CASE REPORTS G-CSF Plasma Levels in Clozapine-Induced Neutropenia Marek Jauss, Johannes Pantel, Egon Werle, and Johannes Schro ¨der Background: Clinical reports emphasize the therapeutic usefulness of granulocyte colony-stimulating factor (G- CSF) in clozapine-induced granulocytopenia. Only sparse information exists, however, on the natural course of endogenous G-CSF plasma levels in this condition. Methods: We monitored G-CSF and white blood cell (WBC) counts in a 73-year-old patient who developed granulocytopenia while being treated with clozapine for schizoaffective disorder. Clozapine treatment was discon- tinued immediately, and G-CSF serum levels were deter- mined repeatedly during the clinical course. Results: Whereas WBC counts increased again within 6 days after discontinuation of clozapine, G-CSF level decreased significantly within the same period. The rapid decrease of endogenous G-CSF levels paralleled by a normalization of neutrophil count was interpreted as the result of an intact regulatory mechanism of granulocyto- poesis. Therefore G-CSF therapy was not initiated. Owing to lack of therapeutic alternatives, it was decided to reintroduce clozapine. G-CSF levels decreased further, accompanied by an increase of WBCs, indicating stable bone marrow functioning. Conclusions: Based on this observation, we assume that the course of G-CSF and WBC counts indicated an abortive form of toxic bone marrow damage with subse- quent recovery. We conclude that monitoring of G-CSF levels may serve as a useful tool in the follow-up of patients in whom clozapine-induced bone marrow damage is suspected. Biol Psychiatry 2000;48:1113–1115 © 2000 Society of Biological Psychiatry Key Words: Clozapine, neutropenia, granulocyte colony- stimulating factor, granulocytopenia Introduction C lozapine is an atypical neuroleptic agent with marked antipsychotic effects even in otherwise treatment- resistant psychoses. The clinical use of clozapine is limited by potential side effects, in particular because of the excessive risk of agranulocytosis (0.80% at 1, 0.91% at 2 years; Alvir et al 1993). After initiation of clozapine therapy a peak in the number of neutrophils is considered as an indicator associated with an elevated risk of subse- quent granulocytopenia (Alvir et al 1995). It has been suggested that this early peak may refer to a release of granulocytes from endothelial cells, indicating an autoim- mune process with subsequent bone marrow damage. There are only a few reports that emphasize the potential efficacy of granulocyte colony-stimulating factor (G-CSF) as a treatment in cases where clozapine therapy induced severe granulocytopenia (Gerson et al 1992; Gruner et al 1994). Application of G-CSF is limited, owing to its high costs and to potential side effects (i.e., allergic reactions or thrombocytopenia). Because the natural course of endog- enous G-CSF plasma levels induced by granulocytopenia during clozapine treatment was up to now not described, we report on the following case. Case Report A 73-year-old female Caucasian patient developed neutro- penia after 4 years of uneventful clozapine treatment (100 mg/day) for schizoaffective disorder. An idiopathic Par- kinson’s disease was diagnosed 3 years ago and treated with the antimuscarine drug metixen (15 mg/b.i.d.) and L-dopa (187.5 mg/day). White blood cell (WBC) count was measured at regular intervals and revealed leukocyte levels ranging from 5.4 to 9.9/nL. The patient’s human leukocyte antigen haplotype did not correspond to that which has been reported to be associated with higher incidence of clozapine-induced agranulocytosis (Lieber- man et al 1990). The patient was admitted because the WBC count had dropped to a granulocyte level of 2.5/nL (neutrophils: 34%) with no clinical signs of febrile infec- tion. On admission, clozapine treatment was discontinued immediately. Subsequent control of WBC count revealed a slight increase to 3.1/nL (neutrophils: 60%). Six days after admission, the WBC count was within the normal range with 4.3/nL (neutrophils: 79%), accompanied by a decrease of G-CSF level (Quantikine HS Kit, R&D Systems, Wiesbaden, Germany) from 35.4 pg/mL on day 3 to 17.2 pg/mL on day 8 (5–95 percentile range 9.1–51.2 pg/mL in 37 normal persons). Shortly after cessation of clozapine administration a reexacerbation of the schizoaf- From the Department of Psychiatry, Section of Geriatric Psychiatry (MJ, JS, JP) and Central Laboratory, Medical Clinic and Policlinic (EW), University of Heidelberg, Heidelberg, Germany. Address reprint requests to Marek Jauss, University of Giessen, Department of Neurology, Am Steg 14, Giessen D-35385, Germany. Received November 15, 1999; revised April 6, 2000; revised June 7, 2000; accepted June 7, 2000. © 2000 Society of Biological Psychiatry 0006-3223/00/$20.00 PII S0006-3223(00)00963-X