TY - JOUR
T1 - Toxic Leukoencephalopathy following Fludarabine-Associated Hematopoietic Cell Transplantation
AU - Beitinjaneh, Amer
AU - McKinney, Alexander M
AU - Cao, Qing
AU - Weisdorf, Daniel J
PY - 2011/3
Y1 - 2011/3
N2 - Toxic leukoencephalopathy has been more thoroughly investigated during the last decade because of the advance of magnetic resonance imaging (MRI) techniques. We analyzed fludarabine (Flu)-associated hematopoietic cell transplantation (HCT), resulting in severe leukoencephalopathy (n = 39/1596, 2.4%), and describe 3 clinical syndromes with unique clinical and radiographic characteristics. Posterior reversible encephalopathy syndrome (PRES) presents predominantly with seizures, persistent headache, and vision changes, along with variable mental status alterations. PRES is likely to be reversible, particularly after withholding cyclosporine (CsA). Acute toxic leukoencephalopathy (ATL) presents with cognitive dysfunction, decreased levels of consciousness, and vision changes. Other leukoencephalopathy (OLE) includes patients who behave similar to the ATL group, but with less prominent deep white matter changes on MRI. ATL and OLE are less likely to be reversible. The neurologic syndromes correlate with different MRI patterns. In PRES, subcortical and cortical involvement on MRI is associated with seizure, blurred vision, and dysarthria versus ATL and OLE, which involve deep white matter and cause mainly cognitive dysfunction. The different syndromes also carry different prognoses. All patients with Flu-associated encephalopathy had a median overall survival of only 169 days. Those with ATL had shorter overall survival (median 66 days) than patients with PRES (median 208 days). Potential risk factors for Flu-associated encephalopathy were older age, poor renal function, Flu dose, previously treated central nervous system (CNS) disease, or previous Flu-based transplant conditioning. Additional risk factors for PRES CNS toxicity are CsA use and acute hypertension. Flu pharmacokinetic studies may be useful to reduce life-threatening Flu-associated risks of neurotoxicity.
AB - Toxic leukoencephalopathy has been more thoroughly investigated during the last decade because of the advance of magnetic resonance imaging (MRI) techniques. We analyzed fludarabine (Flu)-associated hematopoietic cell transplantation (HCT), resulting in severe leukoencephalopathy (n = 39/1596, 2.4%), and describe 3 clinical syndromes with unique clinical and radiographic characteristics. Posterior reversible encephalopathy syndrome (PRES) presents predominantly with seizures, persistent headache, and vision changes, along with variable mental status alterations. PRES is likely to be reversible, particularly after withholding cyclosporine (CsA). Acute toxic leukoencephalopathy (ATL) presents with cognitive dysfunction, decreased levels of consciousness, and vision changes. Other leukoencephalopathy (OLE) includes patients who behave similar to the ATL group, but with less prominent deep white matter changes on MRI. ATL and OLE are less likely to be reversible. The neurologic syndromes correlate with different MRI patterns. In PRES, subcortical and cortical involvement on MRI is associated with seizure, blurred vision, and dysarthria versus ATL and OLE, which involve deep white matter and cause mainly cognitive dysfunction. The different syndromes also carry different prognoses. All patients with Flu-associated encephalopathy had a median overall survival of only 169 days. Those with ATL had shorter overall survival (median 66 days) than patients with PRES (median 208 days). Potential risk factors for Flu-associated encephalopathy were older age, poor renal function, Flu dose, previously treated central nervous system (CNS) disease, or previous Flu-based transplant conditioning. Additional risk factors for PRES CNS toxicity are CsA use and acute hypertension. Flu pharmacokinetic studies may be useful to reduce life-threatening Flu-associated risks of neurotoxicity.
KW - Fludarabine
KW - Hematopoietic cell transplantation
KW - Posterior reversible encephalopathy syndrome
KW - Toxic leukoencephalopathy
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U2 - 10.1016/j.bbmt.2010.04.003
DO - 10.1016/j.bbmt.2010.04.003
M3 - Review article
C2 - 20399878
AN - SCOPUS:79551681652
SN - 1083-8791
VL - 17
SP - 300
EP - 308
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -