9 Mice were injected i.p. model for the study of the biology and design of treatment Fumalic acid (Ferulic acid) modalities for CD30+ ALCL. Anaplastic large cell lymphoma LFA3 antibody (ALCL) was first Fumalic acid (Ferulic acid) described in 1985 as a CD30+ large cell lymphoma with distinctive anaplastic cell morphology, characteristically infiltrating the paracortical region and sinuses of lymph nodes. 1 It was subsequently shown that this tumor affects primarily children and is associated with frequent extranodal disease, especially skin involvement. 2 There is a recurrent translocation, t(2;5)(p23;q35), resulting in the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to a novel tyrosine kinase-encoding gene designated anaplastic lymphoma kinase (ALK) on chromosome 2p23 observed in 30 to 70% of all ALCLs. 3-7 Although patients whose tumors express the NPM-ALK protein have a statistically better prognosis, some children with NPM-ALK-positive tumors have disease resistant to multiple chemotherapy regimens. According to a recent study conducted by Childrens Cancer Group, pediatric patients with systemic ALCL have only a 41% five year disease-free survival and a 62% overall five year survival (MEK, personal communication). Thus novel therapies for treatment resistant ALCL are needed. To address this issue, we developed a xenograft model of treatment resistant ALCL. SCID/bg mice were chosen for this purpose because they have impairment of natural killer cell activity in addition to the lack of B and Fumalic acid (Ferulic acid) T cell function. The model was found to closely resemble the primary tumor in histopathology and in clinical behavior with widespread organ involvement. The transcription of NPM-ALK and of various cytokines which could explain the Fumalic acid (Ferulic acid) patients symptoms was demonstrated. Finally, the model was used to test the efficacy of immunotherapy directed against the CD30 antigen expressed by the tumor cells. Materials and Methods Patient The patient is a 22-month-old Caucasian female who presented with 2-month history of fever, cervical adenopathy, and weight loss. The diagnosis was at first difficult to establish because of the admixture of small and large atypical cells. Over the next 2 months the patient developed progressive lymphadenopathy. CAT scans revealed supraclavicular nodes extending into the mediastinum and enlarged paratracheal, axillary, subcarinal, and periaortic lymph nodes. A pleural effusion contained small, CD30+, cytologically malignant cells, with frequent mitoses. Cytogenetics revealed a t(2;5)(p23;q35) translocation. Bone marrow aspirate showed 7% malignant cells. Cerebrospinal fluid was negative for tumor cells. The patient was treated with adriamycin, prednisone, and vincristine. She tolerated the first course of chemotherapy well, and a CAT scan on day 30 showed persistent matted nodes in the supraclavicular region and a persistent mass in the anterior mediastinum. Biopsy of the mediastinum was interpreted as scar tissue. Five days later the patient developed fever and gum swelling. Biopsy of the gum showed recurrent lymphoma. She developed rapidly increasing cervical adenopathy. High-dose etoposide and cyclophosphamide were administered but complicated by enteritis. CAT scan showed partial response, and a second round of chemotherapy was administered. Subsequent CAT scan showed tumor reduction, but before the next cycle of chemotherapy she developed fever and rapidly progressive bilateral cervical adenopathy. Two cycles of steroids, high-dose Ara-C, and cisplatin (DHAP) achieved a good clinical response. The patient is currently completing bone marrow transplantation from a matched unrelated donor. Tumor Cell Preparation A peripheral blood sample containing circulating tumor cells was obtained with informed consent from the patient at the time of the diagnosis. Peripheral blood mononuclear cells were isolated by gradient centrifugation using Ficoll Paque Plus (Pharmacia Biotech, Uppsala, Sweden), washed twice in PBS and resuspended in RPMI 1640 (BioWhittaker, Walkersville, MD). Animals Four to six-week-old SCID/bg mice were obtained from Taconic Farms (Germantown, NY) and housed in autoclaved microisolator cages in an air-filtered laminar flow cabinet within the Animal Research Facility of the Beth Israel Deaconess Medical Center. Food was irradiated, and water and bedding were autoclaved before use. All.