The authors’ observations
Temporary decreases in ANC are expected during chemotherapy, and the timing of onset and recovery is often well characterized. Prior to Day 15, the observed progressive marrow suppression was solely due to chemotherapy. However, because Mr. A’s ANC remained 0 µL longer than anticipated, reevaluation of clozapine’s effects was warranted.
Timing, clinical course, and comprehensive hematologic monitoring can provide important clues as to whether clozapine may be responsible for prolonged neutropenia. Though a prolonged ANC of 0 µL raised concern for clozapine-induced agranulocytosis (CIAG), comprehensive monitoring of hematologic cell lines was reassuring because CIAG selectively targets granulocytic cells (neutrophils).2 In contrast, chemotherapy can affect other cell lineages, including lymphocytes, red blood cells, and platelets, which causes pancytopenia.3 For Mr. A, though the clinical presentation of pancytopenia was significant and concerning, it was inconsistent with CIAG.
Additionally, the patient’s baseline risk of CIAG should be considered. After 18 weeks of clozapine treatment, the risk of CIAG decreases to a level similar to that associated with other antipsychotics.4,5 Therefore, CIAG would be unlikely in a patient treated with clozapine for more than 1 year and who did not have a history of neutropenia, as was the case with Mr. A.
While bone marrow biopsy can help differentiate between the causes of agranulocytosis,6 it is highly invasive and may not be necessary if laboratory evidence is sufficient. However, if a treatment team is strongly considering discontinuing clozapine and there are no suitable alternatives, a biopsy may provide additional clarification.
TREATMENT CAR T-cell therapy and cancer remission
Clozapine is continued with daily monitoring. On Day 19, Mr. A’s ANC increases, reaching 2,600 µL by discharge on Day 40. Mr. A remains psychiatrically stable throughout his hospitalization and does not experience any complications associated with neutropenia, despite its prolonged duration.
Continue to: Unfortunately, multiple cycles of...