Chemotherapy-resistant intravascular lymphoma accompanied by ADAMTS13 inhibitor successfully treated with rituximab

Abstract

Intravascular large B-cell lymphoma (IVL) is a subtype of diffuse large B-cell lymphoma (DLBCL), in which lymphoma cells infiltrate blood vessels without mass formation, and its prognosis is generally poor due to diagnostic difficulties. The authors previously described a patient with IVL accompanied by features of thrombotic thrombocytopenic purpura (TTP), expression of ADAMTS13 inhibitor, and a severe deficiency in ADAMTS13 activity [1]. Although standard CHOP chemotherapy was initially effective, the disease gradually became resistant despite intensive high-dose chemotherapy with autologous peripheral blood stem cell support. However, the chimeric anti-CD20 monoclonal antibody, rituximab, induced complete remission (CR) for a prolonged period. We describe the clinical course of this patient and the unique effects of treatment with rituximab alone. A 54-year-old man was admitted to our hospital with the onset of a psychological disorder and convulsions. Laboratory data revealed obvious thrombocytopenia (3.6 9 10/ lL) accompanied by elevated levels of serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor. Multiple cerebral venous embolisms, bilateral adrenal gland swelling, and hepatosplenomegaly were present without nodal disease. Despite normal chest X-rays and thoracic CT scans, the patient developed rapidly progressive respiratory failure. A definitive diagnosis of IVL was made from transbronchial lung biopsy (TBLB) specimens. Bone marrow smears revealed no obvious lymphoma cell invasion and megakaryocyte hyperplasia without hemophagocytic syndrome (HPS), although the peripheral blood platelet count was markedly decreased. We concluded that the thrombocytopenia was caused by the same pathogenesis as TTP, since plasma ADAMTS13 activity had decreased to below 3%, and active ADAMTS13 inhibitor (IgG-type autoantibody) was confirmed. After standard CHOP chemotherapy cycles, the platelet counts immediately recovered to within normal limits and all symptoms improved. The ADAMTS13 activity improved to 49% and inhibitor levels, which had never been negative, decreased. Whole brain irradiation after chemotherapy resulted in relapse of systemic disease. Although we performed highdose conditioning chemotherapy followed by autologous peripheral stem cell transplantation, respiratory failure and high-grade fever appeared with severe thrombocytopenia and massive serum LDH elevation at day 50 after transplantation. Salvage combination chemotherapies had extremely limited effects against the disease, and we started to administer 375 mg/m of rituximab after its use for CD20-positive DLBCL was permitted according to the regulations established by the Japanese National Health Insurance system. The patient did not develop any major M. Kanno (&) Tumor Center, Nara Medical University Hospital, 840 Shijo-cho, Kashihara 634-8522, Japan e-mail: mkanno@naramed-u.ac.jp