Immunomodulation Therapy in Aplastic Anemia: Relapse Rate, Complications and Long-term Survival During Follow-up for More than 1 Year

PURPOSE: We evaluated the response to immunomodulation therapy, long-term survival and relapse rate of aplastic anemia during follow-up for more than 1 year. METHODS: Twenty-eight children, with moderate to severe aplastic anemia were followed for more than one year and 7 children expired after therapy, were analyzed. Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) by itself was given to 27 patients, and cyclosporine A (CsA) combined with ALG was given to 8 patients. ALG (ATG) was administered for 8 days in 20mg/kg/day when used alone, and for 5 days in 10mg/kg/day when combined with CsA. CsA was orally administered on the 14th day till 180th day of therapy, with 5mg/kg/day for first 14 days and 3mg/kg/day thereafter. RESULTS: Fifteen out of 35 patients (43%) showed a response. Median interval to response was 3 month (1-40 months). Response rate to ALG + CsA was 50%, compared to 41% in ALG (or ATG) alone. The interval of aplastic anemia symptoms to treatment showed a tendency to be shorter in responders (4.1 +/- 2.2 months) than in non-responders (17.5 +/- 6.4 months). Relapse occurred in 3 of 15 responders (20%). Evolution to secondary clonal hematologic disorders was not observed. Overall actuarial survival at 3 year was 78.2%. CONCLUSION: The results of immunomodulation therapy suggest that response would be better for patients whose interval from symptoms of aplastic anemia to treatment is short. Our results also suggest that ALG+CsA would be a better treatment modality to improve response rate.

A Result of Treatment of 'Eight Drugs in a Day' in Medulloblastoma: Comparison between Pre- vs Post-Irradiation Chemotherapy / 대한소아혈액종양학회지

BACKGROUND: 'Eight drugs in a day' was one of the widely used regimen in medulloblastoma. Result of treatment of this regimen and comparison between pre-RT chemotherapy and post-RT chemotherapy were presented. METHODS: Medical records of children who were diagnosed as medulloblastoma and treated with 8 in 1 therapy in Seoul National University Children's Hospital from January 1986 to June 1997 were reviewed. RESULTS: 1) Forty nine cases(male: 30, female: 19) were analyzed. The age at diagnosis was between 3 months and 15 years 3 months and median age was 7 years 10 months. 2) The T stage by Chang classification revealed T1(2%), T2(26%), T3a(9%), T3b(56%), and T4(7%) in 43 cases. M stage revealed M0(46%), M1(15%), M3(37%), and M4(2%) in 41 cases. The surgical results revealed gross total resection(36%), near total resection(18%), subtotal resection(38%), and partial resection(9%). 3) The 5-yr disease free survival(DFS) rate of all tumors was 53%. There was no difference in DFS about sex, age, pathology, T stage, M stage, and surgical result. 4) Difference of 5-year DFS between pre-RT chemotherapy group(53%) and post-RT chemotherapy group(83%) was significant[-2Log(LR), P=0.023], excluding the patient relapsed or too young(below 18 month, who had more chemotherapy to delay radiation) to be received radiation therapy. CONCLUSIONS: DFS in post-RT chemotherapy was better than pre-RT chemotherapy. As medulloblastoma has the property to confine in CNS system, prior treatment with radiation as a intensive local therapy may be more effective than the systemic chemotherapy. Progression or relapse were the main causes of treatment failure. Result of treatment may be improved by more intensive therapy.

The Combined Therapy of Peripheral Primitive Neuroectodermal Tumor in Childhood / 대한소아혈액종양학회지

PURPOSE: A review of the literature for patients with peripheral primitive neuroectodermal tumor (PPNET; peripheral neuroepithelioma) suggests that the outcome is usually poor. We performed a retrospective study to emphasize the need for triple combined therapy of PPNET. METHODS: The clinical data of 10 patients (M:F=1:1, aged 1 8/12~14 3/12 years) with PPNET seen at Seoul National University Children's Hospital from Jan. 1991 to Jun. 1998 were reviewed. RESULTS: The primary sites were head and neck, chest, limbs, and retroperitoneal area in order of frequency. A palpable mass was the major symptom. The median duration of symptoms before diagnosis was 3 months. Metastatic disease at diagnosis was found in 3 patients, 2 of them were multiple. All of the patients had combined modality treatment with surgery, chemotherapy and radiation therapy. The 3-year relapse-free survival rate was 64%, and the overall 5-year survival rate was 66%. CONCLUSION: Best results were obtained with combined therapy with combination chemotherapy, extensive surgery and local radiation therapy.

Induction Chemotherapy with BH-AC, Idarubicin, and 6-Thioguanine in Childhood Acute Myelogenous Leukemia

PURPOSE: We have undertaken this study to evaluate the effects of induction chemotherapy involving BH-AC, idarubicin, and 6-thioguanine (6-TG). METHODS: BH-AC 300mg/m2/day was administered intravenously over three hours for seven consecutive days. Idarubicin 12mg/m2/day was administered intravenously for three days. 6-TG 100 mg/m2/day was administered orally for seven days. Intrathecal ara-C was administered on the first day of treatment. RESULTS: Complete remission (CR) was achieved in 18 cases (66.7%), partial remission (PR) was achieved in 2 cases (7.4%). In previously untreated patients, complete reimission rate was 92.9% (13/ 14), in relapsed patients, 40% (2/5) and in the refractory patients, 37.5% (3/8). The remission duration until December 1996 was 45 to 630 days (median 133). Duration of the neutropenia (ANC<500/microliter) was 0 to 38 days (median 24). Side effects were nausea, vomiting (7/27, 25.9%), liver dysfunction (1/27, 3.7%), skin eruption (1/27, 3.7%), and mucositis (1/27, 3.7%). In all cases, fever developed in the neutropenic state (culture proven sepsis in 5 cases). Death occurred in 5 cases who achieved CR due to sepsis after chemotherapy (4 cases), intracerebral hemorrhage after bone marrow relapse (1 case). CONCLUSION: BH-AC, idarubicin, and 6-TG induction chemotherapy could be a useful induction chemotherapy treatment that combines supportive care for infection and bleeding.

Testicular Involvement in Childhood Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

BACKGROUND: The testes are one of the most common extramedullary sites of relapse in boys with acute lymphoblastic leukemia(ALL). The reported incidence of isolated testicular relapse varies from 3 to 40%. If these patients are treated exclusively with testicular irradialion, a systemic relapse occurs within a few months. Recently, the use of intensive chemotherapy and testicular irradiation improved the survival rate for boys with testicular leukemia. So, we performed this study to identify clinical manifestations, disease free survival and prognostic factors of testicular leukemia in children. METHODS: We reviewed 33 patients of testicular leukemia among total 410 boys with ALL diagnosed at the Department of Pediatrics, Seoul National University Children's Hospital from Jan. 1970 to Aug. 1996. Testicular leukemia was confirmed by testicular biopsy in all 33 patients. These patients were treated with combined local testicular irradiation(2,400~2,500 cGy/8~12fractions) and systemic chemotherapy. Two patients, in whom testicular relapse was diagnosed before 1979, unilateral orchiectomy of the involved site and testicular irradiation of the opposite site were performed. Probability estimates of disease free survival (DFS) were calculated by the method of Kaplan and Meier, and the relationship of prognostic factors to DFS was compared using the chi-square test in survival analysis. RESULTS: In 410 boys with ALL, testicular leukemia occurred in 33 patients(8%). Of 33 patients, 6 patients presented with testicular involvement at initial diagnosis, 16 patients had testicular relapse while still receiving chemotherapy and 11 patients had testicular relapse 3 to 57 months(median : 15 months) after cessation of chemotherapy. The median age of 33 patients was 7.4 yrs(9 months~18 yrs) and median WBC count 7,600/ L(2,700~270,000/L). All patients presented with painless testicular enlargement and testicular leukemia was confirmed by testicular biopsy. Among 33 patients, 2 had prior CNS relapse and 11 had concomitant bone marrow and/or CNS relapse. Twenty nine patients were treated with combined local testicular irradiation and systemic chemotherapy. Eleven had second relapse(6 bone marrow, 3 CNS, 2 opposite testis). Seventeen have been followed until now: 6 patients on chemotherapy and 11 patients(37.9%) in complete remission for 48.5+/-22.3 months(19~86 months). The 3 year DFS for 29 patients was 55.3%+/-10.1%. The following prognostic factors showed no significant association with DFS in testicular relapse : age and WBC count at initial diagnosis, age at testicular relapse, and concomitant relapse. Whether testicular relapse occurred on initial therapy or off initial therapy has prognostic value in predicting DFS. The 3 year DFS for boys with testicular relapse on and off initial therapy were 40.0%+/-12.9% and 78.8%+/-13.4%, respectively(P: 0.046). CONCLUSION: With the use of chemotherapy and testicular irradiation, prolonged second re mission can be achieved in many patients with testicular leukemia. The patients with testicular relapse off initial therapy fared significantly better than patients on therapy. So, to improve the DFS for boys with testicular leukemia, a better understanding of its biology and prognostic factors is needed.

A Result of Treatment of Malignant Germ Cell Tumors in Childhood

PURPOSE: Germ cell tumors have variable clinical characteristics according to the age, sex, primary site, and pathologic diagnosis. To provide the therapeutic principle, the clinical characteristics, response to the treatment, and prognostic factors were analyzed. METHODS: Medical records of 57 children who were diagnosed as malignant germ cell tumor in Seoul National University Children's Hospital from January 1986 till June 1996 were reviewed. RESULTS: 1) Fifty seven cases (male : 22, female : 43, true hermaphrodite : 1) were analyzed. The age of diagnosis was between 2 months and 15 years and median age was 4 year 7 month. 2) The primary sites were sacrococcygeal area (28%), intracranial area (25%), ovary (18%), testis (11%), retroperitoneum (7%), and mediastinum (4%) in order of frequency. Another cases were in liver, spinal cord, skull base, tongue, and ovary & testis in hermaphrodite. 3) Pathologic diagnosis was possible in 53 cases. Mixed germ cell tumor (37%), endodermal sinus tumor (23%), germinoma (13%), immature teratoma (8%), embryonal carcinoma (4%), and choriocarcinoma (2%) were included in order of frequency. 4) The stage by CCG/POG classification revealed that 6% of stage I, 19% of stage II, 43% of stage III, and 32% of stage IV in 53 cases. 5) After the initial surgery or needle biopsy, radiation therapy was done in the intracranial tumor with EP induction or modified CCG 8891, etc. and cis-VAB, EP, VAB-3, VAC, or CCG 8891, etc. was done in the extracranial tumor with/without radiation therapy. 6) The response rate revealed that 71% of complete response, 22% of partial response, and 7% of progressive disease in 45 cases. 7) The response rate was related to the primary site but not pathology and stage. All the gonadal tumors had complete response. 8) The 5 year-survival rate of all malignant germ cell tumors was 73%. Stage 4 or sacrococcygeal tumor had poor survival rate. CONCLUSIONS: Stage 4 and sacrococcygeal area were thought as the poor prognostic factors affecting survival. Survival rate of tumors at sacrococcygeal area were poor owing to the relatively younger age of onset, and poor response rate. The 5 year-survival rate of tumors treated with cis-VAB were 74% but shown complications frequently. So BEP will be preferred.

A Result of Treatment of Malignant Germ Cell Tumors in Childhood

PURPOSE: Germ cell tumors have variable clinical characteristics according to the age, sex, primary site, and pathologic diagnosis. To provide the therapeutic principle, the clinical characteristics, response to the treatment, and prognostic factors were analyzed. METHODS: Medical records of 57 children who were diagnosed as malignant germ cell tumor in Seoul National University Children's Hospital from January 1986 till June 1996 were reviewed. RESULTS: 1) Fifty seven cases (male : 22, female : 43, true hermaphrodite : 1) were analyzed. The age of diagnosis was between 2 months and 15 years and median age was 4 year 7 month. 2) The primary sites were sacrococcygeal area (28%), intracranial area (25%), ovary (18%), testis (11%), retroperitoneum (7%), and mediastinum (4%) in order of frequency. Another cases were in liver, spinal cord, skull base, tongue, and ovary & testis in hermaphrodite. 3) Pathologic diagnosis was possible in 53 cases. Mixed germ cell tumor (37%), endodermal sinus tumor (23%), germinoma (13%), immature teratoma (8%), embryonal carcinoma (4%), and choriocarcinoma (2%) were included in order of frequency. 4) The stage by CCG/POG classification revealed that 6% of stage I, 19% of stage II, 43% of stage III, and 32% of stage IV in 53 cases. 5) After the initial surgery or needle biopsy, radiation therapy was done in the intracranial tumor with EP induction or modified CCG 8891, etc. and cis-VAB, EP, VAB-3, VAC, or CCG 8891, etc. was done in the extracranial tumor with/without radiation therapy. 6) The response rate revealed that 71% of complete response, 22% of partial response, and 7% of progressive disease in 45 cases. 7) The response rate was related to the primary site but not pathology and stage. All the gonadal tumors had complete response. 8) The 5 year-survival rate of all malignant germ cell tumors was 73%. Stage 4 or sacrococcygeal tumor had poor survival rate. CONCLUSIONS: Stage 4 and sacrococcygeal area were thought as the poor prognostic factors affecting survival. Survival rate of tumors at sacrococcygeal area were poor owing to the relatively younger age of onset, and poor response rate. The 5 year-survival rate of tumors treated with cis-VAB were 74% but shown complications frequently. So BEP will be preferred.