Brain perfusion in adult patients with acute myeloblastic leukemia before and after cytosine arabinoside.

PURPOSE: High-dose (HD) cytosine arabinoside (ara-C) is a major treatment in acute myeloblastic leukemia (AML) that can lead to cerebellar complications, although electroencephalogram, computed tomography, and magnetic resonance imaging remain normal. We conducted a prospective study to evaluate brain perfusion with single-photon emission computed tomography (SPECT) in adult patients before and after receiving ara-C.

PROCEDURES: Forty-three patients were pre-included, and 20 reached a complete remission. These 20 patients were definitively included and underwent three technetium-99m hexamethyl-propylene-amine oxime (HMPAO) SPECT acquisitions with a double-head camera: SPECT1 at AML diagnosis, SPECT2 after induction (conventional ara-C dose), and SPECT3 during HD ara-C treatment. All the included patients underwent six series of neurological and cognitive examinations: N1, N2, and N3 at the time of SPECT1, SPECT2, and SPECT3, respectively; N4 during HD ara-C treatment; N5 (at 10 days); and N6 during follow-up (at 6 months). Statistical parametric mapping (SPM2) was used to test perfusion changes. A specific method based on random walk (RW) was used to analyze diffuse brain perfusion heterogeneity.

RESULTS

No neurological adverse effect was observed, and all neurological and cognitive examinations remained normal. Between SPECT1 and SPECT2, SPM2 analysis showed a decrease in cerebral blood flow, i.e., in the cerebellum, in the occipitoparietal cortex, and in the thalamus. No significant difference was observed between SPECT2 and SPECT3 or between SPECT1 and SPECT3. RW analysis showed no significant difference in perfusion heterogeneity between the three SPECTs.

CONCLUSIONS

HMPAO SPECT demonstrated a decrease in thalamus, cerebellar, and parieto-occipital perfusion after conventional doses of ara-C in AML patients, although the neurological examinations were normal and the patients had no neurological adverse effects.