Letter to the Editor Cardiac Toxicity During Rituximab Administration V. GARYPIDOU, V. PERIFANIS, K. TZIOMALOS* and S. THEODORIDOU Haematology Dept. of 2nd Prop Dept. of Internal Medicine, Aristotelian University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece To the Editor, During the last few years, therapy for hematological malignancies is rapidly moving from nonspecific, aggres- sive, cytotoxic regimens toward treatments with specific molecular targets. Rituximab was the first monoclonal antibody approved for the treatment of non-Hodgkin lymphoma (NHL) and is being extensively used since. It binds specifically to the antigen CD20 which is located on pre-B and mature B lymphocytes and on 4 90% of B-cell non-Hodgkin’s lymphomas (NHL) but not on hemato- poietic stem cells or other normal tissues, regulates an early step in the activation process for cell cycle initiation and differentiation and is thus an ideal target antigen for antibody therapy of B-cell malignancies. Possible mechanisms of cell lysis include complement-dependent and antibody-dependent cell mediated cytotoxicity along with direct induction of apoptosis [1]. Rituximab shows significant activity in non-Hodgkin lymphomas and B-cell chronic lymphocytic leukemia (B-CLL) [2 – 4]. The more frequent adverse effects include infusion-related reactions such as fever, rigors, dyspnea and fatigue. The case of a patient, who developed an acute coronary syndrome during the first administration of rituximab, is described here. A 71-year-old male patient was diagnosed with B-CLL 5 years earlier. He was treated with chlorambucil during the previous year because of disease progression but without response. There were an 8-year history of type 2 diabetes mellitus and a 10-year history of hypertension. The patient had also suffered a myocardial infarction 12 years previously, and a percutaneous transluminal coronary angioplasty was performed 11 years previously. On physical examination cervical, axillary and inguinal lymph nodes were bilaterally enlarged and moderate splenomegaly was also noticed. The laboratory values included WBC 142,000 ml (97.4% lymphocytes), Hb 10.8 g/dl, PLT 67,000 ml, LDH 306 IU/l and direct Coombs ( + ) IgG. The immunologic phenotype included CD5 (95%) CD(19 95%) CD20 (95%) CD 22 (95%) CD23 (95%) CD25 (95%) CD25 75%, k-chain 90%, CD11c 50%, CD5 + CD19 + 95%, HLA-DR 95%, FMC7 15%. The electrocardiogram (ECG) showed a Q-wave in lead III and prominent T wave inversion in leads III and aVF. We decided to treat the patient with rituximab (375 mg/m 2 i.v. per week for at least four consecutive weeks). Premedication, consisting of acet- aminophen, diphenydramine and methylprednisolone, was given before the initiation of the infusion. Rituximab was administered at a steady rate of 50 mg/h. Four hours after the initiation of the first infusion the patient developed substernal pain radiating in neck and left arm, along with palpitations. The ECG showed sinus tachycardia with no ST-segment or T-wave changes and the biochemical cardiac markers were not elevated. The pain resolved with the administration of nitroglycerin sublingually and the infusion was interrupted. After 2 h the infusion was resumed at the same rate and 30 min later the patient developed an identical pain that subsided when the infusion was stopped. The administration of rituximab was discontinued. During the next few days, there was no elevation of the biochemical cardiac markers or ECG changes. Frequency and severity of first-dose adverse events of rituximab correlate with the number of circulating B cells at baseline due to the excessive release of cytokines (namely TNF-a, IL-6 and IL-8) and activation of the complement system [5 – 6]. It is possible that in our patient these bioactive molecules caused coronary vasoconstriction, platelet activation or rupture of an atherosclerotic plaque and thus led to the development of the unstable coronary syndrome. In conclusion, careful monitoring during the administration of monoclonal antibodies is mandatory, especially in patients with preexisting cardiac disease. *Corresponding author. 63, Solonos str, Thessaloniki 542 48, Greece. Tel.: 00302310823487. E-mail: ktziomalos@yahoo.com Leukemia & Lymphoma, January 2004 Vol. 45 (1), pp. 203–204 ISSN 1042-8194 print/ISSN 1029-2403 online # 2004 Taylor & Francis Ltd DOI: 10.1080/10428190310001607160