Correspondence

Relapsing Lymphoma

N Engl J Med 1995; 333:194-195July 20, 1995

Article

To the Editor:

The report by Kaufmann et al. (Feb. 23 issue)1 on the remarkable clinical course of a patient with mantle-cell lymphoma offered an ingenious explanation for the recurrent spontaneous remissions they observed. However, their demonstration of apoptosis in circulating lymphoma cells during the early phase of the remissions leaves unanswered the question whether the trigger mechanism was intrinsic or extrinsic to the tumor cells. We suggest that an undulating T-cell–mediated immune response against lymphoma cells may have been involved. We analyzed a similar case in which a patient with anaplastic large-cell lymphoma had repeated spontaneous remissions. We found histologic and immunologic evidence of a T-cell–mediated antilymphoma immune reaction.

The observations of Kaufmann et al. are consistent with the occurrence of waves of an antilymphoma immune attack that were only partially and temporarily successful. The fact that atypical lymphocytes (activated T lymphocytes?) were seen in the peripheral blood during the early phases of remission fits this hypothesis. Induction of apoptosis is a key effector mechanism of T-cell–mediated target-cell killing,2 and theory predicts that cycling is a possible response of the immune system.3 Although admittedly rare, spontaneous remissions deserve to be considered as part of T-cell–mediated immune mechanisms, particularly because patients in whom this phenomenon occurs may be candidates for treatment with low-dose recombinant interleukin-2.4,5

Gideon D.M. Beun, M.D., Ph.D.
University Medical Center, 2333 AA Leiden, the Netherlands

Lodewijk T. Vlasveld, M.D., Ph.D.
Diaconessenhuis, 5631 BM Eindhoven, the Netherlands

Mars B. van 't Veer, M.D., Ph.D.
Dr. Daniel den Hoed Cancer Center, 3008 AE Rotterdam, the Netherlands

5 References

1. 1

   Kaufmann Y, Many A, Rechavi G, et al. Lymphoma with recurrent cycles of spontaneous remission and relapse -- possible role of apoptosis. N Engl J Med 1995;332:507-510
   Full Text | Web of Science | Medline

2. 2

   Zychlinsky A, Zheng LM, Liu CC, Young JD. Cytolytic lymphocytes induce both apoptosis and necrosis in target cells. J Immunol 1991;146:393-400
   Web of Science | Medline

3. 3

   Segel LA, Jager E, Elias D, Cohen IR. A quantitative model of autoimmune disease and T-cell vaccination: does more mean less? Immunol Today 1995;16:80-84
   CrossRef | Medline

4. 4

   Vlasveld LT, Rankin EM. Recombinant interleukin-2 in cancer: basic and clinical aspects. Cancer Treat Rev 1994;20:275-311
   CrossRef | Web of Science | Medline

5. 5

   Beun GD, van de Velde CJ, Fleuren GJ. T-cell based cancer immunotherapy: direct or redirected tumor-cell recognition? Immunol Today 1994;15:11-15
   CrossRef | Medline

Author/Editor Response

The authors reply:

To the Editor: We thank Dr. Beun and his colleagues for informing us of an additional case of lymphoma with a cyclic pattern. Beun et al. suggest that the action of cytotoxic T lymphocytes against the lymphoma cells may have caused the repeated remissions. We have examined this possibility and were unable to detect in the patient's peripheral blood any cytotoxic-T-lymphocyte activity against the autologous lymphoma cells at any phase of the disease (unpublished data).

Beun et al. suggest treatment with low-dose interleukin-2 for patients with lymphoma who have spontaneous remissions. We do not think that this would be adequate for our patient. His lymphoma cells express surface receptors for interleukin-2 and have a low proliferative response to interleukin-2 that is potentiated by other cytokines (unpublished data). These in vitro results would contraindicate therapy with interleukin-2, which might increase the patient's malignant clones in vivo. In contrast, prednisone enhances apoptosis of the lymphoma cells in culture, and treatment of the patient with low doses of prednisone has been very effective. During the past 18 months the patient has had seven cycles of relapse and remission (cycles 11 through 17). During each relapse he was treated initially with 25 mg of prednisone per day, and the dose was subsequently tapered over a period of several weeks. With this treatment the attacks were short and very mild, lasting two to three days, with hardly any lymphadenopathy or hepatosplenomegaly.

Yael Kaufmann, Ph.D.
Amira Many, M.D.
Bracha Ramot, M.D.
Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel