Clozapine therapy throughout myelosuppressive chemotherapy: regulations without standardization

Dear Editor,IntroductionClozapine is considered a preferred agent for severalpsychotic disorders and the drug of choice fortreatment-resistant schizophrenia [1]. Clozapine-inducedagranulocytosis is rare but necessitates close monitoringof blood cell counts during treatment [2]. A safeguardwas introduced when the United States Food and DrugAdministration (FDA) provided oversight of what isnow known as Novartis Pharmaceuticals Corporation(Novartis), the only manufacturer of clozapine at thetime, during implementation of a hematological monitor-ing system to minimize the risk of agranulocytosis andpotentially fatal consequences [3].Today, clozapine is a generic product availablethrough numerous manufacturers each maintaining anindependent registry database functionally identical tothe Clozapine National Registry (CNR) created and op-erated by Novartis. Providers adhere to registry proto-cols through provision of routine blood cell countresults. White blood cell count (WBC) or absolute neu-trophil count (ANC) values below the predeﬁned criticalthresholds precipitate placement of the correspondingpatient in a ‘do not rechallenge’ category. All registriesreport non-rechallenge patients to the CNR for place-ment on a National Non-rechallenge Masterﬁle. Thisclassiﬁcation is intended to prohibit patients from re-ceiving clozapine from any and all manufacturers; how-ever, conformity is not universal. Various manufacturersunconditionally adhere to the non-rechallenge status ofpatients, while others allow some patient continuationor intermittent temporary cessation and recommence-ment on an individualized basis.When patients with treatment-refractory schizophreniaand concurrent malignancy require myelosuppressive che-motherapy, the optimal approach for management is un-clear [4]. We present a patient with newly diagnosedhigh-grade lymphoma requiring chemotherapy that wasmaintained on clozapine for over 7 years and discuss theclinical and administrative challenges surrounding contin-uation of clozapine therapy.Patient caseA healthy 55-year-old male with a 30-year history ofschizoaffective disorder, stable for over 7 years onclozapine 250 mg and ziprasidone 60 mg daily since2001, was admitted to our institution for evaluation ofsevere abdominal pain. Computed tomography imagingrevealed diffuse bulky lymphadenopathy with massesin the skeletal muscle, orbit, adrenal glands and cardiacatrium. Excisional lymph node biopsy was diagnosticfor Burkitt Lymphoma. Bone marrow evaluation demon-strated a slightly hypercellular marrow, normal trilineagehematopoiesis and no evidence of lymphomatous inﬁl-trate. Cerebrospinal ﬂuid analysis was negative formalignancy.The patient described a signiﬁcant history of difﬁcultyachieving psychiatric symptom stabilization with medica-tion management. His schizoaffective disorder was re-ported refractory to risperidone, olanzapine andziprasidone. Additionally, the patient’s symptoms wereinadequately controlled with clozapine monotherapy.The combination of clozapine and ziprasidone success-fully controlled his psychotic and mood symptoms, andat the time of the lymphoma diagnosis, the patient was ad-amant about maintaining his current medication regimen.The high-grade nature of the lymphoma and impending