Pediatric Oncology Division

Introduction
The Pediatric Oncology Division handles a wide variety of malignancies in children and adolescents. The pediatric ward (12A) is admitting more than 130 patients per year, who are referred from hospitals located throughout Japan and other Asian countries, including Taiwan, Korea, and so forth. The diseases we treat include both hematological malignancies such as acute leukemias and malignant lymphomas, and solid tumors such as soft tissue sarcomas, neuro-blastoma, Wilms tumor and retinoblastoma.
Based on the heterogeneity of the disease-spectrum, we have built up a multidisciplinary network with other divisions, such as surgery (including orthopedic surgery, neurosurgery, urology, and ophthalmology), radiation oncology, and hematopoietic stem cell transplantation (SCT). Although SCT procedure is usually performed in the transplantation ward (12B), the 12A ward also accepts patients undergoing autologous SCT.
A special nursing care system in the ward helps young patients and families both physically and psychologically. They provide appropriate information to help patients and families to keep their ideal relationship. To elevate the quality of hospital life of young patients, an educational opportunities ranging from elementary school to a high school are available in the pediatric ward, where 9 teachers work daily. For inpatients families who come from distant areas, the Family Houses are available with affordable accommodation fees in several areas in Tokyo.

Routine Activities
The division has two staff pediatricians, and several trainees. The pediatric outpatient service opens every morning to treat new patients and provide follow-up treatment to patients who have completed intensive treatment course. The pediatric staffs and trainees discuss various issues in pediatric inpatients on round on a daily basis. Patients undergo various procedures in a timely manner, sometimes under IV sedation. These procedures include diagnostic bone marrow aspiration/biopsy, central venous catheter placement, and lumbar puncture/ intrathecal chemotherapy. The Pediatric Conference is held in Wednesday afternoon mainly for the decision-making of individual treatment plan. The pediatric staffs also join in the Transplant Conferences on Monday, Wednesday and Friday and the Orthopedic Surgery Conference on Tuesday. There are several academic meetings for educational purpose, they are the Hemato-oncology Journal Club on Tuesday morning and SCT-Case Discussion in English on Wednesday evening.
The common approach to the diseases is risk-adapted therapy regarding the long-term life-expectancy. Patients with solid tumors receive multidisciplinary therapy, including surgical removal of the tumor, radiation therapy, chemotherapy, and sometimes SCT as indicated. Patients with hemato-logical malignancies usually receive induction or re-induction chemotherapy first. Then, they are assigned either to chemotherapy course or SCT course based on the risk of the disease. Since the main reason of referral of the patients is the refractoriness of the diseases to conventional therapies, many of the patients are treated with SCT in either autologous or allogeneic settings.

Research Activities
I. New treatment strategy for refractory solid tumors in children and young adults
(1) Double autologous SCT following high-dose chemotherapy.
(2) This strategy had been applied to a total of 2 pediatric patients with Ewing sarcoma. Both patients succeeded in tandem transplant without serious toxicity.
(2) Nonmyeloablative/reduced intensity SCT (Mini-SCT)
The objective of this study is to evaluate safety and efficacy of mini-SCT on refractory solid tumors with an expectation of immunological eradication of residual tumors by allografts (graft-versus-tumor effect). This collaborative study with the SCT division is ongoing and results of interim analysis were presented at ASCO 2001 (Makimoto et al.).
II. Cord blood transplantation (CBT) for high- risk hematologic malignancies
Cord blood (CB) is the third alternative source of stem cell graft in a transplant setting. Relatively low immnogenicity of CB enables patients to receive mismatched graft (Ohnuma K, Ohira M, et al.). In 2001, a total of 2 pediatric patients with AML received CBT.
III. Establishment of ideal treatment strategy for patients with retinoblastoma (RB)
In 2001, a total of six patients with advanced retinoblastoma received multi-agent chemotherapy. Two patients
received autologous SCT. In order to facilitate the strategy in local ophthalmic therapies (LOT), we need to develop strong salvage therapies for patients who relapsed on or after the LOT. We are pursuing a risk-adapted treatment strategy for RB patients with good QOL, based on the retrospective data of risk factors (Higa et al).

Clinical Trials
Since December 2001 when we held a meeting for the purpose of reconsidering about multi-center clinical studies in pediatric oncology in Japan, the new movement occurred to pursue the ideal, GCP-based clinical studies. In this movement, we are leading the activity to make several new clinical protocols and a new pediatric data-center. Opinions and discussions are being accumulated on the mailing lists. Currently, five protocols, including Phase III open randomized control trial to compare bone marrow and blood stem cell as an allogeneic graft for treatment of leukemia, are discussed and under development.
(1)We expect that the new protocols will replace old-fashioned ones eventually. However, it will take at least two or three years to complete this transient confusion. In the meanwhile, the clinical trials mainly for hematological malignancies are still open by the Tokyo Childrens Cancer Study Group.

A. MAKIMOTO
M. OHIRA

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