Rituximab(Drug information on rituximab) (Rituxan) was recently approved for use in relapsed and previously treated low-grade non-Hodgkins lymphoma (NHL); however, little data exist regarding the safety of this agent in patients with hematologic malignancies who have a high number of tumor cells in the blood. We describe our preliminary experience with two such patients in whom we noted a rapid reduction of blood tumor cells, which was associated with severe pulmonary infusion-related toxicity and thrombocytopenia. Two additional patients were collected from physician-submitted reports of adverse events related to rituximab treatment.
Pretreatment characterization of these patients included a median age of 60 years (range, 26-73 years) with the diagnosis of B-prolymphocytic leukemia (B-PLL; N = 2), chronic lymphocytic leukemia (CLL; N = 1), or transformed non-Hodgkins lymphoma (NHL; N = 1). All of these patients had elevated leukocyte counts as a consequence of blood tumor involvement, bulky adenopathy, and organomegaly.
All four patients developed a unique syndrome of severe infusion-related reactions characterized by fever (N = 4), rigors (N = 4), and bronchospasm with associated hypoxemia (N = 3), requiring temporary cessation of rituximab therapy. Concurrent with these symptoms was a rapid decrement in circulating tumor cell load (mean pretreatment tumor cell load, 98 × 109/L [range, 73-132 × 109/L] vs mean posttreatment tumor cell load, 11 × 109/L [range, 3.7-24.6 × 109/L]) with mild laboratory evidence of rapid tumor lysis. Thrombocytopenia, a finding not commonly associated with rituximab therapy, was noted in all four patients (mean pretreatment platelet count, 145 × 109/L; [range, 57-277 × 109/L] vs mean posttreatment platelet count, 56 × 109/L [range, 2-120 × 109/L]), requiring transfusion in one case.
Symptoms of this syndrome required hospitalization but resolved with supportive care. Subsequent rituximab treatments were well tolerated in all patients. Two subsequent patients with CLL and high blood tumor counts have been treated at our institution utilizing stepped-up dosing (100 mg on day 1 followed by completion of the remaining therapy on day 2) with demonstrated efficacy and thrombocytopenia but minimal infusion-related toxicity.
CONCLUSION: Rituximab administration in patients with hematologic malignancies who have blood tumor cell involvement may be associated with a higher frequency of severe initial infusion-related reactions and thrombocytopenia, mandating careful clinical monitoring. Given the preliminary activity of rituximab in these patients, future studies in CLL and PLL possibly utilizing a stepped-up dosing schedule appear warranted.