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Keywords:

  • hepatosplenic;
  • γδ T-cell lymphoma;
  • pentostatin

Hepatosplenic γδ T-cell lymphoma (HSγδTCL) is a rare but distinct entity (Farcet et al, 1990), which mainly affects young males and is characterized by hepatosplenomegaly but no or little lymphoadenopathy, frequent B symptoms, thrombocytopenia and poor response to conventional chemotherapy (Wong et al, 1995). A wide and heterogeneous array of therapies has been applied: monotherapy with steroids or alkylating agent, fludarabine, splenectomy, polychemotherapy and bone marrow transplantation. Despite different therapeutic approaches, complete remission (CR) is rarely obtained and the few responding patients relapse early with virtually all patients dying within 2 years (Weidmann, 2000). Pentostatine is a potent inhibitor of adenosine deaminase with a marked cytotoxic activity on T lymphocytes and has been shown to be effective in treatment of some histotypes of T-cell lymphomas (Kurzrock, 2000). Recent evidence displayed sensitivity of γδ cells to pentostatine in vitro (Aldinucci et al, 2000) and prompted us to treat a patient affected with HSγδTSL using this drug.

In April 1999, a 42-year-old Caucasian man was admitted to our ward because of night sweats, weight loss, dull pain at left ipocondrium, mild anaemia and thrombocytopenia discovered 2 weeks previously. Physical examination highlighted massive splenomegaly (20 cm below left costal margin) and hepatomegaly (7 cm below costal margin at midclavicular line). Haematological and biochemical tests revealed mild normochromic anaemia (Hb 10 g/dl) and thrombocytopenia (60 × 109/l), severe neutropenia and lymphocytopenia (white blood cells, 1·1 × 109/l; neutrophils, 0·4 × 109/l; lymphocytes, 0·6 × 109/l). Lactate dehydrogenase and beta2 microglobulin were within normal range. Virological tests documented an acquired immunity for hepatitis B virus and Epstein–Barr virus, and were negative for hepatitis C virus and human immunodeficiency virus infection. Bone marrow aspiration showed a 40% infiltrate consisting of medium-sized lymphocytes with slightly indented nuclei, small nucleolus and a small rim of lightly basophilic cytoplasm; the immunophenotype was as follows: CD3+, CD2+, CD8+, CD4, CD5, CD10, CD56/16+, TCR αβ, TCR γδ1+.

A bone marrow trephine biopsy demonstrated a characteristic exclusively intrasinusoidal infiltrate consisting of medium-sized T lymphocytes (immunohistochemistry ABC Strept LCA+, CD20, CD45RO+, CD45RA).

The diagnosis of HSγδTSL was made and the patient was treated with pentostatin (4 mg/m2 intravenously every 2 weeks for 6 months). The disappearance of B symptoms and shrinkage of the spleen rapidly followed the first administration of pentostatin. At restaging, performed after 10 courses of pentostatin, the patient was found to be in complete remission (neither lymph nodes nor liver or spleen enlargement were detected using a computerized tomography scan and the bone marrow infiltrate was completely clear). There was no significant treatment-related toxicity. The patient received another two monthly courses of pentostatin and subsequently underwent a successful mobilization of peripheral blood stem cells (PBSC) using cyclophosphamide 7 g/m2 plus granulocyte colony-stimulating factor (10 µg/kg/d) with a yield of 6·5 × 106/kg CD34+. In January 2000, high-dose therapy was administered with idarubicin (21 mg/m2, d −9 to d 8 and melphalan 140 mg/m2, d −3) followed by reinfusion of the PBSC. Twelve months after transplant the patient is well and still in CR.

In conclusion, the case reported here, which showed an impressive responsiveness to pentostatin, suggests that this purine nucleoside analogue can obtain a CR with negligible toxicity. Moreover, pretreatment with pentostatin did not impair the collection of PBSC with the schedule used in this patient. To the best of our knowledge this is the first case treated successfully with pentostatin. We think that it could be reasonable to consider therapy with pentostatin as a possible option for induction therapy of patients affected by HSγδTCL.

References

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  2. References
  • Aldinucci, D., Poletto, D., Zagonel, V., Rupolo, M., Degan, M., Nanni, P., Gattei, V. & Pinto, A. (2000) In vitro and in vivo effects of 2′-deoxycoformycin (Pentostatin) on tumour cells from human gammadelta+ T-cell malignancies. British Journal of Haematology, 110, 188196.DOI: 10.1046/j.1365-2141.2000.02129.x
  • Farcet, J.P., Gaulard, P., Marolleau, J.P., Le Couedic, J.P., Henni, T., Gourdin, M.F., Divine, M., Haioun, C., Zafrani, S., Goussens, M., Hercend, T. & Reyes, F. (1990) Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta. Blood, 75, 22132219.
  • Kurzrock, R. (2000) Pentostatin (Nipent) in T-cell lymphomas. Seminars in Oncology, 27, 6466.
  • Weidmann, E. (2000) Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990. Leukemia, 14, 991997.
  • Wong, K.F., Chan, J.K., Matutes, E., McCarthy, K., Ng, C.S., Chan, C.H. & Ma, S.K. (1995) Hepatosplenic gamma delta T-cell lymphoma. American Journal of Surgical Pathology, 19, 718726.