Hematopoietic Stem Cell Transplantation Team

Introduction
Hematopoietic stem cell (HSC) transplantation activity at the National Cancer Center Hospital has been focused on the establishment of comprehensive cell therapy program. Pediatric transplant program merged with the adult program to strengthen the transplant team. Twenty-six beds in the 12B and additional 3 beds on the 11A wards are solely dedicated to the Transplant Unit and air-handling on the unit is filtered by a central high-efficiency particulate air (HEPA) filtration system, which keeps NASA class 10,000 level sterility anywhere. In addition to ample cell processing facilities on the adjoining 12th floor, sterile cell processing resources also exists on the 11th floor where we perform cell processing of apheresis-collected cells for dendritic cell-based immuno-therapy in good manufacturing procedures (GMP).

Routine Activities
The transplant program was attended by Drs. Takaue, Mineishi, Tanosaki and Kami. Dr. Makimoto, from University of Texas M.D. Anderson Cancer Center, joined as a joint member with Pediatrics. In year 2001, a total of 107 transplantations were performed and a breakdown of transplants by type of stem cell source is summarized in the Table. Thus, this unit has become the largest one in the country. A residency-training program in the Transplant Unit was started in 1999, for which currently 10 residents have been enrolled.
The Unit is staffed by 25 nurses trained in oncology, HSC transplantation, and all aspects of critical care medicine needed to take care of these patients. With accumulating experience in allogeneic transplantation procedures, the nursing unit has been taking leadership in an effort to facilitate a simplification of sterile procedures and reduction of cost in patient care. An exchanging training program for nursing staff has been arranged with the Oncology Services, Nebraska Health System University of Nebraska Medical Center with support from the Foundation for Promotion of Cancer Research, Japan. They are dispatched to Omaha for 3 weeks.

Research Activities
The Transplant/Cell Processing Laboratory has major interest in cell processing, hematopoiesis, transplant immunology, lymphocyte biology and cytokine kinetics. The Laboratory provides all needed services for both autologous and allogeneic PBSCT or bone marrow transplantation, and five well-trained technologists provide technical support. The primary target of research in hematology/transplantation areas includes chimerism induction and immunological recovery process after transplantation. The major effort currently underway in cell-mediated immuno-therapy is to develop a unified battery of assays which would allow the quantitative description of the immunocompetent cell kinetics in cancer patients. A significant body of research exists in the affiliated National Cancer Research Institute in the immunology field with a number of investigators working in NKT cell or dendritic cell-based research. Our research activities are being made in collaboration with Dr. Wakasugi and Heike of the Pharmacology Division.

Clinical Trial
Recently, it has been shown that the anti-tumor activity of allogeneic transplantation is more related to the graft-versus-tumor (GVT) effect rather than the anti-tumor effect of the conditioning chemo-radiotherapy. Hence, total tumor eradication by high-dose therapy and/or total body irradiation is not mandatory. Nowadays the purpose of the conditioning regimen is considered to be more immunosuppression to ensure the engraftment of the donor cells which contain both HSC and lymphocytes, rather than the bone marrow ablation.
Hence, our transplant team is currently focusing on developing effective procedures for allogeneic cell therapy. Characteristics of current program are non-myeloablative ( mini ) transplantation with the use of less intensive cytoreductive regimen, which is particularly suitable for older patients and patients with significant underlying organ dysfunctions.We are now conduting a phase I/II study to establish a novel mini-transplantation regimen consisting of cladribine 0.11 mg/kg or fludarabine 30 mg/m2 on days -8 to -3, busulfan 4mg/kg/day on days -4 and -3, with or without rabbit anti-thymocyte globulin. Target patient population eligible for the study included those with hematological malignancies, who were older than 50 year old or who had organ dysfunction to prevent application of conventional transplantation procedure, or those with progressive solid tumors which were refractory to available conventional chemoradio-therapies. Primary end point of this study was early transplant-related mortality. Between July 1999 and December 2001, a total of 69 patients were enrolled.

Y. TAKAUE

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