Epidemiology and Clinical Outcomes in Children with Aplastic Anemia in Korea: Retrospective Study / 대한소아혈액종양학회지

PURPOSE: The annual incidence of aplastic anemia (AA) in Asian countries is higher than in Western countries. The pathogenesis in AA has been investigated in hematopoiesis and immunology. Recently, the survival rate and the quality of life of the patients with AA have been steadily improved by the development of a variety of treatments such as the immunosuppressive therapy (IST), and hematopoietic stem cell transplantation (HSCT). The Korean Society of Pediatric Hematology-oncology retrospectively investigated the incidence, treatment strategies, survival rate, and time to become independent from transfusion in patients with AA, who were diagnosed from January 1st, 1991 to December 31st, 2000 in Korea. METHODS: All the questionnaires were sent to a group of training hospitals, and we collected about 600 questionnaire forms from 27 hospitals. However, 493 reports were available for data analysis. RESULTS: The male and female ratio in AA is 1.1 (259 males vs. 234 female). The median age at diagnosis is 9 years old (range; 0.8~16 years old). The annual incidence of children with AA in Korea is 4.5 per million on the basis of Korean pediatric population. In etiology, there are 20 cases (4.1%) in congenital and others in acquired AA. In acquired AA, the cause of illness was not identifiable for most of the patients, but 1 patient had hepatitis-associated AA, and 3 patients developed the illness after medication. According to the initial laboratory data at diagnosis, the peripheral blood findings showed that hemoglobin is 7.1+/-2.4 g/dL, white blood cell 3, 200/microL (200~16, 550), absolute neutrophil counts 670/microL (0~12, 487), platelets 19, 000/microL (1, 000~500, 000), and corrected reticulocytes 0.18% (0.0~4.7). The bone marrow examination revealed that cellularity was below 25% in 348 patients, and over 25% in 105 patients. In the available data, 269 patients (54.6%) were diagnosed of severe aplastic anemia (SAA) and 224 patients of non-SAA (NSAA). HSCT were done for 96 patients (19.5%) and others received another treatments such as the IST. The anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) treatment was done for 263 cases, corticosteroids for 259, cyclosporine A (CSA) for 215, and anabolic steroids for 138. The combination IST including ATG or ALG plus corticosteroid plus CSA were applied to 154 children with AA, and transfusion only in 37, as conservative care. In case of those patients with HSCT, the time from diagnosis to transplantation was 12 months (1~144 months) and the sources of stem cells were bone marrow in 82 cases, growth factor mobilized peripheral blood in five, and cord blood in six. There were 57 patients transfused below 40 units of blood products before HSC transplantation. Graft rejection was identified from 16 patients, and booster transplantations were done for 12 patients among them. In complications of HSCT, the graft versus host disease was developed in 20 patients and viral diseases in 12 cases including the CMV, herpetic infection, and hepatitis. Also, one patient suffered from veno-occlusive disease. The overall survival rate in children with AA is 64.3%. The survival rate in HSCT is better than that IST (76.9% vs. 62.6%, P< 0.05). In IST, overall survival rate in very SAA showed lower than SAA and NSAA, and in SAA lower than NSAA in case of absolute neutrophil count below 200/microL (P< 0.05). There was no significant difference in terms of the sex, age at beginning of treatment. In HSCT, transfusion was not related to the survival rate. However, overall survival rate is better in short interval between diagnosis and HSCT than in long interval (P< 0.05). There was no significant difference in the probability of transfusion independence according to treatment strategies, even though it was 71.0% in HSCT and 12.8% in immunosuppressive therapy at the end point of survey (P=0.47). The response pattern was as follows. There were 155 cases of complete response, 110 of partial response and 120 of no response in spite of various treatments. The relapse after treatment was found in 11 patients after IST, of which 6 patients experienced more than 2nd relapse. The median time between the end of treatment and relapse was 16 months (6~84 months). Only three cases developed into other diseases (1 case into acute myeloid leukemia and 2 cases into myelodysplastic syndrome). The median time from diagnosis to the end of treatment was 62 months (0.5~174 months). In fatal cases, the median time between diagnosis and death was 29 months (0~144 months) despite several therapeutic strategies. CONCLUSION: In Korea, the annual incidence of children with AA is 4.5 per million. This result is similar to the ones reported in other Asian countries, but higher than those in Western countries. Although a lot of children with AA received various therapies including IST or HSCT, new treatment strategies have to be developed to improve the survival rate and the quality of life of children with AA

Epidemiology and Clinical Outcomes in Children with Malignant Lymphoma in Korea: Retrospective Study / 대한소아혈액종양학회지

PURPOSE: Malignant lymphoma is the primary malignant tumor derived from lymphoid organs. It is composed of Hodgkin's disease and non-Hodgkin lymphoma. Recently, survival rate is on the rise due to improved combination chemotherapy, radiotherapy and high dose chemotherapy followed by hematopoietic stem cell transplantation. In South Korea, no epidemiologic studies concerning malignant lymphoma in the pediatric age group has been performed. Therefore, the Korean Society of Pediatric Hematology-Oncology retrospectively analyzed the incidence, pathologic subtypes, treatment strategies, and survival rates of pediatric malignant lymphomas in South Korea. METHOD: Questionnaires were made and sent to a group of training hospitals, with a return of 580 questionnaires from 24 hospitals. Among them, 517 reports were suitable for analysis. RESULTS: Among the 517 cases, Hodgkin's disease accounted for 58 cases and non-Hodgkin's lymphoma for 459 cases. Male to female ratio for malignant lymphoma was 2.7. Mean age at diagnosis was 8.3 years. Among the pathologic subtypes, mixed cellularity was the most frequent subtype for Hodgkin's disease. Most (70.7%) cases of non-Hodgkins lymphoma belonged to high grade NHL. Burkitt lymphoma accounted for 102 cases, and lymphoblastic lymphoma was found in 58 cases. Peripheral lymphadenopathy was the most common presenting sign upon diagnosis. B symptoms were significantly more frequent in Hodgkin's disease patients than in non-Hodgkin lymphoma patients. The Complete response rate was 62.1% for non-Hodgkin's lymphoma, and 82.8% for Hodgkin's disease. Overall 5 year survival rate was 60.0% in non-hodgkin's lymphoma, and 84.8% in Hodgkin's disease. CONCLUSION: The annual incidence of malignant lymphoma in Korea is 4.7 per million. In cases of chemotherapy-sensitive, refractory or relapsed malinant lymphoma, high dose chemotherapy followed by hematopoietic stem cell transplantation is vital for improved survival. For more systematic analysis of epidemiology on malignant lymphomas, better surveillance mechanisms on the occurrence of malignant lymphomas are crucial, and establishment of standardized treatment protocol for malignant lymphoma is required.

Epidemiology and Clinical Outcomes of Childhood Wilms Tumor in Korea / 대한소아혈액종양학회지

PURPOSE: Wilms tumor is the most common malignant renal tumor in children. We investigated the epidemiology, clinical features and treatment outcome of the children with Wilms tumor in Korea during the recent 10 years. METHODS: Two hundred forty six patients were enrolled between January 1991 and December 2000 from 26 major hospitals in Korea. The data regarding the clinical features including sex, age, pathologic type, prognostic factor 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 were analyzed by log-rank test. RESULTS: There were 130 males and 116 females. The incidence between the age of 1~4 years was the highest with 66.2%. The annual incidence rate per 1, 000, 000 population varied from 1.9 to 2.1. The 10 years overall survival rate according to sex, clinical stage, pathologic type and relapse were as follows: 88.6% in male, 90.9% in female, 100% in stage I, 94.7% in stage II, 92.1% in stage III, 63.4% in stage IV, 85.7% in stage V, 95.3% in favorable histology, 64.1% in unfavorable histology, 94.8% in non-relapse, and 40.9% in relapse. The relapse rate was 12%. The 10 years overall survival rate of 246 patients were 89.1%. CONCLUSION: Our results could provide the most recent and important clinical information on Wilms tumor of children in Korea.

Childhood Acute Immune Thrombocytopenic Purpura in Korea: Multicenter Study of Korean Society of Pediatric Hematology/Oncology / 대한소아혈액종양학회지

PURPOSE: Childhood acute immune thrombocytopenic purpura (ITP) is a benign hematologic disease. Therapy does not affect the natural history of the illness. We evaluated the clinical and laboratory findings, treatment and prognosis of childhood acute ITP in Korea through a retrospective multicenter study. METHODS: We analyzed retrospectively the data of 1, 829 children with acute ITP through survey of 33 hospitals among 43 hospitals in Korea from Sep. 1992 to Aug. 2001. RESULTS: Male to female ratio was 1.3: 1 and the median age at the diagnosis of ITP was 2.9 (0.1 17) years. Median duration of follow up was 6 months. One hundred and forty nine cases of the total 1, 829 patients (8.1%) received no treatment. The initial median platelet count of the non-treated group was 42, 500/mm3. Among the 861 cases who were followed up over 6 months, 315 cases (36.6%) progressed into chronic ITP. Associated with this high rate of chronicity of childhood acute ITP patients in Korea, we must consider the fact that acute ITP patients with fast improvement in the first episode tend not to follow up. Considering that fact, the rate of chronicity becomes 17.2% of the 1, 829 acute ITP patients. The treated group used many kinds of treatment methods. Intravenous immunoglobulins (IVIG) with or without prednisolone (PD) (67.5%) were the most commonly used regimens. In the group treated with IVIG alone, the platelet count began to rise above 50, 000/mm3 at 2.6 days, 100, 000/mm3 at 3.7 days and 150, 000/mm3 at 4.9 days. Four hundred and twenty two cases of the 1, 686 (25.0%) cases followed up after first episode of ITP relapsed. The relapse rate was significantly higher in older patients and in girls than in younger patients and in boys (P< 0.05). The chronicity of ITP statistically increased with age (P< 0.05) and that was the only valuable factor. CONCLUSION: Despite the fact that childhood acute ITP is a pretty common disaese, there is no agreement on the best treatment method for this disease. The establishment of Korean treatment guideline of childhood acute ITP, based on an analysis of multicenters, seems to be needed.

Effect of Leukokine in Patients with Acute Leukemia Receiving Induction Chemotherapy / 대한소아혈액종양학회지

PURPOSE: Neutropenia is common in patients receiving myelotoxic chemotherapy. The aim of this study is to compare the efficacy, safety and adverse events between prophylactically administered Leukokine and Grasin. METHODS: An open-label, randomized, phase III study was designed to compare the effects of a subcutaneous injection of Leukokine (CJ Corp.) 100mug/m2 with Grasin (Jeil Pharm. Inc.) in patients receiving induction chemotherapy for acute leukemia. All patients received one dose of G-CSF every day during the study period. Total period of G-CSF injection was not over 14 days. The administration of G-CSF began on day 14 after beginning of chemotherapy under CCG strategy. In other chemotherapies, the injection of G-CSF started on day 1 from end of chemotherapy. Injection of G-CSF stopped after absolute neutrophil count recovery was achieved. RESULTS: The median numbers of times of administration were 9.6 (2~14) /cycle for Leukokine and 8.8 (2~14) /cycle for Grasin. The time to needed for neutrophil recovery more than 1, 000/mm3 was 6.6 4.9 day and 4.7 4.8 day of the Leukokine and Grasin, respectively (P=0.14). The mean duration of neutropenia less than 500/mm3 was 7.6 5.6 days for Leukokine and 6.1 6.0 days for Grasin (P=0.28). The results for the two groups were also not significantly different in adverse events, physical examination and laboratory findings. CONCLUSION: Leukokine was safe and well tolerated in these patients population. Injection of Leukokine provided neutrophil recovery with safety and efficacy similar to that provided by Grasin.

Influence of Prognostic Factors on Survival Rate of Medulloblastoma Patient with Chemotherapy

PURPOSE: Brain tumors are the second most common tumor in childhood, and medulloblastomas comprise 15-25% of brain tumors. The well known prognostic factors are age at diagnosis, stage of disease, and extent of surgical excision. In this study, we analysed the prognostic factors in patients who received chemotherapy after excision. METHODS: We reviewed the medical records of 61 patients who received chemotherapy among the 94 patients who were diagnosed and treated between Jan 1985 and Sep 2001 in the Department of Pediatrics and Neurosurgery at Severance Hospital. RESULTS: Among the total survival rate of patients who underwent chemotherapy, the 3-yr progression-free survival rate was 66.5+/-6.3% and the 15-yr progression-free survival rate was 60.3+/-6.7%. The progression-free survival rate for patients with age at diagnosis over 3 yrs old and under 3 yrs old, was 64.5+/-7.7% and 48.2+/-12.9% respectively and there was no statistically significant difference. The survival rate of the high vs low risk group by staging was 72.7+/-10.5% and 54.6+/-8.3% respectively, and there was no significant difference. The survival rate of patients with total removal vs subtotal removal was 65.8+/-11.8% and 56.8+/-8.2% respectively, showing no statistical difference. CONCLUSION: The reason there is no difference in survival rate according to the traditional prognostic factors is that chemotherapy has improved not only the total survival rate but also the survival rate in patients with poor traditional prognostic factors. So, sufficient removal of tumor followed by proper chemotherapy and radiotherapy is an important factor which influences the survival rate of medulloblastoma patients.

Results of Treatment for Children with Primary Brain Tumors: Long-Term Follow Up Results of a Single Institute

PURPOSE: Brain tumors are the most common solid tumor in children. We retrospectively investigated the clinical characteristics of pediatric brain tumors, such as age, sex, tumor site and survival, as seen in a single institution over the last 15 years. We tried to evaluate the role of chemotherapy on the survival of some brain tumors. METHODS: Three hundred fifty four children with primary brain tumor who were treated at Severance Hospital from Jan. 1985 to Sep. 2001 were enrolled. RESULTS: Pediatric brain tumors were found most frequently in 10-15 years of age group(35.3%) and the ratio of male to female was 1.3 : 1. Supratentorial tumors(52%) were more frequent than infratentorial tumors(48%). Medulloblastoma/primitive neuroectodermal tumor(PNET) was the most common type(24.6%), followed by cerebellar astrocytoma(14.1%). Ten year survival rate of medulloblastoma, cerebellar astrocytoma and cerebral astrocytoma were 59.4%, 79.3% and 71%, respectively. The prognosis for brain stem glioma and glioblastoma multiforme were still grim with a 10 year survival rate of 12.7% and 13.3%, respectively. The addition of chemotherapy for high grade medulloblastoma led to an improved 10 year survival rate of 54.5%, compared with 40% without chemotherapy. CONCLUSION: The combined use of chemotherapy and radiation and surgery improved survival rate of pediatric brain tumors in our study. Chemotherapy for high grade medulloblastoma improved the 10 year survival rate. Further data analysis of the treatment modalities will lead to better comparisons.

A Case of Subcutaneous Panniculitis-like T Cell Lymphoma in Childhood

Subcutaneous pannicultis-like T cell lymphoma is a rare cutaneous T cell lymphoma. It presents with multiple subcutaneous nodules or plaques involving the extremities or trunk, and with constitutional symptoms that include fever, malaise, fatigue, myalgia, chills and weight loss. Histologically, the lesions of this disease are reminiscent of panniculitis and are composed of a mixture of small and large atypical lymphoid cells infiltrating between adipocytes. The optimal treatment for this disease is undefined and prognosis of this disease is poor, even when treated with multiagent chemotherapy regimens considered optimal for agressive lymphoma of other types. Poor prognosis factors include clinical features such as anemia, leukocytopenia, hepatosplenomegaly, lymphadenopathy and coagulopathy, which are suggestive of hemophagocytosis. Much of the mortality of this disease is due not to disseminated lymphoma with organ failure, but rather to complications of the cytopenias associated with the hemophagocytic syndrome. We report a case of subcutaneous panniculitis-like T cell lymphoma in a 12 year-old boy who presented with initial complaints of fever and multiple subcutaneous nodules, and briefly review the related literature.

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.

A Comparative Analysis between Flow Cytometry and RT-PCR Methods for the Detection of Minimal Residual Disease in Neuroblastoma / 대한소아혈액종양학회지

PURPOSE: A sensitive assay to detect minimal residual disease in neuroblastoma is necessary for accurate assessment of disease status and optimal treatment. In this study, we compared the usefulness of sensitive methods, flow cytometry and RT-PCR for the detection of minimal residual disease in neuroblastoma. METHODS: Eighteen patients who were newly diagnosed and treated at Severance Hospital since 1999 were included in this study. Samples from bone marrow, peripheral blood, and peripheral blood stem cell product were examined for tumor cell contamination by RT-PCR (TH RT-PCR) to detect tyrosine hydroxylase mRNA and by flow cytometry identifying CD9+/CD56+/CD45- cells. RESULTS: We analyzed 20 cases from 18 patients, which were assayed by both methods at the same time. Among 20 cases, 16 cases showed same results, which were compatible with histologic results and clinical course, and 4 cases showed different results. One case of them showed positive result in histology and flow cytometry, but negative result in TH RT-PCR. The other 3 cases showed negative results in flow cytometry, but positive results in TH RT-PCR, and 1 patient of them relapsed. Among 16 patients, 2 patients, showing positive results in only TH RT-PCR, relapsed. CONCLUSION: Detection of minimal residual disease using TH RT-PCR and flow cytometry was effective and useful in evaluating disease status and deciding for proper treatment.

A Successful Transplant of HLA-3 Loci Mismatched Umbilical Cord Blood into a Patient with Acute Myeloid Leukemia from an Unrelated Donor

Cord blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution. The number of umbilical cord blood transplants is increasing worldwide. In this a case 15- month-old boy with acute myeloid leukemia was treated with umbilical cord blood transplant from an HLA-3 loci mismatched unrelated donor. Granulocyte recovery greater than 500/mm3 occurred at day 49, and the platelet recovered greater than 20,000/mm3 independent of transfusion at day 81 after stem cell infusion.

A Case of Wilms Tumor with Thrombi which Invaded the Right Ventricule

Wilms tumor is the second most common malignant retroperitoneal tumor. Inferior vena cava and right atrial involvement is found in about 4-10% and 0.5-3% of cases, respectively. But, right ventricular involvement has not been reported. We experienced a case of Wilms tumor with right ventricular invasion in a 2 year-old male who presented intermittent hematuria and abdominal pain. Computed tomogram and echocardiogram showed a homogeneous mass extended to right ventricle via inferior vena cava. He received pre-operative chemotherapy followed by operation, radiation therapy including heart, and post-operative chemotherapy.

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.

Patterns of Relapse and Survival for Neuroblastoma / 대한소아혈액종양학회지

PURPOSE: Nowadays, survival of neuroblastoma patients has improved by high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). But, many of these patients experienced treatment failure, and relapse was the most important factor of treatment failure. The aim of this study was to investigate the relation between pattern of relapse and survival of neuroblastoma for 10 years. METHODS: Fifty nine neuroblastoma patients were enrolled in the study. Retrospective investigation of medical records was performed. RESULTS: Twenty two patients experienced relapse among total 59 patients. Two patients had relapse two times, and another two patients had two or more relpase sites. Median time from diagnosis to relapse is 16.8 months (2~40 months). According to International Neuroblastoma Staging System (INSS), stage of patients with relapse at diagnosis is as follows; Stage II-2 patients, Stage III-4 patients, and Stage IV-16 patients. 11 patients received high dose chemotherapy followed by autologous PBSCT, and 7 patients (63.6%) of them experienced relapse. 48 patients received only chemotherapy, and 17 patients (35.4%) of them experienced relapse. Sites of relapse are as follows; central nervous system (CNS) 6 patients (22.2%), primary site 4 patients (14.8%), bone 4 patients (14.8%), bone marrow 4 patients (14.8%), distant lymph node 2 patients (7.4%), liver 2 patients (7.4%), and others 5 patients (18.5%). CONCLUSION: In this study, relapses were observed in about 37% of cases. And, the more relapse, the lesser survivals are observed. Although this single institution result had limitation to generalize, CNS was the most common site of relapse. However, multi-center study for relapse sites of neuroblastoma should be evaluated further.

Long-term Follow up of Wilms Tumor / 대한소아혈액종양학회지

PURPOSE: With the use of combined-modality therapy, the survival of the patients with the Wilms tumor has been improved during past 30 years. We reviewed the clinical characteristics and treatment outcome of pediatric Wilms tumor patients diagnosed during recent 20 years' period and compared this data with previous reports. METHODS: From June 1979 to April 2000, 61 patients were diagnosed with Wilms tumor. Retrospective analysis of the medical records of these patients was performed. RESULTS: A male to female ratio was 1.2:1. Median age at diagnosis was 3 years 2 months. Initial symptoms at diagnosis were abdominal mass (85.3%), gross hematuria (9.8%) and abdominal pain (4.9%). The two major pathologic types of Wilms tumor were favorable (80.4%) and unfavorable (19.6%) histology. The number of patients by staging according to National Wilms Tumor Study (NWTS) Group was as follows: Stage I 27.8% (17/61), Stage II 23.0% (14/61), Stage III 26.2% (16/61), Stage IV 19.7% (12/61) and Stage V 3.3% (2/61). The incidence of recurrence in Wilms tumor has been reported to be about 18.0% (11/61). The most common sites of relapse are the lung and abdomen. Among 61 patients, 10-year overall survival rate was 70.6%. According to histology, 10-year overall survival rate was 80.2% in favorable group and 28.0% in unfavorable group. The 10-year overall survival rate of was 59.4% from 1979 to 1990 and 83.9% from 1991 to 2000. The 10-year survival rate from 1979 to 1990 by staging was as follows: Stage I 83.3%, Stage II 66.6%, Stage III 60.0% and Stage IV 44.4% The 10-year survival rate from 1991 to 2000 by staging was as follows: Stage I 100%, Stage II 83.3%, Stage III 100% and Stage IV 50.0%. CONCLUSION: The clinical characteristics, histology, relapse and treatment outcome was similar to those reported by NWTS. There has been marked improvement of survival in Wilms tumor over the past 20 years. Despite the remarkable success in the treatment of Wilms tumor, there are still as a small patients who will suffer a relapse.

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--