Isolated cerebrospinal fluid relapse of acute myeloid leukemia status post stem cell transplant: A neuroleukemiosis manifesting as polyneuropathy
Authors: Yue Zhao, Benjamin Mullenbach, Endi Wang
Journal: American Journal of Hematology (2020)

The patient was a 19 year-old male who was diagnosed with acute myeloid leukemia (AML) with Homozygous CEBPA mutation (C-terminal in-frame duplication) in addition to a pathogenic NRAS mutation and three associated GATA2 mutations. He received chemotherapy followed by matched related hematopoietic stem cell transplant (HSCT). The post-transplant course was complicated with acute graft vs host disease, which was treated with tacrolimus and prednisone (10 mg daily). Although demonstrating initial engraftment, bone marrow biopsy 76 days after the transplant showed early relapse. He was then treated with azacitidine/venetoclax followed by a donor lymphocyte infusion, and eventually underwent remission with a complete engraftment of donor cells 193 days after the transplant. Approximately 14 months after the transplant, the patient complained of back pain and general weakness. The patient developed progressive numbness and tingling in his bilateral upper extremities and his left lower extremity. This was followed by an involvement of the right lower extremity and right side facial droop. He also reported a difficulty in urination and defecation with associated numbness of his testicles and buttocks. Magnetic resonance imaging (MRI) of brain and spine showed multiple enlarged and enhancing cervical (Figure 1A), thoracic (Figure 1B), lumbar, and sacral nerve roots including the cauda equina (Figure 1C), as well as abnormal enhancement of the right facial nerve. Neurologic evaluation suggested a diagnosis of polyneuropathy, including a possibility of Guillain-Barre syndrome. Lumbar puncture was performed and examination of cerebrospinal fluid (CSF) showed markedly increased mononucleated cells (1323/μL; reference: 0-5). Microscopic evaluation revealed many blasts with cytological features suggestive of myeloid blasts (Figure 1D). Flow cytometric analysis demonstrated 88% blasts that were positive for CD34 and myeloid antigens CD117, CD13 and CD33 with aberrant CD7, the immunophenotypic profile similar to that detected in the diagnostic analysis. The bone marrow examination exhibited trilineage hematopoiesis with complete engraftment of donor cells and no increase in blasts, suggesting an isolated CSF relapse with neuroleukemiosis. The patient started intrathecal methotrexate and hydrocortisone, and re-instituted azacitidine/venetoclax. Sixteen days after intrathecal (three doses) and systemic chemotherapy (two cycles), his neurologic symptoms improved with relieved pain, tingling and urinary retention. Lumbar puncture examination showed no morphologic or flow cytometric evidence of leukemic blasts in CSF fluid. Cranial radiation was considered at the time when this manuscript was prepared. Extramedullary relapse of AML occurs in approximately 3% of the cases after HSCT, and a significant fraction demonstrates isolated CSF relapse.1, 2 The underlying mechanism is unclear, but may be explained by a sanctuary site of CSF with insufficient patrol by anti-leukemic T-cells of the donor origin.1 Although extramedullary relapse of AML overall shows better survival than bone marrow relapse, the prognosis of isolated CSF relapse as a special extramedullary presentation is unknown largely due to rarity of the reported cases. As seen in extramedullary relapse in general, isolated CSF relapse of AML typically predicts subsequent systemic relapse, portending a dismal clinical outcome.1 Because a standard therapy with efficacy has not been established, the better approach for the management of CSF relapse after HSCT may focus on antecedent recognition of the risk factors and early diagnosis by increased surveillance. Interestingly, leukemic involvement in central nervous system often presents with parenchyma lesion or dural/meningeal enhancement.3 However, spinal nerve root involvement with clinical manifestations and radiological findings resembling polyneuropathy or lumbosacral plexopathy as seen in this case is extremely rare.4 Given the nonspecific radiological features and unusual clinical presentation, we advocate a diagnostic vigilance and emphasize examination of CSF in patients with history of AML status post HSCT and neurologic symptoms suggestive of spinal neuropathy, in order to avoid a delay in diagnosis. Acknowledgement of the authorsʼ contribution to the manuscript: Y.Z. prepared the images, and wrote the manuscript; B.M. interpreted the images and edited the manuscript; E.W. organized the study, and wrote the manuscript. The authors declare no potential conflicts of interest.