. RESULTS: The median age of patients at diagnosis was 32 months. Most of patients presented with fever, pale appearance, abdominal pain and jaundice. Forty-eight point five percentage of patients showed normal serum bilirubiln level ( or =2.0 mg/dL). In normal serum bilirubin group, 1 patient (6.3%) was relapsed and 1 patient (5.9%) was relapsed in hyperbilirubinemia group. In the hyperbilirubinemia group, the mortality was higher than the normal bilirubin group but, there was no statistical significance. CONCLUSION: As a prognostic factor serum bilirubin at diagnosis in HLH patients, there was no significant correlation between hyperbilirubinemia and poor outcome. But, our study has a limitation that the number of patients is too small and almost showed good prognosis.

A Case of Reticulohistiocytoma Mimicking Primary Cutaneous CD 4 Positive Small/medium T-cell Lymphoma / 임상소아혈액종양

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. A 5-month-old healthy girl visited our clinic for an enlarging nodule on the center of her right palm. The clinical differential diagnosis included xanthogranuloma and primary cutaneous CD4 positive small/medium T-cell lymphoma. Histopathology of the nodule showed abundant eosinophilic and glassy cytoplasm. The nuclei were round to oval shaped, with focal irregular nuclear membrane, and mitotic figures were absent. Immunohistochemical study determined that the cells were positive for CD68 but negative for CD1a. She was finally diagnosed with reticulohistiocytoma (solitary epithelioid histiocytoma).

A Case of Reticulohistiocytoma Mimicking Primary Cutaneous CD 4 Positive Small/medium T-cell Lymphoma / 임상소아혈액종양

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. A 5-month-old healthy girl visited our clinic for an enlarging nodule on the center of her right palm. The clinical differential diagnosis included xanthogranuloma and primary cutaneous CD4 positive small/medium T-cell lymphoma. Histopathology of the nodule showed abundant eosinophilic and glassy cytoplasm. The nuclei were round to oval shaped, with focal irregular nuclear membrane, and mitotic figures were absent. Immunohistochemical study determined that the cells were positive for CD68 but negative for CD1a. She was finally diagnosed with reticulohistiocytoma (solitary epithelioid histiocytoma).

Childhood acute lymphoblastic leukemia with hyperleukocytosis at presentation

BACKGROUND: Hyperleukocytosis caused by acute lymphoblastic leukemia (ALL) is associated with early morbidity and mortality due to hyperviscosity arising from the excessive number of leukocytes.This study was designed to assess the incidence of hyperleukocytosis, survival outcomes, and adverse features among pediatric ALL patients with hyperleukocytosis. METHODS: Between January 2001 and December 2010, 104 children with previously untreated ALL were enrolled at the Pusan National University Hospital. All of them were initially stratified based on the National Cancer Institute (NCI) risk; 48 (46.2%) were diagnosed with high-risk ALL. The medical charts of these patients were retrospectively reviewed. RESULTS: Twenty (19.2%) of the 104 children with ALL had initial leukocyte counts of >100x10(9)/L, and 11 patients had a leukocyte count of >200x10(9)/L. Male gender, T-cell phenotype, and massive splenomegaly were positively associated with hyperleukocytosis. Common early complications during induction therapy included renal dysfunction, and central nervous system hemorrhage. The complete remission (CR) rate for the pediatric ALL patients with hyperleukocytosis (94.1%) was similar to the overall CR rate (95.6%). The estimated 3-year event free survival (EFS) and overall survival of ALL children with hyperleukocytosis were 75.0% and 81.2%, respectively. However, patients with initial leukocyte counts >200x10(9)/L had a lower EFS than those with initial leukocyte counts 100-200x109/L (63.6% vs. 100%; P=0.046). CONCLUSION: The outcome of pediatric ALL cases with an initial leukocyte count >200x10(9)/L was very poor, probably due to early toxicity-related death during induction therapy.

Clinical Outcome of Relapsed or Refractory Burkitt Lymphoma and Mature B-Cell Lymphoblastic Leukemia in Children and Adolescents / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: 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. RESULTS: 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). CONCLUSION: 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.

Congenital leukemia of fetus with acquired AML1 gene duplication

Congenital leukemia is very rare, and its prevalence according to recently published papers is from 1 to 5 per million live births. This can be often diagnosed in postpartum throughout bone marrow biopsy, showing abnormal proliferation of immature blasts and granulocytic precursors. Hepatosplenomegaly is the most common feature which is found during perinatal examinations, that diagnosing is difficult during perinatal period. Hepatosplenomegaly can occur not only in congenital leukemia but in many other cases such as infection which is the most common cause. In other words, congenital leukemia is the one of the rare causes of hepatosplenomegaly. However, this case shows the fetus with the features of hepatosplenomegaly during perinatal period and being diagnosed as congenital leukemia associated with acquired AML1 gene duplication in postpartum through bone marrow biopsy. Due to its rare instance, we are to describe the case with a review of literatures.

The effectiveness of tacrolimus and minidose methotrexate in the prevention of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in children: a single-center study in Korea

BACKGROUND: Knowledge of the roles of tacrolimus and minidose methotrexate (MTX) in the prevention of acute graft-versus-host disease (aGVHD) in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) is limited. We retrospectively evaluated the engraftment status, incidence of aGVHD and chronic GVHD (cGVHD), and toxicities of tacrolimus and minidose MTX in aGVHD prophylaxis in children undergoing allogeneic HSCT. METHODS: Seventeen children, who underwent allogeneic HSCT and received tacrolimus and minidose MTX as GVHD prophylaxis from March 2003 to February 2011, were reviewed retrospectively. All the patients received tacrolimus since the day before transplantation at a dose of 0.03 mg/kg/day and MTX at a dose of 5 mg/m2 on days 1, 3, 6, and 11. RESULTS: Of the 17 patients, 9 received human leukocyte antigen (HLA)-matched related donor transplants, and 8 received HLA-matched, or partially mismatched unrelated donor transplants. The median time for follow-up was 55 months. The incidence of aGVHD in the related and unrelated donor groups was 22.2% and 42.9%, respectively. cGVHD was not observed. To maintain therapeutic blood levels of tacrolimus, the younger group ( or =8 years) (P=0.0075). The adverse events commonly associated with tacrolimus included hypomagnesemia (88%), nephrotoxicity (23%), and hyperglycemia (23%). CONCLUSION: Tacrolimus and minidose MTX were well tolerated and effective in GVHD prophylaxis in pediatric patients undergoing allogeneic HSCT. Children <8 years of age undergoing HSCT required increased doses of tacrolimus to achieve therapeutic levels.

Primary Undifferentiated Penile Sarcoma in Adolescence

We report a case of primary penile undifferentiated sarcoma. A 16-year-old adolescent man visited Pusan National University Hospital complaining of a painless mass on his penis that was increasing in size. Magnetic resonance images revealed a 5x5-cm mass and pathological examinations revealed small round cell sarcomas with neuroendocrine differentiation. The tumor, which had metastatic pulmonary nodules, was treated by tumorectomy and systemic chemotherapy. Thirty-four months after the initial diagnosis, the patient was still alive without evidence of local recurrence or metastatic disease. This is our second case of an undifferentiated penile sarcoma.

Seizures in Children Receiving Cancer Treatment / 임상소아혈액종양

BACKGROUND: The neurological complications of childhood patients with cancer are caused by brain metastasis, chemotherapy, and infection. Seizure is one of the most important neurological complications of pediatric patients receiving chemotherapy. This study was designed to identify the causes, clinical manifestations, and prognosis of seizures in children receiving cancer treatment. METHODS: We retrospectively reviewed the medical records of pediatric cancer patients with seizures at Pusan National University Hospital from January 2005 to December 2010. RESULTS: Among 271 patients, 31 experienced seizures (19 males and 12 females), and the mean age at the first seizure was 8.6 years (1.7-18.0 years). Seizures frequently occurred in patients with brain tumors (27.8%), and the types of seizures were generalized seizure in 15 patients (48.4%) and partial in 16 cases (51.6%). Eighteen (62.0%) of 29 patients who underwent a brain magnetic resonance imaging study and 21 (75.0%) of 28 cases who received an electroencephalogram recorded abnormal findings. The causes of seizures were drugs, CNS infections, and brain metastasis each in five cases (16.2%). Drugs were the most common cause in patients with a hematological malignancy (16.2%), whereas brain metastasis was the most common cause in patients with solid tumors (12.9%). Eight (40.0%) of 20 patients who survived received anticonvulsants. Eleven patients (35.5%) expired, and the most common cause of death was progression of the malignancy. CONCLUSION: Drugs, CNS infection, and brain metastasis of tumors were the most common causes of seizure in children with malignancy.

Seizures in Children Receiving Cancer Treatment / 임상소아혈액종양

BACKGROUND: The neurological complications of childhood patients with cancer are caused by brain metastasis, chemotherapy, and infection. Seizure is one of the most important neurological complications of pediatric patients receiving chemotherapy. This study was designed to identify the causes, clinical manifestations, and prognosis of seizures in children receiving cancer treatment.METHODS: We retrospectively reviewed the medical records of pediatric cancer patients with seizures at Pusan National University Hospital from January 2005 to December 2010.RESULTS: Among 271 patients, 31 experienced seizures (19 males and 12 females), and the mean age at the first seizure was 8.6 years (1.7-18.0 years). Seizures frequently occurred in patients with brain tumors (27.8%), and the types of seizures were generalized seizure in 15 patients (48.4%) and partial in 16 cases (51.6%). Eighteen (62.0%) of 29 patients who underwent a brain magnetic resonance imaging study and 21 (75.0%) of 28 cases who received an electroencephalogram recorded abnormal findings. The causes of seizures were drugs, CNS infections, and brain metastasis each in five cases (16.2%). Drugs were the most common cause in patients with a hematological malignancy (16.2%), whereas brain metastasis was the most common cause in patients with solid tumors (12.9%). Eight (40.0%) of 20 patients who survived received anticonvulsants. Eleven patients (35.5%) expired, and the most common cause of death was progression of the malignancy.CONCLUSION: Drugs, CNS infection, and brain metastasis of tumors were the most common causes of seizure in children with malignancy.

Clinical Features of Congenital Cystic Adenomatoid Malformation of the Lung / 소아알레르기및호흡기학회지

PURPOSE: Congenital cystic adenomatoid malformation (CCAM) is a rare variant of congenital pulmonary cystic disease, which is characterized by a proliferation of the dilated bronchiolar-like structure of varying size and/or distribution. In this study, we described the clinical manifestations of CCAM in a single institution during a 12-year period. METHODS: Twenty patients diagnosed with CCAM who were admitted at Busan National University Hospital between January 1995 and December 2007, were investigated for their presenting characteristics, age at diagnosis, locations, histopathologic types, combined anomalies, treatments and outcomes. RESULTS: Twenty patients diagnosed with CCAM were reviewed. Twelve males and eight females, the mean age of the patients was 7.5 years. The main symptoms were coughing, sputum, recurrent infection, chest pain, cyanosis and tachypnea. Seven patients were antenatally diagnosed and two patients were incidentally diagnosed. Radiologic findings were multiple cysts in 15 cases, solitary cyst in 2, consolidation in 3, pleural effusion in 4, tracheal deviation in 2, and abscess in 1 case. The most common location of cystic lesion was the right lower lobe, which includes 9 cases (45%). According to Stocker's histologic classification of CCAM, type I was found in 11 cases (73%), type II in 2 cases and type III in 1 case. In 5 cases, there were combined anomalies including ipsilateral pulmonary sequestration, dextrocardia, pectus excavatum, patent ductus arteriosus, accessory bronchus, and bronchogenic cyst. Fifteen patients underwent lobectomy, two patients are going to have operation and other 3 patients were transferred from regional hospital after diagnosis. All patients who underwent surgical resection improved. CONCLUSION: CCAM is a rare but potentially life-threatening pulmonary anomaly, which can be found at different ages and presents with various clinical findings. The possibility of an underlying CCAM should be considered in children with recurrent pulmonary infections or persistent abnormalities on chest X-rays following an acute infection.

Prevalence and clinical significance of the positive antinuclear antibody in children with idiopathic thrombocytopenic purpura / 소아과

PURPOSE: An association between idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE) has been recognized for decades because thrombocytopenia is the first manifestation in some patients with SLE. However, the risk of later development of SLE in childhood ITP is currently unknown. We retrospectively evaluated the incidence and clinical significance of the positive antinuclear antibody (ANA) in children with acute ITP. METHODS: This study was retrospectively performed to review the clinical and laboratory characteristics in 77 children diagnosed to have acute ITP and admitted to the Pusan National University Hospital between January 2003 and December 2006. Patients tested positive for ANA were regularly followed-up for at least 12 months for symptoms indicative of SLE. RESULTS: Seventy-seven children were included in the study; 38 males (49.4%) and 39 females (50.5%), the mean age was 4.5 years. Sixteen (20.8%) ITP patients had a positive ANA, with a median titer of 1:320. The mean age of the patients with positive ANA was 9.3 years, which is much older than 3.3 years for patients with negative ANA (P<0.05). The positive ANA group was predominantly female (81.3%) compared to the negative ANA group (P<0.05). There was no statistically significant difference in mean platelet counts between both groups. No statistically significant difference was found in ANA positivity and progression to chronic ITP or SLE. After the median follow-up of 32 months, SLE was diagnosed only in one ITP patient with positive ANA. CONCLUSION: Our data demonstrated that ANA positivity is often found in children with acute ITP. Large-scale studies should be considered to determine the significance of ANA positivity in childhood ITP for the later development of SLE.