Involvement of the central nervous system with acute myeloid leukemia
- Charles A Schiffer, MD
Charles A Schiffer, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
Involvement of the central nervous system (CNS) at the time of acute myeloid leukemia (AML) diagnosis is uncommon, and routine evaluation is not recommended for asymptomatic patients. Clinically overt CNS involvement developing at some point later during the course of treatment is also uncommon, perhaps related to the administration of high dose cytarabine as post-remission therapy.
This topic will discuss the epidemiology, clinical presentation, diagnosis, and treatment of CNS involvement in patients with AML. The clinical features, diagnosis, classification, treatment, and overall prognosis of AML are discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia" and "Induction therapy for acute myeloid leukemia in younger adults" and "Treatment of acute myeloid leukemia in older adults" and "Acute myeloid leukemia in children and adolescents".)
Incidence — The exact incidence of CNS involvement in patients with AML is unknown, but it is considerably less common than CNS involvement by acute lymphoblastic leukemia (ALL) in both adults and children [1,2]. As an example, CNS involvement was documented in 0.6 percent of adult patients at the time of initial presentation and in 2.9 percent upon relapse, in a review of 3261 adult patients enrolled in German clinical trials . However, in infants, potential CNS involvement was identified in 29 percent (395 of 1344 children) of those in two Children's Oncology Group trials .
The incidence of CNS leukemia appears to have decreased since the incorporation of high dose cytarabine (HiDAC; which can penetrate into the CNS) into initial induction and/or post-remission therapy. Prior to the use of HiDAC, meningeal disease developed in up to 20 percent of children and 16 percent of adults with AML .
Risk factors — CNS involvement is more common in patients with AML with the following features [1,2,4,5]:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Alakel N, Stölzel F, Mohr B, et al. Symptomatic central nervous system involvement in adult patients with acute myeloid leukemia. Cancer Manag Res 2017; 9:97.
- Johnston DL, Alonzo TA, Gerbing RB, et al. Central nervous system disease in pediatric acute myeloid leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer 2017; 64.
- Peterson BA, Brunning RD, Bloomfield CD, et al. Central nervous system involvement in acute nonlymphocytic leukemia. A prospective study of adults in remission. Am J Med 1987; 83:464.
- Holmes R, Keating MJ, Cork A, et al. A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22). Blood 1985; 65:1071.
- Shihadeh F, Reed V, Faderl S, et al. Cytogenetic profile of patients with acute myeloid leukemia and central nervous system disease. Cancer 2012; 118:112.
- Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol 2008; 9:257.
- Ranta S, Palomäki M, Levinsen M, et al. Presenting features and imaging in childhood acute myeloid leukemia with central nervous system involvement. Pediatr Blood Cancer 2017; 64.
- Howard SC, Gajjar A, Ribeiro RC, et al. Safety of lumbar puncture for children with acute lymphoblastic leukemia and thrombocytopenia. JAMA 2000; 284:2222.
- Howard SC, Gajjar AJ, Cheng C, et al. Risk factors for traumatic and bloody lumbar puncture in children with acute lymphoblastic leukemia. JAMA 2002; 288:2001.
- Vavricka SR, Walter RB, Irani S, et al. Safety of lumbar puncture for adults with acute leukemia and restrictive prophylactic platelet transfusion. Ann Hematol 2003; 82:570.
- van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol 2010; 148:15.
- Arber DA, Borowitz MJ, Cessna M, et al. Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med 2017; 141:1342.
- Sanders KE, Ha CS, Cortes-Franco JE, et al. The role of craniospinal irradiation in adults with a central nervous system recurrence of leukemia. Cancer 2004; 100:2176.
- Castagnola C, Nozza A, Corso A, Bernasconi C. The value of combination therapy in adult acute myeloid leukemia with central nervous system involvement. Haematologica 1997; 82:577.
- Thompson CB, Sanders JE, Flournoy N, et al. The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia. Blood 1986; 67:195.
- Mayadev JS, Douglas JG, Storer BE, et al. Impact of cranial irradiation added to intrathecal conditioning in hematopoietic cell transplantation in adult acute myeloid leukemia with central nervous system involvement. Int J Radiat Oncol Biol Phys 2011; 80:193.
- Walker GV, Shihadeh F, Kantarjian H, et al. Comprehensive craniospinal radiation for controlling central nervous system leukemia. Int J Radiat Oncol Biol Phys 2014; 90:1119.
- Frick J, Ritch PS, Hansen RM, Anderson T. Successful treatment of meningeal leukemia using systemic high-dose cytosine arabinoside. J Clin Oncol 1984; 2:365.
- Risk factors
- CLINICAL PRESENTATION
- Lumbar puncture
- - Overview
- - Technique
- - Findings
- Intrathecal chemotherapy
- - Administration
- - Methotrexate
- - Cytarabine
- - Thio-TEPA
- Cranial radiation
- Systemic chemotherapy
- Patients with ocular involvement
- RESPONSE EVALUATION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS