Hideko Tasaka

Mass screening for neuroblastoma at 6 months of age: Difficult to justify

BACKGROUND/PURPOSE A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. METHODS The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. RESULTS From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). CONCLUSIONS These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.

Mass screening for neuroblastoma: quo vadis? A 9-year experience from the Pediatric Oncology Study Group of the Kyushu area in Japan.

Since 1985, a nationwide program of mass screening for neuroblastoma has been available for 6-month-old infants throughout Japan. From 1985 to 1993, the authors studied 285 patients with neuroblastoma among their regional population of 15 million. There was an increase in the total number of patients per year in comparison to the previous 6-year period (1979 to 1984). However, no significant difference was noted in the number of patients older than 1 year or in the incidence of advanced-stage (stages III and IV) unscreened cases. The majority of neuroblastomas in the screened group showed favorable biological factors, even in the advanced stages. However, there was a small group with histologically and/or biologically unfavorable factors; five of 115 had amplified N-myc oncogene, four of 74 showed unfavorable Shimada histological findings, and three of 33 had an unfavorable DNA ploidy pattern. One case from this group with unfavorable factors died of the tumor. 3) Thirty-eight cases were negative at the time of mass screening, but later presented with neuroblastoma. Most of them were diagnosed between 1 and 3 years of age, and 30 of the 38 cases (78.9%) were advanced stage with unfavorable prognostic factors. Thus, the authors conclude that mass screening at 6 months can detect a selected population of infants with neuroblastoma; some of the tumors may represent subclinical masses destined for spontaneous regression. However, some tumors with unfavorable factors have been detected by mass screening before progression and/or dissemination. Infants in this group are considered to benefit most from early diagnosis and treatment.

Acute promyelocytic leukaemia in a patient treated with etoposide for Langerhans cell histiocytosis.

Summary. We report a child with acute promyelocytic leukaemia (APL) who was treated with etoposide (VP16) for Langerhans cell histiocytosis (LCH). A 3‐year‐old Japanese girl was diagnosed as having LCH. She was treated with combination chemotherapy using VP16 and prednisolone. 56 months after beginning the chemotherapy she developed APL. Her bone marrow was occupied with atypical promyelocytes including giant granules and multiple Auer bodies. A cytogenetic analysis of the leukaemic cells showed 46, XX,11–,14q +, t(15,17). The cumulative dose of the administered VP16 was 12120 mg/m2, which suggested that VP16 may be responsible for the development of APL. The risk of developing secondary leukaemia after the administration of VP16 should therefore be considered when managing patients with LCH.

Improved survival rates in children over 1 year of age with stage III or IV neuroblastoma following an intensive chemotherapeutic regimen

Combined chemotherapeutic regimens of (1) cyclophosphamide (40 mg/kg x two days), (2) cisplatinum (20 mg/m2 x five days) plus VM-26 (100 mg/m2), and (3) Adriamycin (60 mg/m2) plus DTIC (250 mg/m2 x five days) were prescribed for 42 Japanese children greater than 1 year of age with stage III or IV neuroblastoma. The protocol was separated into three forms (A, B, and C) from the combination pattern of three such high-dose courses. The cumulative survival rates for those with stages III and IV 48 months after initiation of therapy were 76.2% and 20.1%, respectively, and the overall rate was 36.7%. The tumor disappeared during the course of treatment in 25 of 42 children (59.5%). The 48-month survival rate was superior in patients greater than 5 years of age than younger patients (P less than .01). Even in patients with a tumor originating in the suprarenal region, the 48-month survival rate was 30.5%. Among 12 patients in whom the N-myc oncogene was measured, one of five with one to ten copies of amplification died, whereas all seven with greater than ten copies died or had a recurrence. Thus, the present chemotherapeutic regimens, in particular alternate administration of each high-dose course, considerably improved the survival of patients with stage III neuroblastoma. More aggressive protocols are needed for those with stage IV neuroblastoma who are greater than 1 year of age, particularly in those with an amplified N-myc oncogene.

How to deal with advanced cases of neuroblastoma detected by mass screening: A report from the pediatric oncology study group of the Kyushu area of Japan☆

Since 1985, a nationwide program of mass screening (MS) for neuroblastoma has been underway for 6-month-old infants throughout Japan. As a result, the number of patients with stage I or II disease has obviously increased, and this has resulted in overall improvement of the prognosis for neuroblastoma. Some cases detected by MS were already in an advanced stage and have also had a good prognosis. In such cases, no definitive treatment protocol has been developed. Therefore, the authors investigated (1) the clinical and biological features of the advanced neuroblastoma cases detected by MS and (2) the best way to deal with such cases. The authors analyzed 94 cases of advanced-stage neuroblastoma registered in the Kyushu area (population, 15 million) between 1985 and 1990. Eighteen cases (16 stage III, 2 stage IV) were found by MS, and the others (23 stage III, 53 stage IV) were diagnosed clinically. The following results were obtained: (1) No N-myc amplifications were observed in cases detected by MS, whereas 16 of the 45 examined patients in the non-MS group had high amplifications of N-myc. (2) With regard to Shimadas classification, DNA content, and S-100 protein positivity, most of the advanced tumors found by MS showed characteristics indicating a good prognosis. (3) The 5-year survival rate for the non-MS group is less than 25%, whereas all of the patients whose tumors were detected by MS are alive, even after undergoing mild chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Herpes zoster in children with bone marrow transplantation: Report from a single institution

Herpes zoster (HZ) has been often observed after bone marrow transplantation (BMT) in childhood. The occurrence of HZ was reviewed in children who received BMT. The clinical features of HZ were reviewed in 44 children who underwent BMT at Kyushu Cancer Center. Among the 35 recipients with a history of varicella before BMT, several factors associated with BMT and the lymphocyte subsets were compared between the patients who developed HZ (HZ + group) and those who did not (HZ‐ group). Twenty‐two recipients (50%) developed HZ; in two‐thirds of these cases (15/22: 68%), HZ occurred between 80 and 120 days after BMT (median 101 days). The recipients treated with busulfan had a higher occurrence of HZ than those treated without it. The patients with Grade II‐IV acute graft‐versus‐host disease (GVHD) developed HZ more frequently. In the HZ + group, the absolute number of lymphocytes, CD3+, CD4+ or CD8+ cells at 3 months was significantly lower than that observed at 12 months after BMT and the CD4/CD8 ratio was significantly lower at 1 month than after 3 months of BMT. In conclusion, recipients were susceptible to HZ at around 100 days after BMT. The development of HZ may be associated with unbalanced T lymphocytes at that time.

Characterization of new non-T, non-B acute lymphoblastic leukemia cell lines: Analysis of surface antigens by quantitative cellular radioimmunoassay and flow cytometry☆

Two novel acute lymphoblastic leukemia (ALL) cell lines, HOON and HYON, have been established from patients with non-T, non-B ALL. The cell lines have been characterized and shown to express phenotypic markers on non-T, non-B ALL. By indirect immunofluorescence and flow cytometry they express Ia and common ALL (CALLA) antigens and are reactive with monoclonal antibodies BA-1, BA-2 and OKT-9. However, the cells do not express detectable amounts of B1 antigen or of cytoplasmic mu chain, which are markers of pre-B cells. Quantitation of Ia and CALLA antigens on HOON and HYON cell lines using a cellular radioimmunoassay revealed that both cells bind high levels of anti-Ia antibodies, 110 X 10(4) molecules per cell, and low levels of anti-CALLA antibodies, 7 X 10(4) molecules per cell. Although both HOON and HYON carry equivalent amounts of Ia on their surface, only the former is a good stimulator of the one-way mixed lymphocyte reaction.

Features and outcome of advanced neuroblastoma with distant lymph node metastasis.

We examined 52 children with advanced neuroblastoma who were diagnosed and treated during the past 7 years, and investigated the correlation between the degree of lymph node (LN) metastasis and the prognosis of neuroblastoma. In 8 of the 52 patients, distant LN metastasis was confirmed both radiographically and histologically. The urinary homovanillic acid (HVA) level was markedly elevated in these patients, and it was higher than that in patients with regional LN metastasis (p less than .05). The urinary vanillylmandelic acid (VMA) level and the VMA/HVA ratio were not significantly different between patients with regional and distant LN metastasis. None of the four examined patients with distant LN metastasis showed N-myc amplification of neuroblastoma tumors. An analysis of the survival rate in each patient group classified according to the degree of LN metastasis showed that the prognosis of the patients without LN metastasis or with distant LN metastasis tended to be better than that of patients with regional LN metastasis. Our results indicate that patients with distant LN metastasis may belong to a subclass with different biological features and a better prognosis than those of other groups.

Virus-associated haemophagocytic syndrome with Epstein-Barr virus infection

The clinical and histological findings of a 10-year-old girl with virus-associated haemophagocytic syndrome are presented. The serum levels of Epstein-Barr viral antigens were elevated. Epstein-Barr virus (EBV) genome was detected by polymerase chain reaction in bone marrow and lymph node specimens. Histologically, haemophagocytic histiocytes were present in bone marrow, and areas of non-suppurative necrosis were present in lymph nodes, where silver grain deposition of the EBV genome was demonstrated by in situ hybridization.

Treatment of Langerhans cell histiocytosis in children with etoposide.

Ten children with Langerhans cell histiocytosis (LCH) were treated with etoposide. For five patients, this was the initial diagnosis. The other five had failed to respond to previous therapies. Etoposide (100 mg/m2) was given intravenously twice a week for 4 weeks, followed by maintenance therapy every 2 to 4 weeks for 2 years. All 10 patients responded to etoposide, and 6 of them (60%) have been in complete remission for 3 to 36 months without any side effects. One patient relapsed with diabetes insipidus, one with a soft tissue mass, and two others developed multiple bone lesions. Chemotherapy with etoposide appears to be effective and safe for the treatment of children with systemic LCH.