pentostatin and Liver-Neoplasms

Hepatosplenic T-cell lymphoma (HSTL) is a rare and aggressive extranodal lymphoma derived mostly from cytotoxic γδ T-cells. The peak incidence is in adolescents and young adults, and is more common in males. Up to 20% of HSTL arise in the setting of chronic immune suppression, most commonly solid organ transplantation or prolonged antigenic stimulation. Patients present with systemic symptoms (fever), abdominal pain, weakness, and marked hepatosplenomegaly in the absence of lymphadenopathy. Patients usually manifest marked thrombocytopenia, often with anaemia and leucopenia, a leukemic phase, and bone marrow involvement in 80% of cases. Lactate dehydrogenase levels are usually markedly elevated. HSTL exhibits a marked chemoresistance to currently used regimens, a rapidly progressive behavior, and dismal prognosis. Patients with post-transplant HSTL exhibit an especially poor outcome. Standard treatment has yet to be established. Anthracycline-based chemotherapy is associated with a satisfactory response in two thirds of patients, but poor long-term results. Complete remission is extremely uncommon, and most patients die from lymphoma within two years of diagnosis. A prognostic correlation between outcome and degree of thrombocytopenia has been reported. Relapsing disease is usually chemorefractory and fast growing, and patients' performance status and clinical conditions are poor. These aspects, as well as the lack of drugs with proven activity against HSTL, render salvage treatment almost impossible. A few cases of HSTL successfully treated with autologous or allogeneic stem-cell transplantation have been reported. The use of 2'-deoxycoformycin and other targeted therapies, such as alemtuzumab, anti-γδ TCR monoclonal antibodies, and anti-CD44 therapy, have shown promising results in anecdotal reports.

Topics: Alemtuzumab; Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Liver Neoplasms; Lymphocytes; Lymphoma, T-Cell; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms

Hepatosplenic T cell lymphoma (HSTL) is a rare condition usually with an aggressive course and a poor prognosis even after extensive treatment. We describe here a patient who presented with hemophagocytosis. The lymphoma had unusual phenotypic features, an indolent course and responded to 20-deoxycoformycin therapy as a single agent. We suggest that this therapy be used in further cases as part of the treatment strategy.

Topics: Antineoplastic Agents; Female; Humans; Liver Neoplasms; Lymphoma, T-Cell; Middle Aged; Pentostatin; Remission Induction; Splenic Neoplasms

We report the results of treatment with single agent 2'-deoxycoformycin (Pentostatin) in two patients with Hepatosplenic gammadelta T-cell lymphoma (HSgammadeltaTCL), a rare lymphoma subtype with a highly unfavorable prognosis. Present and previous data reviewed here demonstrates the striking cytotoxic activity of Pentostatin against gammadelta+ tumor T cells. Further studies are warranted to define the optimal strategy to fully exploit therapeutic potential of this drug in patients with HSgammadeltaTCL.

Topics: Antineoplastic Agents; Humans; Liver Neoplasms; Lymphoma, T-Cell; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms

Topics: Adult; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Liver Neoplasms; Lymphoma, T-Cell; Male; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms

Topics: Adult; Bone Marrow Cells; CD3 Complex; Flow Cytometry; Humans; Immunohistochemistry; Immunosuppressive Agents; Leukocyte Common Antigens; Liver Neoplasms; Lymphoma, T-Cell; Male; Pentostatin; Receptors, Antigen, T-Cell; Splenic Neoplasms; T-Lymphocytes

We describe a patient with unusually indolent hepatosplenic gammadelta T cell lymphoma characterised by severe lassitude and high fever. No significant responses were obtained to a range of chemotherapeutic and biological agents. 2'-deoxycoformycin (dCF), however, produced a dramatic and sustained clinical and histological response. This is the second recent report of gammadelta T cell lymphoma responding to dCF, suggesting this agent may have a specific role in this condition.

Topics: Adult; Antibiotics, Antineoplastic; Female; Humans; Liver Neoplasms; Lymphoma, T-Cell; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Remission Induction; Splenic Neoplasms

Hepatosplenic gammadelta+ T-cell lymphoma represents a rare neoplasm of post-thymic phenotype, characterized by an aggressive clinical course and a poor response to conventional chemotherapy. In the present study, we have examined the cytotoxic effects of the purine analogue 2'-deoxycoformycin (dCF) on cultured mononuclear cells and purified gammadelta+ tumour cells from bone marrow or peripheral blood of four patients with hepatosplenic gammadelta+ T-cell lymphoma. At a concentration of 10 microM, dCF, in the presence of 2'-deoxyadenosine (dAdo), displayed an early and selective cytotoxic effect on gammadelta+ tumour T cells. After 48 h of in vitro exposure to dCF, the absolute number of viable CD3+/gammadelta+ tumour T cells was reduced by more than 90% in all samples with respect to control cultures, with absolute counts of viable CD3+/alphabeta+ lymphocytes being reduced only by 6-40% of the initial cell input. Analysis of cultures after 5 d of exposure to dCF plus dAdo revealed the persistence of normal CD3+/alphabeta+ T cells, which accounted, however, for only 20-25% of the initial cell input. Accordingly, the combination of dCF (10-100 microM) plus dAdo was able to induce a dose-dependent inhibition of clonogenic growth and [3H]-thymidine incorporation in purified CD3+/CD4-/CD8- gammadelta+ tumour cells. We also report that one patient with hepatosplenic gammadelta+ T-cell lymphoma in terminal leukaemic phase showed a striking haematological response to single-agent dCF given as fourth-line treatment. In particular, the selective clearance of gammadelta+ tumour T cells in peripheral blood and bone marrow was observed starting after the second course of treatment. Our results suggest that dCF may represent a potentially active drug for the management of this aggressive form of T-cell lymphoma.

Topics: Adenosine Deaminase Inhibitors; Adult; Enzyme Inhibitors; Female; Flow Cytometry; Humans; Immunophenotyping; Liver Neoplasms; Lymphoma, T-Cell; Male; Middle Aged; Pentostatin; Receptors, Antigen, T-Cell, gamma-delta; Splenic Neoplasms; Tumor Cells, Cultured