Leukemia: neurologic complications

Jon Glass MD (Dr. Glass of Thomas Jefferson University has no relevant financial relationships to disclose.)
Amy A Pruitt MD, editor. (

Dr. Pruitt of the University of Pennsylvania School of Medicine has no relevant financial relationships to disclose.

Originally released August 28, 2007; last updated March 20, 2018; expires March 20, 2021

This article includes discussion of leukemia: neurologic complications, meningeal metastasis, parenchymal metastasis, chloroma (granulocytic sarcoma), cerebrovascular complications of leukemia, posterior reversible encephalopathy syndrome (PRES), infectious complications of leukemia, complications of radiation therapy and chemotherapy, complications of graft-versus-host disease, metabolic complications of leukemia, and paraneoplastic disorders associated with leukemia (paraneoplastic necrotizing myelopathy). The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Leukemia is defined as a group of neoplasms characterized by circulating malignant cells arising from granulocytic or lymphoid precursors. Acute leukemias are distinguished by the presence of immature cells, whereas chronic leukemias are characterized by the presence of mature-appearing cells and are more indolent than acute leukemias. The primarily hematogenous nature of leukemia and its aggressive treatment poses a risk for significant neurologic morbidity. With increased recognition of the potential for the development of neurologic disorders associated with leukemia, strategies (such as central nervous system prophylaxis for acute lymphocytic leukemia) have been utilized to prevent neurologic morbidity. However, neurologic syndromes may be unavoidable. Leukemia can cause neurologic morbidity in a variety of ways. Direct effects of leukemia on the nervous system include the formation of mass lesions (chloroma), direct parenchymal infiltration, conversion of chronic lymphocytic leukemia to a non-Hodgkin lymphoma (Richter syndrome), or, most commonly, meningeal metastasis. Cerebrovascular and hematologic manifestations include thrombosis, hemorrhage, and hyperviscosity syndromes resulting in vascular occlusion by leukemic cells. Hemorrhage may also be in direct toxicity due to treatment-related thrombocytopenia. Toxic and iatrogenic complications include effects of chemotherapy and radiation therapy, the unique effects of bone marrow or stem cell transplantation, infection, and about disturbances.

Key points


• Leukemia is a heterogeneous group of diseases, and direct neurologic complications may differ based on the type of leukemia. However, the indirect complications or complications of treatment are very similar.


• Direct effects of leukemia on the nervous system include parenchymal, skull base, and meningeal metastases.


• Indirect effects of leukemia on the nervous system include cerebrovascular complications, such as stroke or hemorrhage from hyperviscosity syndromes, and infection or other iatrogenic complications.


• Long-term neurologic toxicity has been reduced with the use of less neurotoxic prophylactic measures, such as intrathecal chemotherapy rather than whole brain radiation therapy.

Historical note and terminology

Leukemia is a heterogeneous group of diseases with origins in the blood-forming cells of bone marrow. Bone marrow stem cells divide into primarily 2 lineages. The myeloid stem cell line has the potential to divide into red blood cells, platelets, granulocytes, and monocytes. The lymphoid cell line has the potential to divide into lymphocytes. Leukemias are classified based on their origin in the myeloid stem cell line (myelogenous leukemias) or the lymphoid stem cell line (the lymphocytic leukemias).

Leukemias of either type are further classified as either chronic or acute. In acute leukemias, abnormal cells grow rapidly and remain immature. These rapidly growing cells infiltrate bone marrow and blood as well as normal tissues with a fulminant course if left untreated. Acute leukemias affect both children and adults. Acute lymphocytic leukemia accounts for approximately 65% of acute leukemias in children and is more common in children than adults (Pui and Evans 2006). Acute myelocytic leukemia can also affect children and adults and is the most common type of acute leukemia in adults. The disease tends to be more indolent in the chronic leukemias than in the acute leukemias. Cells tend to mature, though abnormally, with immune system impairment and accumulation of tumor cells in organs. The chronic leukemias almost exclusively affect adults. Chronic lymphocytic leukemia is approximately twice as common as chronic myelocytic leukemia and is more indolent than chronic myelocytic leukemia, with prolonged survival. Chronic myelocytic leukemia has a worse prognosis than chronic lymphocytic leukemia, though a targeted therapy (imatinib) has resulted in prolonged, progression-free, and overall survivals (Hehlmann et al 2007). Chronic lymphocytic leukemia may also convert to an acute lymphocytic leukemia or lymphoma (Chiorazzi et al 2005).

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