PB1763 CNS INVOLVEMENT AT PRESENTATION IN AML: A RETROSPECTIVE CASE SERIES
Authors: Jain A. , Dhingra N. , Seth T. , Mahapatra M. 
Published: June 2019

Background:

Central nervous system involvement at present in Acute Myeloid Leukemia is uncommon. When it occurs, the course is less predictable and prognostication and therapy guidelines are less lucid than with acute lymphoblastic leukemia.

Aims:

To review the clinical profile, presentation, imaging findings, CSF positivity, management, and outcomes of AML patients with CNS involvement at the time of initial presentation.

Methods:

We retrospectively collected the clinicopathological profile, management and outcome data of AML patients with CNS involvement over the past 5 years at our Institute. Patients with CNS involvement by CSF positivity or direct CNS or spinal cord involvement were included. It is our policy to perform CNS evaluation at presentation in all Pediatric AML or with symptoms suggestive of CNS involvement e.g. paraparesis, seizures, proptosis.

Patients with paraspinal masses causing cord compressions, intra cranial bleed, intraretinal bleed, CNS involvement at relapse, or possible CNS involvement but without either CSF or imaging confirmation were excluded.

Results:

Eight patients fulfilled our inclusion criteria. Of these 4 were adults and 4 were pediatric patients (<18 years age). Only 1 (12.5%) amongst these was a female. Cytogenetics were t(8:21), t(8:21) +8, t(8:21) +8 +19, AML with t(9:22) in 1 patient each with rest 50% patients having normal cytogenetics.

CSF analysis was positive for malignant cells in 3 patients, not done in 1 (because patient was very sick) and negative in the rest. Imaging was not done in 2 patients who were CSF positive with no focal neurological deficits, and was normal in 1 patient with 3rd cranial nerve palsy. Leptomeningeal involvement was present in 2 patients, cavernous sinus and falx cerebri involvement in 1, paravertebral deposits and cord enhancement in 1, and paravertebral and infratemporal deposits in another.

All patients were treated with 3+7 induction followed by HIDAC with IT therapy with each cycle and 2 patients received RT as well. Ph positive AML was taken up for transplant after 2nd induction with HIDAC and is currently undergoing the same. 1 patient was not given chemotherapy because she had severe fungal pneumonia and expired.

Six out of the 7 treated patients showed near complete resolution of CNS symptoms/imaging findings after chemotherapy. 1 patient with paraplegia had persisting spinal cord lesions despite 2 induction chemotherapies, IT and RT. Four patients relapsed – one CNS relapse, two CNS and BM relapse and 1 patient had BM relapse in the background of persisting CNS disease. Currently only 3 patients are alive, one of whom is undergoing Allogenic HSCT.

Summary/Conclusion:

CNS involvement in AML is rare at presentation. Presentation can vary from asymptomatic CSF positivity, to isolated cranial nerve involvement to paraplegia and recurrent seizures. Screening and Management protocols are not clearly defined. NCCN recommends screening before first consolidation in patients with monocytic differentiation, Mixed phenotypic acute leukemia, WBC >40000at diagnosis, extra medullary disease or high risk APML. For major neurological signs imaging should be performed. If no signs or symptoms then CSF should be done. Treatment with standard AML chemotherapy with IT/RT seems to have short term effects only. Overall prognosis in this group of patients seems poor with a high rate of relapse and mortality. Larger studies are required to address relevant questions such as high risk patients who should be screened, indications of performing CSF analysis and imaging, and adequate management.

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