Yoshiko Ikuno

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.

Renin-producing hepatoblastoma.

Renin-producing tumors of extrarenal origin are rare in children. An 8-year-old boy with hepatoblastoma and hypertension associated with a high plasma renin level is reported. After chemotherapy, the plasma renin level normalized and the hypertension spontaneously resolved. The patient underwent surgery, and a right trisegmentectomy of the liver and a partial resection of the second and third segments were performed. The tumor was as shown the source of renin by immunohistochemical study and reverse transcriptase-polymerase chain reaction.

TREATMENT OF STANDARD-RISK ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN: The Results of Protocol AL841 from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan

A total of 62 patients with standard-risk acute lymphoblastic leukemia received three-drug induction consisting of vincristine, prednisolone, and L-asparaginase (l-Asp) followed by consolidation therapy with intermediate-dose methotrexate (MTX), intrathecal MTX, and 18 Gy of cranial irradiation. Maintenance therapy consisting of 6 drugs including daunorubicin (DNR, 450 mg/m2 in total) was continued for 3 years. Patients were randomized and half of them received weekly l-Asp during maintenance therapy as a late intensification. Complete remission (CR) was achieved in 61/62 (98.4%), and 11 of 61 patients relapsed. At 10 years, the event-free survival (EFS) was 80.6 +/- 5.0% and overall survival was 88.7 +/- 4.0%; median follow-up time was 9.3 years. The 10-year EFS of patients with additional l-Asp (84.8 +/- 6.2%) was superior to that without l-Asp (75.9 +/- 7.9%), although it was not statistically significant. No patients who received a full dose of DNR and maintained CR developed heart failure, although the shortening fraction decreased from 41.0% at diagnosis to 35.2% (median). The protocol AL841 provided good long-term disease control without severe late cardiac dysfunction.

Meningeal Neuroblastoma After Completing Therapy

Neuroblastoma is a common childhood malignant tumor having a very poor prognosis because of its very invasive characteristics. However, the central nervous system (CNS) is usually not affected, with the exception of the disseminating stage. A case with a mediastinal neuroblastoma having a solitary relapse in the CNS after completing therapy is reported here. A lumbar puncture revealed neuroblastoma cell clumps in the cerebrospinal fluid (CSF). This is a rare condition referred to as “meningeal neuroblastoma,” and aggressive therapy, including the intrathecal administration of nimustine (ACNU), was effective in removing the clump from the CSF.

Superoxide generation of leukemic cells in children

Superoxide (O2-) generation of leukemic cells was investigated in 28 children with acute leukemia. Leukemic cells of seven with acute myelomonocytic leukemia and one with acute monocytic leukemia produced various amounts of O2- (0.13-0.87 nmol/min/10(6) cells) when stimulated with wheat germ agglutinin (WGA) and phorbol myristate acetate (PMA). Other types of leukemia cells exhibited no such functions. Leukemic cells of two patients diagnosed as unusual cases of acute lymphoblastic leukemia generated significant amounts of O2- when stimulated with WGA and PMA. Both patients went into complete remission while on acute nonlymphoblastic leukemia treatment. Thus O2- generating activity can serve as a functional marker of leukemic cells in myelomonocytic lineage.

TREATMENT OF CHILDHOOD ACUTE MYELOGENOUS LEUKEMIA WITH ALLOGENEIC AND AUTOLOGOUS STEM CELL TRANSPLANTATION DURING THE FIRST REMISSION: A Report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan

A total of 64 newly diagnosed acute myelogenous leukemia patients (except FAB M3 and/or Down syndrome) under 18 years of age were consecutively enrolled into the study. Patients having an HLA-identical sibling (allo group) were assigned to undergo allogeneic bone marrow transplantation (allo BMT) in the first complete remission (CR). Others (non-allo group) were assigned to undergo autologous peripheral blood stem cell transplantation (PBSCT) or autologous BMT (auto BMT). Conditioning regimen was busulfan + melphalan for all transplantation. Of 64 patients (allo group 24; non-allo group 40), 59 (92.2%) achieved a CR. Eighteen relapses occurred (allo group 4; non-allo group 14) and 6 died during the first CR. The 5-year event-free survival (EFS) rate was 53.3 +/- 6.4% at a median follow-up period of 45 months. The 5-year EFS rates of allo and non-allo groups were 70.8 +/- 9.3% and 43.0 +/- 8.1%, respectively (p = .08). The EFS rates at 5 years post-transplant for allo BMT from an HLA-identical sibling (n = 18), PBSCT (11), and auto BMT (6) were 88.1 +/- 7.9%, 41.6 +/- 19.7%, and 83.3 +/- 15.2%, respectively. The outcome of allo BMT was superior to that of autograft. Auto BMT rather than PBSCT might contribute to a long-term survival in case of no available HLA-identical siblings.

An Adolescent Case of Retroperitoneal Pure Choriocarcinoma: Successful Treatment with MCNU-Containing High-Dose Chemotherapy Followed by Autologous Bone Marrow Transplantation after Multiple Brain Metastases

Choriocarcinoma is a rare disease in pediatric neoplasms. The prognosis of the disease is extremely poor once when patients relapse or become refractory to cisplatin (CDDP). A 17-year-old male who had retroperitoneal pure choriocarcinoma of advanced stage was treated with CDDP-based intensive chemotherapy. In spite of the initial good response to CDDP-based intensive chemotherapy, the tumor metastasized to multiple areas of the brain during chemotherapy. Since the brain in this case was thought to be a sanctuary, after radiotherapy to the whole cranium, the patient was treated with high-dose chemotherapy consisting of etoposide, carboplatin, and ranimustine (MCNU), which can penetrate the blood-brain barrier, followed by autologous bone marrow transplantation (ABMT). Twenty-four months after ABMT, the patient had no sign of disease recurrence. MCNU-containing high-dose chemotherapy with ABMT appears to be quite effective in cases that present with relapsing multiple brain metastases during CDDP-based chemotherapy.

An effective salvage regimen with aclarubicin for daunorubicin-resistant acute non-lymphocytic leukemia in children

We evaluated the efficacy and toxicity of aclarubicin for acute non-lymphocytic leukemia (ANLL) refractory to daunorubicin in childhood. Twenty-four patients were treated with aclarubicin and prednisolone with or without 6-mercaptopurine and behenoyl-cytosine arabinoside daily for 5 to 14 days. Of 21 evaluable patients, 14 (67%) responded: 12 obtained complete remission and 2 partial remission. The median time to reach complete remission was 37 days (range, 16 to 60 days), and the median duration of complete remission was 5.5 months (range, 2 to 41 months). The cumulative dose of anthracycline administered before the study was not considered significant for the response. The only major complication was severe bone marrow suppression; infectious episodes occurred in 14 patients (58%) and three died of sepsis and/or bleeding. The observed non-hematologic toxicities included hematuria, an elevation of serum amylase, nausea/vomiting, and angitis. In addition, one patient showed abnormal cardiac function. Aclarubicin is therefore considered a highly active drug for remission reinduction of previously treated children suffering from ANLL with an acceptable toxicity.

Natural Killer Cell Activity in Children With Acute Lymphoblastic Leukemia

Thirty‐four children with acute lymphoblastic leukemia (ALL) and 45 normal children as controls were tested for natural killer (NK) cell activity in vitro using the K‐562 cell line as target cell.