Contribution of single-photon emission computed tomography in the diagnosis and follow-un of CNS toxicity of a cytarabine-containing regimen in pediatric leukemia

Purpose: Cytarabine(ara-C) is one of the most effective chemotherapeutic ag ents in patients with acute leukemia (AL), with a clear dose effect. Use of high-dose ara-C is hampered, however, by a noticeable toxicity, particular ly to the CNS, We investigated the usefulness of CNS perfusion imaging with technetium-99m (Tc-99m)-hexamethyl-propylene-amine axime (HMPAO) single-ph oton emission computed tomography (SPECT) concurrent to magnetic resonance imaging (MRI) to specifically assess the effects of standard- and high-dose ara-C in children with AL Patients and Methods: Twenty-six perfusion studies using Tc-99m-HMPAO SPECT were performed in 12 children (age range, 4 to 15 years) with AL after ind uction therapy which consisted of a standard-dose ara-C, immediately after consolidation with high-dose ara-C, and later during follow-up (range, 6 to 44 months). the chemotherapy-related adverse events were monitored and cor related ta SPECT and MRI, Results: After the induction phase, all children were neurologically normal on MRI. On SPECT imaging, four children displayed a slightly heterogeneous perfusion. After high-dose am-C (4 to 36 g/m(2)), five children had regres sive neurologic signs of potential toxic origin. Of these five children, on ly one had an abnormal MRI scan, whereas all patients showed evidence of di ffuse cerebral and/or cerebellar heterogeneous perfusion on SPECT. the seve n other patients without any neurologic symptoms had normal MRI scans; SPEC T was normal for three patients and abnormal for four patients. On followup , for four children who had presented with clinical neurologic toxicity, SP ECT improved in three patients and remained unchanged in one patients. In t wo of these four children, delayed abnormalities (T2 white matter hypersign al and cerebellar atrophy) appeared on MRI scans, Conclusion: In our series,diffuse heterogeneous brain hypoperfusion is ofte n the sole early objective imaging feature identified by SPECT of high-dose ara-C neurotoxicity, where MRI still demonstrates normal pictures.