One year after her initial diagnosis
One year after her initial diagnosis, the patient presented back for the abrupt onset of symmetrical bilateral lower-limb weakness and numbness. The patient did not report other symptoms or history of trauma. Clinical examination revealed a healthy person except for a symmetrical proximal and distal bilateral lower limbs weakness and sensory loss with absence of deep tendon reflexes. Complete blood count, LDH, and electrolytes were within normal range. Contrast enhanced magnetic resonance imagery (MRI) of her lumbar spine showed mild anterolisthesis of L4 on L5. Brain MRI was normal for her age. Nerve conduction studies demonstrated acute inflammatory demyelinating neuropathy suggestive of Guillain–Barré syndrome. Subsequently, we performed a lumbar puncture that revealed pleiocytosis with 405 blast regulator of g protein signaling according to cytology and flow cytometry. Analysis of her BM aspirate showed 3% of blasts with positive CBFβ-MYH11 fusion transcript D, and reciprocal translocation between chromosomes 3 and 16 detected in 4% of examined cells,46,XX,t(3;16)(p14;q24)/46,XX. We retained the diagnosis of isolated AML CNS meningeal recurrence. Consequently, the patient received a chemotherapy protocol of standard FLAG-IDA dosage with intrathecal chemotherapy of methotrexate (10mg) plus dexamethasone (5mg) alternating with cytarabine (50mg) twice weekly. The patient noted complete resolution of her symptoms and her clinical exam was back to normal three weeks after initiating chemotherapy. She remains alive after six months without any complains.
Discussion Myelomonocytic and monocytic leukemias are the most common leukemia subtypes to affect extramedullary organs with CNS involvement occurring in 20% . Leukemia cells affect the CNS by various mechanisms that may advocate specific treatment approaches. Blasts may infiltrate leptomeninges causing meningeal leukemia, cranial nerves inducing cranial nerve palsies, or may precipitate into a solid collection known as myeloid sarcoma . Most commonly, patients with CNS leukemia are asymptomatic. Nevertheless, a small number of patients describe increased intracranial pressure manifesting with headache, stiff neck, mental derangement, papilloedema, nausea and vomiting. Case reports describe rare presentations of cranial nerve palsies and cauda equine syndrome [5–7]. Literature describes multiple risk factors for the occurrence of CNS relapse in adult patients with AML: French–American–British classification (FAB) M4/M5 subtypes, cytogenetic abnormality inversion 16, male sex, high white blood cell count at diagnosis, elevated serum lyzozyme and lactate dehydrogenase concentrations [2,8,9]. Aside from her gender, our patient had the other four mentioned risk factors. One recent paper reported a high prevalence of FLT3 mutations in AML patients with CNS relapse. Of particular significance is a recent multivariate analysis that demonstrated that the use of old instead of new generation therapeutic induction regimens is the only factor affecting CNS relapse . In the absence of a consensus for the optimal therapy for adult AML CNS recurrence, treatment approaches are extrapolated from studies of paediatric AML and acute lymphoblastic leukemia (ALL). Generally, isolated CNS leukemia relapse is considered a systemic disease independently of the BM status and requires systemic chemotherapy as local control is not sufficient. The optimal regimen is guided by the clinical presentation and pathophysiology of the CNS AML relapse. One study subdivided patients into meningeal leukemia, cranial nerve palsy, and cerebral parenchymal myeloid sarcoma and tailored their treatments accordingly . The study resulted in 70.6% CNS remission without affecting long-term survival (overall survival 6.64 months). Aside from case reports, only three small series report this entity. The first paper by Holmes et al. in 1987 describing CNS relapse in acute myelomonocytic leukemia reports 35% CNS relapse at a median of 19 months after complete remission . Another study showed CNS leukemia recurrence on follow up in 2.2% of cases, remitters had a median survival of 10 months whilst nonremitters survived two months only . One last article by Cuadron et al. in 2011 examined 458 adult patients with a diagnosis of non-promyelocytic AML and reported CNS involvement at first relapse in six patients of whom only two cases had isolated CNS relapse. The overall 5-year cumulative incidence of CNS relapse is 1.3% with a median of seven months (range 1–16 months) .