A new approach for eradication of residual lymphoma cells by host nonreactive anti–third-party central memory CD8 T cells

Key Points Anti–third-party Tcm kill malignant B cells in a T-cell receptor–independent mechanism while sparing naive B cells.

Treatment of Diffuse Large B-Cell Lymphoma of the Liver with Yttrium-90 Microsphere Embolization.

We present a case of successful treatment of chemoresistant hepatic lymphoma using yttrium-90 micropheres. A 41 year-old male with a history of hepatitis C presented with fatigue, night sweats, right upper quadrant pain, a 20 pound weight loss, and hypercalcemia. CT scan of the abdomen revealed a 13.4 x 10.0 cm mass involving the right hepatic lobe, along with portohepatic, celiac, and retroperitoneal lymphadenopathy. Ultrasound-guided core biopsy of the portohepatic mass showed diffuse large B-cell lymphoma (DLBCL). The patient had a partial response to R-CHOP, and was subsequently treated with 3 additional chemotherapeutic regimens. Despite this extensive therapy, as well as surgical resection of hepatic lesions, he had residual lymphoma within the liver. Due to inadequate chemosensitivity, he was not a candidate for stem cell transplantation. Repeat biopsy showed loss of CD20 expression, eliminating radioimmunotherapy as an option. Because the residual lymphoma was confined to the liver, the patient was treated with yttrium-90 microspheres (TheraSphere®). The patient had a significant improvement in his abdominal pain. Furthermore, six weeks after treatment, a complete response in the hepatic lesions was documented by PET/CT scan. Although the patient later developed recurrent disease outside of the liver, the case clearly demonstrates the potential clinical utility of this approach in properly selected lymphoma patients. To our knowledge, this is the first reported case documenting clinical activity of yttrium-90 microspheres for lymphoma.

Anti-Idiotype Antibodies Can Induce Long-Term Complete Remissions in Non-Hodgkin’s Lymphoma Without Eradicating the Malignant Clone

The immunoglobulin on the surface of B-cell lymphomas can be a tumor-specific target for monoclonal antibody therapy. Between 1981 and 1993, 45 individuals with low grade B-cell lymphoma were treated with 52 courses of custom-made anti-idiotype antibodies. The antibodies were used either alone or in combination with -interferon, chlorambucil, or interleukin-2 (IL-2). The majority of these patients responded to treatment, with a 66% overall and 18% complete response rate. Six patients (13%) experienced prolonged complete remissions, five of which are ongoing from 4 to 10 years after therapy and are the subject of this report. We asked whether residual lymphoma could be found in these patients with prolonged remissions. We performed enzyme-linked immunosorbent assay (ELISA) assays for idiotype protein or anti-idiotype antibodies in serum. Blood and bone marrow samples were examined by flow cytometry for idiotype positive cells, and by polymerase chain reaction (PCR) for clonal gene rearrangements of immunoglobulin CDR3 sequences or t(14;18) translocations. Using these sensitive and specific tests it was possible to detect very low levels of residual lymphoma in five of these patients who had been in clinical remission for 3 to 8 years before this evaluation. These five have continued without recurrence for up to 3 years since. Thus, we have found a pattern of residual inactive disease in patients treated with anti-idiotype antibodies. The biology of follicular lymphoma evidently includes the potential for tumor dormancy after therapies with varied mechanisms of action, resulting in clinical inactivity for many years. Thus, long-term control of the disease is possible at a clinical level despite persistence of the malignant clone. © 1998 by The American Society of Hematology.