1 Department of Immunology and Hematology, 2 Laboratory of Pathology, Hôpital Saint-Louis, AP-HP, Paris; 3 Department of Pediatric Hematology, Hôpital Armand Trousseau, AP-HP, Paris; 4 Department of Hematology, Centre Jean-Bernard, Le Mans, France (E-mail: emmanuelle.boulanger{at}sls.ap-hop-paris.fr)
Nodular lymphocyte-predominant Hodgkins disease (NLPHD) is a rare tumor distinct from classical Hodgkins disease and classified as a low-grade B-cell lymphoma with a nodular growth pattern. Rare lymphocytic and histiocytic (L&H) tumor cells are scattered in a lymphocyte-rich background. These cells have a CD30 CD15 EMA+ CD20+ phenotype. Transformation to high-grade non-Hodgkins lymphoma (NHL) is reported in <5% of cases. Most patients are diagnosed with early-stage disease. Less than 10% of patients have a stage IV disease. Liver, bone marrow and lung are the most frequently involved organs. Patients with advanced disease are treated with chemotherapy, and have a high risk of secondary neoplasms and treatment-related toxicities [1]. The slow disease progression and the CD20+ tumor cells prompted us to use the monoclonal antibody rituximab to treat a patient with a pulmonary stage IV NLPHD.
Case report
In 1985, a 16-year-old boy presented with splenomegaly and cervical lymphadenopathy that demonstrated NLPHD on biopsy. Observation without specific therapy was proposed. In 1994, the patient was admitted for increasing cervical lymphadenopathy. Abdominal echography showed nodular splenomegaly. Another cervical lymph node biopsy showed the same histological pattern of NLPHD. A wait and see policy was recommended again. In April 2000, he complained of cough and systemic symptoms. Cervical lymphadenopathy was unchanged. The hemoglobin level was 10.7 g/dl, leukocyte count was 0.9 x 109/l and platelets 107 x 109/l. Serum lactate dehydrogenase level was normal. Bone marrow aspiration and biopsy were normal. Computed tomography scan revealed heterogeneous splenomegaly and multiple pulmonary nodular lesions without mediastinal lymphadenopathy. Splenectomy was performed. The spleen weighed 1.5 kg and was infiltrated by large-size nodular areas containing numerous small lymphocytes of B phenotype surrounding few CD20+ CD30 CD15 L&H cells, consistent with a splenic localization of NLPHD without transformation. Because the patient refused conventional chemotherapy, he received four weekly intravenous infusions of 375 mg/m2 of rituximab. In September 2000, the pulmonary lesions and the cervical lymphadenopathy significantly decreased in size. In December 2000, recurrence of cough and B symptoms revealed progression of pulmonary nodules. A transparietal pulmonary biopsy did not show any specific lesion. The patient was then lost to follow-up.
In Annals of Oncology vol. 12, Kirchner et al. reported a complete remission (CR) after rituximab treatment of a transformation of NLPHD to high-grade large B-cell lymphoma with pulmonary specific involvement [2]. A sustained CR after rituximab had already been reported in two cases of relapsing and/or chemorefractory stage IV NLPHD without histological evidence of transformation [34]. One of these patients had pulmonary nodules [3]. Contrary to these cases, the rituximab failed to induce a CR in our patient. As all the published patients had disseminated and bulky disease, the minor effect of rituximab observed in our case could not be explained by the tumoral mass size or the extended stage. One mechanism of rituximab resistance may involve the expression of CD55 and/or CD59 inhibitors of complement-mediated lysis, as reported for follicular lymphoma [5]. A loss of CD20 expression by tumor cells is another possible explanation.
E. Boulanger1*, V. Meignin2, G. Leverger3 & P. Solal-Céligny4
1Department of Immunology and Hematology, 2Laboratory of Pathology, Hôpital Saint-Louis, AP-HP, Paris; 3Department of Pediatric Hematology, Hôpital Armand Trousseau, AP-HP, Paris; 4Department of Hematology, Centre Jean-Bernard, Le Mans, France (*E-mail: emmanuelle.boulanger{at}sls.ap-hop-paris.fr)
References
1. Diehl V, Sextro M, Franklin J et al. Clinical presentation, course and prognostic factors in lymphocyte-predominant Hodgkins disease and lymphocyte-rich classical Hodgkins disease: report from the European task force on lymphoma project on lymphocyte-predominant Hodgkins disease. J Clin Oncol 1999; 17: 776783.
2. Kirchner EM, Ebsen M, Kirchner J et al. Transformation of Hodgkins disease to high-grade B-cell lymphoma: remission after rituximab monotherapy. Ann Oncol 2001; 12: 11691171.[Abstract]
3. Keilholz U, Szelényi H, Siehl J et al. Rapid regression of chemotherapy refractory lymphocyte predominant Hodgkins disease after administration of rituximab (anti-CD20 monoclonal antibody) and interleukin-2. Leuk Lymphoma 1999; 35: 641642.[ISI][Medline]
4. Lush RJ, Jones SG, Haynes AP. Advanced-stage, chemorefractory lymphocyte-predominant Hodgkins disease: long-term follow-up of allografting and monoclonal antibody therapy. Br J Haematol 2001; 114: 734735.[ISI][Medline]
5. Golay J, Zaffaroni L, Vaccari T et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood 2000; 95: 39003908.