Vincristine-induced fever in a child with rhabdomyosarcoma: cellular hypersensitivity to vincristine demonstrated by leukocyte migration test.

Abstract

To the Editor[colon] Febrile episodes are frequently encountered during the chemotherapy course, especially with neutropenia, but it is not always easy to evaluate the cause of fever. Fever induced by vincristine (VCR) is well known, but its pathophysiology is poorly understood. We describe here a case of VCR-induced fever, in which cellular hypersensitivity to VCR was demonstrated by leukocyte migration test (LMT). Fever repeatedly occurred after combination chemotherapy including VCR in a 2-year-old boy with advanced rhabdomyosarcoma, and it also occurred after a single administration of VCR. There were no other clinical symptoms except for fever, and laboratory tests showed normal findings. Fever resolved spontaneously within 24 hours without any antibiotics. The course with chemotherapy that consisted of cisplatin and actinomycin D was uneventful. The course with prophylactic administration of hydrocortisone just before VCR administration was also uneventful. These clinical observations suggested that an allergic response to VCR might be involved in the pathophysiology of fever. Leukocyte migration testing was performed according to the manner previously reported with a slight modification (1). The results of LMT are provided in Table 1. Migration index with VCR concentration of 2.5ng/mL and the patient's serum were significantly higher than that of normal controls (P [lt] 0.01). The LMT was considered positive at this concentration, and high migration index was interpreted as indicating the detection of leukocyte migration activating factor. Lymphocyte stimulation test with VCR was negative, with a stimulation index of 102[percnt].TABLE 1: Results of leukocyte migration testThe LMT is one of the sensitive tests for the detection of delayed type hypersensitivity (1). Concerning this method, Uno et al. (2,3) speculated that lymphocytes cultured with a stimulator secreted some cytokines in the culture medium, and the cytokines could inhibit or enhance the migration of human leukocytes (granulocytes). It may be considered that a hypersensitive reaction was reduced in the bioassay, such as LMT or lymphocyte stimulation test with cytotoxic drugs. However, in this case, leukocyte migration was enhanced despite the presence of VCR in the supernatant fluid. These findings indicated the possible involvement of cell-mediated hypersensitivity to VCR in the pathophysiology of fever in this patient. Only LMT with the patient's serum revealed a positive result. Because VCR is of relatively low molecular weight (923.05), it may be combined with some substances in the serum and form a complete antigen capable of stimulating lymphocytes. Ishii (4) reported that VCR-induced fever was observed in 9 of 31 children undergoing maintenance chemotherapy for leukemia or lymphoma. They also reported that the duration of fever was more prolonged during a chemotherapy course without corticosteroids than in those with corticosteroids, suggesting the possible involvement of an allergic mechanism. To our best knowledge, this is the first case of cellular hypersensitivity to VCR in VCR-induced fever. Fujimori (5) reported a case of hypersensitivity pneumonitis, in which delayed type hypersensitivity to paclitaxel was demonstrated by LMT. Leukocyte migration testing may be useful for the detection of cellular hypersensitivity to other cytotoxic drugs. In evaluating the cause of fever in patients with chemotherapy including VCR, physicians should pay attention to the possible involvement of an allergic mechanism. Chihaya Imai M.D. Katsuji Uno Ph.D. Toshio Kakihara M.D., Ph.D. Atsushi Tanaka M.D., Ph.D. Makoto Uchiyama M.D., Ph.D.