MD Anderson Cancer Center, Houston, TX
Simon Abi Aad , Naval Guastad Daver , Paolo Strati , Jorge E. Cortes , Guillermo Garcia-Manero , Michael Mathisen , Farhad Ravandi , Tapan M. Kadia , Susan Mary O'Brien , Carol Bivins , Sherry Pierce , Hagop M. Kantarjian , Elias Jabbour
Background: Despite CR rates of 70% with modern chemotherapeutic regimens, most pts with AML relapse. CNS relapses have become uncommon with the use of high-dose cytarabine based regimens. The features associated with a higher risk of CNS relapse are not defined. Methods: We analyzed adults who presented with AML and CNS relapses from 2000 until 2014. CNS leukemia was diagnosed by the presence of blasts in a cytocentrifuge preparation of CSF. Pts with blasts in the CSF together with high numbers of red blood cells (> 5) were not considered to have CNS disease if the blasts were high in the PB. Results: Of the 1312 pts with AML treated at our institution, 71 (5%) had CNS disease. Median age was 57 years. CNS involvement was detected after a median of 8 months from the initial diagnosis. 4 pts (6%) had isolated CNS relapse that was followed by systemic relapse after a median of 2 weeks. CNS involvement was detected in the setting of refractory AML in 31 pts (44%). 64 pts (90%) received previous high-dose cytarabine. 54 pts (76%) had neurologic symptoms at time of CNS relapse. CNS imaging was performed in 67 pts (94%): 41 (61%) had abnormal findings by MRI suggestive of CNS disease. 4 pts had zero cells with blasts detected on cytocentrifuge preparation only. None of the 4 pts had circulating blasts and all had abnormal findings on brain MRI suggestive of CNS relapse. 18 pts (25%) were FLT3-ITD mutated. CNS involvement was more commonly observed in young pts with increased WBC, BM blasts, and LDH, with M4/M5 phenotype, and FLT3/ITD mutated (12% versus 5%, p=0.003). Treatment for CNS disease consisted of IT chemotherapy in all pts, whole brain radiation therapy in 14, and spinal radiation in 8. Therapy was successful in clearing all signs of CNS disease in 29 (41%). 19 of the 29 pts (65%) subsequently had additional CNS relapses after a median of 3 months. The 2-year survival rate after CNS relapse was 13%. There was no difference in overall survival among patients with or without CNS disease. Conclusions: CNS relapse is a rare occurrence in AML (5%) and is associated with a poor prognosis. A high prevalence of FLT3-ITD mutations was observed in these pts. FLT3 mutational status and LDH level may identify patients with AML who may benefit from CNS prophylaxis.
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