Analgesic Effect of Oral Glucose and Pacifiers in Term Neonates during Minor Procedures

PURPOSE: Newborns may undergo many kinds of minor procedures. Since painful events during procedures may cause adverse effects on growth and/or development, nonpharmacological way to relive pain have been extensively studied including oral glucose and pacifiers. This study was undertaken to evaluate the analgesic effects of orally administered glucose and pacifiers in term neonates during minor procedures using validated behavioral pain rating system. METHODS: Randomized prospective studies with 81 term infants were assigned to one of three treatment groups: placebo (2 ml sterile water), glucose (2 ml 30% glucose), and pacifier (2 ml 30% glucose followed by a pacifier) during heelsticks. Intensity of pain was assessed by Douleur Aigue Nouveau-ne scale (DAN scale). RESULTS: Median pain scores (interquartile) during minor procedure and after 30 seconds were 7 (6-10), 4 (3-8) for sterile water; 7 (3-8), 1 (0-5) for 30% glucose; 4 (2-6), 1 (0-1) for 30% glucose and pacifiers, respectively. P values for comparisons of sterile water versus 30% glucose, and 30% glucose versus 30% glucose plus pacifiers were 0.019, 0.035 for during the procedure and 0.006, 0.034 for after 30 seconds, respectively. CONCLUSION: The analgesic effect of oral glucose during minor procedure is clinically apparent in full term neonates. Pacifiers plus glucose have a synergetic analgesic effect in neonates. These simple and safe interventions should be widely used during minor procedures in term neonates.

Epidemiology and Clinical Characteristics of Childhood Acute Lymphoblastic Leukemia in Korea / 대한소아혈액종양학회지

PURPOSE: Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of all cases of childhood leukemia. We investigated epidemiology, clinical and laboratory features and treatment outcome of the children with ALL in Korea during recent 5 years. METHODS: One thousand forty nine patients were enrolled between January 1994 and December 1998 from 37 major hospitals in Korea. The data regarding the clinical and laboratory features including age, WBC counts at diagnosis, immunophenotype, morphology, cytogenetics and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed. The differences between groups analyzed by log-rank test. RESULTS: There were 597 males and 452 females. The distribution between the age 2 and 5 years is most common in 46.1%. The annual incidence rate per 100,000 population varied from 1.6 to 2.2. The 5 year event free survival (EFS) rates according to good prognostic factors were as follows: 67% bet ween 1-9 year of age at diagnosis, 69% in under 10,000/mm3of initial WBC count, 74% in early pre-B cell CALLA ( ) immunophenotype, 65% in L3 morphology, 68% in no CNS invasion. Most of patients were treated by CCG treatment protocol. The 5 year EFS was 63%. Main complications were sepsis (21.8%) and hemorrhage (12.5%). The relapse rate was 15.6%. The common causes of death were sepsis, DIC, pneumonia, relapse. CONCLUSION: Our results could provide the most recent and important information about acute lymphoblastic leukemia of children in Korea.

Clinical Features and Long-term Outcomes of Infant Leukemias: A Review of Ten-Years' Experiences / 대한소아혈액종양학회지

PURPOSE: Infant leukemia is rare and accounts for 5% of leukemia in children. It differs from childhood leukemia in biologic and clinical features and has a poor prognosis. Research on infant leukemia is difficult due to the scarcity of cases. We studied the clinical progress and prognosis of infant leukemia diagnosed in our hospital, in order to contribute to the treatment and prognosis of infant leukemia. METHODS: The patients who were diagnosed with leukemia in the first 12 months of life were analysed between January 1991 and December 2000 in Yonsei Medical Center. We analysed the sex, age, clinical features, treatment outcome, prognostic factor, and survival rate. RESULTS: Among a total of 41 cases, 19 cases were diagnosed with acute lymphoblastic leukemia (ALL), 15 cases with acute myelogenous leukemia (AML), 2 cases with chronic myelogenous leukemia (CML), and 5 cases were unclassifed. Twenty-two were males and 19 females; age at diagnosis was 4 months in ALL, 8 months in AML, and 4 months in CML. Common clinical features at diagnosis were pale appearance and fever, others were poor oral intake, abdominal distension, and irritability. Hyperleukocytosis with average over 20,000/mm3, anemia, and thrombocytopenia were seen. By immunologic surface marker analysis, 8 of 15 B-lineage ALL were CALLA negative, early pre-B ALL. The remission induction rate was 79% in ALL and 60% in AML. The 5 year-survival rate of 41 patients was 29.2%. Sex, age at diagnosis, white blood cell count > 50 109/L, hepatomegaly, and CNS involvement were not prognostic factors. CONCLUSION: Infant leukemia differs from childhood leukemia in biological and clinical features and has a poor prognosis. Therefore, further clinical research is needed to improve the outcome of infant leukemia.

The Clinical Features and Prognosis of Leukemia in Down Syndrome / 대한소아혈액종양학회지

PURPOSE: There are several reports that the risk of development of leukemias is much higher in Down syndrome (DS) children than in non DS children. But there are a few reports about the clinical features of leukemia in Down syndrome and the prognosis in Korea. The object of this study is to evaluate clinical features, treatment results and the prognosis of leukemia of Down syndrome patients. METHODS: We conducted retrospective reviews in 10 children with leukemia of Down syndrome who were admitted to the Department of Pediatrics in Yonsei University Hospital between March 1986 and December 2000. We analyzed the clinical features, laboratory findings and survival rates. RESULTS: A male to female ratio was 1:1.25. Median age at diagnosis was 2 years 8 months. Initial symptoms were hepatosplenomegaly, petechiae, fever and upper respiratory infection symptoms. The number of patients by the type was as followed:acute myeloid leukemia (AML) 7 (70%), acute lymphocytic leukemia 2 (20%), acute mixed lineage leukemia 1 (10%). There were 4 cases of M7 subtype in AML. The median peripheral blood cell counts were as followed; leukocyte was 41,000/muL, hemoglobin was 8.7 g/dL, the platelet was 103,000/muL. The five years event free survival rate after diagnosis was 87.5% (7/8). The one patient relapsed and another one patient died of cardiac anomaly. CONCLUSION: There seemed to be several differences of clinical features between DS leukemia and non DS leukemia, especially prognosis. Multi-centered well organized study should be done to confirm our observation.

Therapeutic Outcomes of Langerhans' Cell Histiocytosis / 대한혈액학회지

BACKGROUND: Langerhans' cell histiocytosis is a proliferative histiocytic disorder of unknown cause formerly referred to histiocytosis X, with pathologic characteristics of abnormal proliferation of histiocytes which belong to the mononuclear phagocytes. The clinical manifestations range in severity from solitary lytic bone lesions to fatal multisystem disease, typically with indolent clinical courses. The authors reported here, the clinical features and therapeutic outcomes of Langerhans' cell histiocytosis according to stage and prognostic features. METHODS: We reviewed the medical records of 38 cases with Langerhans' cell histiocytosis confirmed by biopsy from March 1983 to March 1998 in Severance hospital for disease course, treatment, and late sequelae. RESULTS: 1) Median age of the patients was 3 years-old, and the male to female ratio was 2.2:1. 2) Fifteen cases were less than 2 years of age, 21 had soft tissue involvements, 10 had more than 4 organ involvement, and 8 had involved organ dysfunction. 3) As for the clinical stages, 19 cases were in stage I, 9 in stage II, 4 in stage III, and 6 in stage IV. As for the pathologic stages, 15 had monostic disease, 2 had polyostic disease, and 21 had multisytemic disease. 4) The incidence of more than 4 organ involvement in cases or = 2 years [53.3% (8/15) vs 8.7% (2/23), P=0.004], and the incidence of organ dysfunction in cases or = 2 years [33.3% (5/15) vs 3% (3/23)], indicating that cases or = 15 years. There was a significant correlation between the presence of more than 4 organ involvement and organ dysfunction (P=0.041). 5) The response rate of all cases was 71% (27 cases), and the response rate of 25 cases who received chemotherapy was 60% (15 cases). There was no difference in the response rate according to the type of chemotherapy. Overall survival rate was 63.4% at 50 months, disease-free survival rate was 56.7% at 24 months. The disease free survival rate was significantly lower in cases younger than 2 years of age than cases older than 2 years of age (P=0.047), in cases with 4 or more organs involvement than 3 or less (P=0.0002), in cases with evidence of organ dysfunction than without evidence of organ dysfunction (P=0.082), and in cases with soft tissue involvement than with only bone involvement (P=0.043). There was significant differences in disease free survival rate according to clinical stage (P=0.001). The overall survival and disease free survival rate of the cases older than 15 years of age were similar to those of the cases younger than 15 years of age were similar to those of the cases younger than 15 years of age. 6) Five cases died during follow-up periods, organ involvement, and organ dysfunction were found to be important prognostic factors, and cases with lesions limited to skeletal system showed more than 90% of survival rate. In the future, clinical investigation enrolled with more cases about the difference of clinical features and therapeutic outcomes between adult patients and pediatric patients should be warranted.

The Clinical Outcome of Protocol R-11 Chemotherapy in Patients with Late Relapse of Childhood Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

PURPOSE: This study is to see chemotherapeutic results followed by Rotational Combination Chemotherapy (R-11 protocol) treatment for the patients with late relapse of childhood ALL six months after the completion of chemotherapy. METHODS: The subjects of study were the 13 children who had been diagnosed as ALL at the Severance Hospital and the Wonju Christian Hospital and completed the chemotherapy. They, however, diagnosed a late relapse of ALL between December, 1996 and December, 2001. After that, they were given an chemotherapy with R-11 protocol. RESULTS: The average age of the 13 patients was 11.8 ( 2.8) years old at relapse. They showed the complete remission (8 patients, 61%), partial remission (4, 31%), and induction failure (1, 8%). The total remission ratio was 92%. Four year Event Free Survival (EFS) after the second remission was 61.5%. They also showed acute toxicity during remission induction with severe than grade III according to the WHO criteria. The leukopenia and thrombocytopenia (hematologic toxicity) were seen at 11 cases (84%) and 9 cases (69%) respectively, and hepatotoxicity (non-hematologic toxicity) was shown at 6 cases (46%). There are also chronic toxicity, one case developed leukomalacia, and 6 cases did various symptoms of infections. CONCLUSION: There is no optimal chemotherapeutic protocol for late relapse of childhood ALL, and the treatment with R-11 protocol is worth a trial.

Chromosomal Analysis in Childhood Leukemia / 대한소아혈액종양학회지

PURPOSE: Chromosomal analysis has been helpful not only in pathophysiology of leukemia, but diagnosis, classification, management and predicting prognosis. However, little has been studied on chromosomal abnormality of pediatric leukemia in Korea. We have performed chromosomal analysis on childhood leukemia that we experienced, and tried to correlate chromosomal abnormalities with various types of leukemia. METHODS: Subjects were 28 of 84 patients diagnosed with leukemia and have been discovered to have chromosomal abnormalities on chromosomal analysis employing G-banding technique in Yonsei medical center from July 1996 to February 1999. RESULTS: Of the total 84 patients, Acute lymphocytic leukemia (ALL) accounted for 51 cases (61%), Acute myelocytic leukemia (AML), 30 cases (35%), Chronic myeloid leukemia (CML), 3 cases (4%). Chromosomal analysis in ALL: Of 51 cases, 9 cases (18%) showed chromosomal abnormality. Their mean age at diagnosis was 5.6+/-5.1 years. One case (12%) exhibited hyperploid (> 50 chromosomes), 4 cases (44%) pseudodiploid, and marginally-hyperdiploid was seen in 4 cases (44%). Structural abnormality involving translocation was seen in 6 cases, where t(3;9), t(4;11), t(12;?) 1 case respectively, del (13) 2 cases, and I (q9) 1 case. Chromosomal abnormality in AML: Of total 29 cases, 17 cases (55%) were found to have chromosomal abnormalities, with their mean age ranging 7.6+/-6.4 years. t(8;21) was found to be the largest, accounting for 5 cases, and t(15;17), t(1;22), t(1;11), t(10;11), del(5), inv(9) 1 case respectively, 21 trisomy in 1 case, 11 trisomy in 1 case. Other complex chromosomal abnormality was seen in 2 cases. Upon analysis of relationship between the chromosomal abnormality and FAB subtypes, 4 cases of M2- subtype were found amongst 5 cases of t(8;21), but the other chromosomal abnormalities and subtypes failed to show any correlation. Chromosomal abnormality in CML: Two cases (67%) of chromosomal abnormalities were found in 3 with CML. Their mean age at diagnosis was 152.7 years, and all cases showed t(9;22). CONCLUSION: Our study found that in pediatric AML, t(8;21) showed high incidence and was found to be related with M2-subtype. In CML, t(9;22) was found to be frequent, but the data lacks in accuracy as our sample was too small. For more precise information on incidences of chromosomal abnormalities and the prognostic implications that the cytogenetic properties of leukemia, further studies seem to be essential.

A Case of Malignant Extrarenal Rhabdoid Tumor of the Retroperitoneum / 대한소아혈액종양학회지

Malignant rhabdoid tumor is a clinically aggressive neoplasm that was initially described as a distinctive renal tumor of childhood. But among the malignant rhabdoid tumors, extrarenal rhabdoid tumor is rare. We report an extrarenal neoplasm histologically and ultrastructurally identical to renal rhabdoid tumor that arose in the retroperitoneum of a 4-month-old boy and presented as a right lower abdominal mass. The tumor had an aggressive clinical course despite multimodal therapeutic regimens, and the patient died with disseminated disease 12 months after diagnosis.

Mutational Analysis of CDKN2 (p16-INK4A/MTS1) Gene in Childhood Acute Leukemia / 대한소아혈액종양학회지

PURPOSE: The human chromosome 9p21 region that is a frequent site of deletions and rearrangements in many tumor types including leukemias implied the existence of a tumor suppressor gene within 9p21 which is involved in tumor formation. CDKN2 (p16) gene is located in the same chromosomal region. The loss of CDKN2 function is probably one of the most common genetic alterations and is now thought to play a key role in leukemogenesis. We examined the frequency of the point mutation of CDKN2 gene by analyzing the DNA sequence and demonstrated the prognostic implication of mutations of CDKN2 gene in childhood acute leukemia. METHODS: We investigated the prevalence of the point mutation in thirty patients with 20 cases of acute lymphoblastic leukemia (ALL) and 10 cases of acute myeloid leukemia (AML). The point mutation of CDKN2 gene was analyzed in a PCR generated DNA sequencing technique. RESULTS: There was no point mutation in exon 1 of CDKN2 gene. A missense mutation (G--

Detection of N-myc Amplification with Differential PCR in Neuroblastoma and It's Clinical Significance / 대한소아혈액종양학회지

PURPOSE: The N-myc amplification is one of well known poor prognostic markers in neurblastoma. Because the traditional detection method, Southern blot, is expensive, labor-intensive and time-consuming, the detection of N-myc amplification is not routinely performed in Korea. The purposes of this study are to develop polymerase chain reaction (PCR) for detecting N-myc amplification in neuroblastoma tumor tissue, and to elucidate the clinical significance of N-myc amplification. METHODS: The clinical data and paraffin embedded tumor specimen of 54 neuroblastoma cases were collected from 10 medical centers in Korea. We have developed semiquantitative method of estimating gene copy number that uses differential PCR. N-myc gene primers (RC N-myc, N-myc 7-1) are amplified together with primers from a single-copy internal control gene (beta-globin). After ethidium bromide-stained agarose gel electrophoresis, the ratio of the two PCR products, which stands for N-myc amplification, is determined. Kaplan-Meier survival analysis was performed to evaluate the prognostic significance of N-myc amplification. RESULTS: The differential PCR was very effective, less expensive, less labor-intensive, and simple detection method for N-myc amplification. The percentage of N-myc amplification was higher in the patients older than 1 year old (34.1%: 14/41), when they were compared to the patients younger than 1 year old (16.7%: 2/12). The percentage of N-myc amplification was higher in the patients who have primary tumor at adrenal gland (40.9%: 9/22) than who have primary tumor at retroperitoneum (17.6%: 3/17) or at mediastinum (16.7%: 2/12). In Stage I, II, and III patients, the mean survival time of N-myc amplified group was 18 months and that of N-myc umamplified group was 64 months (Log Rank 4.35, P=0.037). CONCLUSION: The differential PCR was very effective, less expensive, less labor-intensive, and simple detection method for N-myc amplification. The N-myc amplification is one of poor prognostic indicators in Neuroblastoma.

Effects of Low Dose Interleukin-2 Therapy after High Dose Chemotherapy and Autologous PBSCT in Childhood AML and Stage 4 Neuroblastoma / 대한소아혈액종양학회지

PURPOSE: Interleukin-2 (IL-2) exerts anti-cancer effect by increasing NK cell activity when the tumor burden is low. Earlier study conducted with high dose intravenous IL-2 exhibited significant toxicities such as capillary leak syndrome, fever, rash, etc. This study was designed to study the effect of low dose IL-2 in children after autologous PBSCT when the cancer is at minimal level. METHODS: A total of 12 patients (6 AML, 6 NBL) were enrolled in this study from May 1997 to Oct 1999. The age of the patients was between 0.9~15 yr (Median age: 4.35 yr). The AML patients were treated with AML-BFM-87 (5 cases) or CCG-2891 (1 case) protocol, and all the patients underwent autologous PBSCT at CR1. The NBL patients were treated with CCG-3891 (4 cases) or '6 in 1' (2 cases) protocol, and they had operation for residual tumor before PBSCT. The conditioning regimen for AML patients was busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (4 cases) or BCVAC (2 cases), while NBL patients were conditioned with carboplatin (1200 mg/m2), etoposide (800 mg/m2) and melphalan (180 mg/m2). Infused stem cell dose was MNC: (4.5+/-1.7) 108/kg, CD34 : (8.6+/-3.2) 106/kg. IL-2 (Proleukin , Chiron) was started subcutaneously after neutrophil engraftment (ANC<500/mm3) with the dose of 3~5 MU/m2 for the first 2 days, 1MU/m2 for the subsequent 12 days, then followed by 14 days of rest. IL-2 was restarted with the same regimen for more than 6 cycles as outpatient. The CBC, total eosinophil count (TEC) and T lymphocyte subsets were checked before and after IL-2 therapy. RESULTS: The mean neutrophil engraftment was achieved on 12.0+/-3.4 days, and mean platelet recovery to more than 50,000/mm3 was achieved on 23.7+/-10.3 days. Common toxicities associated with IL-2 were fever and mild tenderness on injection site, but there was no need to discontinue IL-2. A total of 75 cycles of IL-2 therapy was given. During follow-up for 8~30 months (median 21 months), only 1 relapse occurred until now (neuroblastoma stage IV). All parameters of T lymphocyte subsets increased after IL-2 therapy. TEC increased in mean value after IL-2 and it was statistically significant (P<0.05). The absolute count of CD4 and CD8 was significantly increased (CD4 : 410 to 640, P<0.005, CD8 : 720 to 980, P<0.05). CD4/CD8 ratio remained reversed (<1) throughout the course of IL-2 in most patients. The total NK cell count was increased from 510 to 820 (P<0.005). CONCLUSION: Low dose IL-2 therapy was well tolerated as OPD basis and there was a significant change in T lymphocyte subsets, especially in NK cell count. Even though the follow up duration was short, the high relapse free survival indicates the beneficial effect of low dose IL-2. In the setting of low tumor burden, such as after autologous PBSCT, low dose subcutaneous IL-2 seems to provide effective anti-cancer effect.

Predictive Values of High Dose Immune Globulin G or Oral Prednisone Therapy for the Splenectomy Response in Patients with Chronic Idiopathic Thrombocytopenic Purpura / 대한소아혈액종양학회지

PURPOSE: The aim of this study is to investigate the usefulness of responsiveness to high dose intravenous immune globulin G (IVIG) or oral prednisone therapy as preoperative predictors for splenectomy response in patients with chronic idiopathic thrombocytopenic purpura (ITP). METHODS: We reviewed retrospectively the charts of 23 patients who were admitted to Yonsei Medical Center, Wonju Christian Hospital, Ajou Medical College Hospital and Pochon CHA General Hospital under the diagnosis of chronic ITP and plenectomized from January 1990 to April 1999, below the age of 20. All of the patients had been treated with high dose IVIG and, or oral prednisone. The responses to the treatments were classified according to Berchtold and McMillan's criteria (1) complete response (CR) 50 103/L. RESULTS: Of 23 patients, 12 boys and 11 girls, the mean age at operation was 12.4 years (5.4~19.4 years), the mean duration from diagnosis to splenectomy was 47 months (6~173 months) and mean follow up was 33 months (3~95 months). Of the 6 patients with responses to oral prednisone, 5 had responses to splenectomy and of the 12 patients with reponses to IVIG, 10 had responses to splenectomy at 3 months. All of 14 patients with no response to oral prednisone and 4 patients with no response to IVIG were responsed to splenectomy at 3 months. Four patients relapsed during follow up and there was no serious complication following splenectomy. CONCLUSION: We concluded that a positive response to oral prednisone or IVIG may be associated with a positive response to subsequent splenectomy and splenectomy is an effective and safe treatment.

Long-term Outcome of Chronic Childhood Idiopathic Thrombocytopenic Purpura according to Therapeutic Methods / 대한소아혈액종양학회지

PURPOSE: Idiopathic thrombocytopenic purpura (ITP) was the most common disease of thrombocytopenic purpura in children, chronic course was shown in 10%. Splenectomy had been used in chronic thrombocytopenic purpura as classic therapy, and many therapeutic method had been tried. We define response to therapy and long-term outcome of chronic childhood idiopathic thrombocytopenic purpura. METHODS: We retrospectively analyzed 41 patients that treated and diagnosed as chronic thrombocytopenic purpura at the Department of Pediatrics, Severance Hospital between Aug. 1981 and Aug. 1999 and followed for mean 8.2 years. The mean age was 6.2 years (range from 1month to 12.3 years) and sex-ratio of male to female was 1:2. According to therapeutic methods, they were divided into splenectomy group, spleen irradiation group, azathioprine group, interferon group, high-dose oral dexamethasone group, vincristine group, intravenous gammaglobulin group, low-dose prednisone group, and low-dose prednisone with intermittent intravenous gammaglobulin group. The results were classified into complete response (CR: platelets> 100,000/mm3), partial response (PR: platelets> 50,000/mm3), no response (NR: platelets <50,000/mm3). RESULTS: The treatment response and number of patients according to therapeutic methods were as follows; splenectomy group, 12 cases (CR-9 cases, PR-1 case, NR-2 cases), spleen irradiation group, 1 case (CR), azathioprine group, 6 cases (CR-1 case, NR-5 cases), interferon group, 3 cases (CR-1 case, PR-1 case, NR-1 case), high-dose oral dexamethasone group, 4 cases (CR-2 cases, PR-1 case, NR-1 case), vincristine group, 2 cases (NR), intravenous gammaglobulin group, 35 cases (CR-5 cases, PR-5 cases, NR-25 cases), low-dose prednisone group, 5 cases (NR), and low-dose prednisone with intermittent intravenous gammaglobulin group, 30 cases (CR-7 cases, PR-3 cases, NR-20 cases). CONCLUSION: The results of therapeutic method in splenectomy group were the most highest score (12 cases: CR-9 cases, PR-1 case, NR-2 cases), high-dose oral dexamethasone group, interferon group, and low-dose prednisone with intermittent intravenous gammaglobulin group in high incidence order. Spleen irradiation was supposed to trial method of treatment before splenectomy, because the risk was lower than splenectomy, although they had 1 case.

Retroviral-mediated IL-2 gene transfer into murine neuroblastoma

We used retroviral-mediated gene transfer of the human interleukin (IL)-2 gene into murine neuroblastoma cells to investigate whether locally-secreted IL-2 is able to influence the generation of anti-tumor immune responses. Supernatant obtained from cultures of approximately 1 x 10(6) IL-2 gene-transduced, G-418 selected neuro-2a cells was assayed for human IL-2 production by ELISA kit. First, to estimate whether the local secretion of IL-2 from the genetically-modified tumor cells would affect their tumorigenicity in vivo, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice and tumor growth was measured weekly. And to estimate whether IL-2 transfected neuroblastoma cells protect mice from tumor development after wild-type tumor cell challenge, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice. Seven days after IL-2 gene-transfected neuroblastoma cell injection, unmodified neuro-2a cells were s.c. injected into the contralateral site of A/J mice and tumor growth was measured weekly. Finally, to estimate IL-2 effect on pre-established large tumor burdens, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice with established tumor and its growth was measured weekly. The IL-2 gene-transduced neuro-2a clones secreted 120.25-177.3 IU of IL-2 per ml per 10(6) cells during 24 hr. None of the mice injected with IL-2-secreting neuro-2a cells developed tumors within 6 weeks, while all of the mice injected with wild-type neuro-2a cells developed tumors. Immunization of mice with IL-2 gene-transfected, irradiated neuro-2a cells protected these animals against a subsequent challenge with wild-type tumor cells. Finally, the size of large neuroblastomas decreased after IL-2-secreting neuro-2a cell injection into mice. Local secretion of IL-2 gene-transduced tumor cells abrogates their tumorigenicity and induces protective immunity and may inhibit the growth of neuroblastoma.

Response to Immunosuppressive Therapy and an HLA-DR Allele in Children with Aplastic Anemia / 대한혈액학회지

BACKGROUND: Genetic susceptibility to a variety of disease has been shown and it has recently been suggested that aplastic anemia is more common in adults who are HLA-DR2+ than in the general population. METHODS: To investigate whether certain HLA-DR gene is more common in children with aplastic anemia and HLA-DR2+ gene is associated with susceptibility to cyclosporine A (CyA), we analyzed the results of HLA-DR typing in 37 children with aplastic anemia with sequence specific oligonucleotide probe (SSOP) method. RESULTS: Eight patients were DR2+, and there was no more common than the normal population. All of the 8 patients with DR2+ were DRB1*1501+ with high resolution HLA typing. Of the 8 patients with DRB1*1501+, 3 patients were treated with CyA alone (2 patients) or CyA plus ATG (1 patient), 2 patients were treated with ATG (1 patient) or ALG alone (1 patient). Patients treated with CyA only or CyA plus ATG had either a complete (1 patient) or partial (2 patients) response and patients treated ATG or ALG alone had no response. CONCLUSION: Although incidence of HLA-DR2 was not significantly higher in children with aplastic anemia then normal population, response rate to CyA was significantly high in the DR2+ patients.

A Case of Monosomy 7 Syndrome Transformed into Acute Myelocytic Leukemia / 대한소아혈액종양학회지

Monosomy 7 syndrome is a rare myeloproliferative disorder of children, and has a clinical presentation similar to JCML. Both syndromes present in children younger than 2 years of age. Pallor, lymphaenopathy, hepatosplenomegaly, recurrent infection, facial rash and petechial bleeding are frequently present. The hematologic picture is characterized by leukocytosis with monocytosis, anemia, thrombocytopenia. It is important to distinguish these two disorders because of their different natural courses. The course of JCML is brief, with most patients dying within 9 months. Patients with monosomy 7 syndrome often present initially with repeated bacterial infections and develop AML after a latent period of 3~6 years. We report a case of monosomy 7 syndrome with typical clinical course in a 3-year-old male patient. The patient experienced a malignant transformation into AML. To our knowledge, this is the first case report of malignant transformation in monosomy 7 syndrome of children in Korea.

A Case of Wilms Tumor in a Horseshoe Kidney / 대한소아혈액종양학회지

Most patients with Wilms tumor do not have associated congenital anomalies. However, significant associations with congenital urinary tract defects, hemihypertrophy, and sporadic aniridia have been reported. Horseshoe kidney is a congenital anomaly in which both kidneys are fused at the lower poles with renal parenchymal or fibrous isthmus. The risk of malignancy in a horseshoe kidney is probably not different from that in a normal kidney. But Wilms tumor are more common in patients with horseshoe kidney than in the general population. We report a case of Wilms tumor arising in a horseshoe kidney with brief review of related literatures.

Clinical Features and Treatment Outcome of Children with Myeloid Antigen Positive Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

Purposes: Leukemic cells from a significant number of children with acute lymphoblastic leukemia (ALL) express the protein antigens which present the characteristic of both lymphoid and myeloid cells. However the clinical significance of this immunophenotype has remained controversial. In this study, we have retrospectively determined the relationship between the myeloid antigen expression and the outcome after the treatment in the patients of newly diagnosed ALL. METHODS: The total number of one hundred and one newly diagnosed childhood ALL patients, who were admitted to the Department of Pediatrics at Severance Hospital from January 1992 to December 1997 were studied. They were classified as the myeloid antigen positive (My Ag+) and myeloid antigen negative (My Ag-), according to the expression of CD13 and/or CD33 antigens on the surface of leukemic cells. Nineteen patients (19%) among them were myeloid antigen positive. RESULTS: There was no difference between My Ag+ and My Ag- patients in favourable presenting features. The remission rate after induction therapy had no difference between My Ag+ and My Ag- patients. Most of all, there was no difference in 4-year event-free survival (EFS) in both groups. Four year-EFS of My Ag+ patients was 82.2% and that of My Ag- patients was 78.7% (P=0.9). The duration of mean survival rate of My Ag+ patients was 51.1 months and My Ag- patients was 67.8 months. Conclusions: We concluded that there was no difference between MyAg+ ALL and MyAg- ALL patients in the outcome of its treatment. In contrast to previous studies, this result was independent of treatment risk category, demonstrating that myeloid antigen expression was not an adverse prognostic factor for childhood ALL.

Prognostic Significance of Circulating Blasts after 7 Day of Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

PURPOSE: To assess the importance of early clearance of blast cells in peripheral blood and the predictability of outcome in childhood acute lymphoblastic leukemia (ALL) through this method. METHODS: We reviewed medical records of all childhood patients with ALL enrolled on Severance Hospital (January 1992 to December 1997) to determine the presence of blast cells in peripheral blood at diagnosis and after 1 week of intensive induction therapy. RESULTS: Persistent circulating leukemic blasts were present at day 7 in 14 patients (11.4%) among 123 ALL patients. Compared with blast negative group, these patients had two adverse clinical and laboratory features (Hemoglobin level and L2 morphology), and a poorer 4-year event-free survival (69.8% vs. 82.7%, P<0.01). CONCLUSION: We found that this simple and noninvasive method, which can replace bone marrow examination, may be very beneficial to predict the prognosis of ALL.

A Clinical Study on Hepatoblasoma in Children / 대한소아혈액종양학회지

PURPOSE: Hepatoblastoma comprises over two-thirds of the malignant tumors of the liver in childhood. Although complete resection is the cornerstone of successful management, combination chemotherapy has had a major impact in improving survival. The purpose of this report is to review the clinical finding, therapeutic response, and long- term result of combined modality in 10 children who diagnosed hepatoblastoma. METHODS: From September 1993 to May 1998, the initial diagnosis of hepatoblastoma was made in 10 children at Severance hospital. We analysed medical record retrospectively for clinical finding, therapeutic modality, and survival. RESULTS: 1) The 10 children ranged in age from 3 months to 51 months of age at diagnosis (median age: 21 months of age). 2) There were 9 boys and 1 girl 3) The children presented with either abdominal distension or a mass. Of 10 patients, 6 patients had thrombocytosis more than 500,000/muL and 7 patients had elevated alpha-fetoprotein (AFP) more than 30,000 IU/mL. 4) Pathology results were predominantly of epithelial histology except one case that had elements of mixed. 5) 7 children had right lobe involvement and one child had tumor in both lobe. 6) Surgery was undertaken at diagnosis in 6 patients and preoperative chemotherapy was taken in 4 patients. Preoperative chemotherapy significantly reduced the extent of resection to be necessary for complete resection in 3 patients. 7) 8 of 10 children (80%) are alive (4 to 51 months posttreatment) with no evidence of disease with median follow-up of 39 months. 2 children are lost to follow-up. Conclusions: Excellent cure rates has been achived with complete resection followed by multiagent chemotherapy for hepatoblastoma. Future studies are directed toward the identification of poor risk patients with protocols designed to improve survival for children with advanced disease.