Abstract

Myelodysplastic syndromes are a group of oligoclonal hematologic disorders characterized by variable cytopenias and dysplastic changes in the bone marrow. Novel, remittive therapies designed to treat the cytopenias of myelodysplasia, induce apoptosis, differentiation, and antiangiogenesis, in vitro. The success of remittive therapy for myelodysplasia typically depends on clinical criteria of hematopoietic recovery but seldom address functional disturbances. We present a case of an 81 year old man with a one-year history of mild pancytopenia (ANC 0.7 x 103/μL, Hemoglobin 10.3 g/dl MCV 101.7, platelets 51 x 103/μL). A bone marrow biopsy at diagnosis revealed findings consistent with refractory anemia with excess blasts; an initial karyotype revealed no clonal cytogenetic abnormalities. Four months after diagnosis, the patient developed transfusion-dependent thrombocytopenia. A repeat bone marrow biopsy showed equivalent pathology, but cytogenetic analysis demonstrated trisomy 8 in 4 of 20 cells karyotyped. The patient was started on a 12-week trial of paricalcitol, a vitamin D derivative. His treatment course was characterized by persistent moderate pancytopenia and hypercalcemia. Nine months after diagnosis, the patient was admitted to hospital with one week of headache, fever, and visual disturbance. Leukocytes were 28.67 x 103/μL with 11% segmented neutrophils and 70% band forms, Hgb 8.9 g/dl, and platelets 73 x 103/μL. Over the first 24 hours, the patient developed rapidly progressive proptosis leading to MRI of the skull that revealed an abnormal signal in the left frontal lobe. A CT 2 days later revealed extensive sinusitis with a left orbital mass. At resection, rhinocerebral mucormycosis involving the paranasal sinuses, orbit, and cerebral cortex was identified. We performed neutrophil function studies which showed two distinct populations; 59% showed normal oxidative burst capacity, but 41% showed impaired capacity. NBT test also sugested a broadened population of stimulated neutrophils. By light microscopy, numerous pale, agranular, Pelgeroid cells were visible. Despite extensive resection and systemic antibiotics, the patient expired on the 25th hospital day. This case illustrates that normal neutrophil number, in the setting of myelodysplasia, may not denote normal neutrophil function. Functional criteria of response should be considered in clinical studies of remittive therapy for myelodysplasia.

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