Management of CNS Disease in Pediatric Acute Lymphoblastic Leukemia

Incidence and prognostic value of central nervous system involvement in infants with B‐cell precursor acute lymphoblastic leukemia treated according to the MLL‐Baby protocol

“…The CNS represents a sanctuary in which leukemia cells are protected from and may thus escape systemic chemotherapy to thus serve a potential source of relapse. 22 BCP-ALL in infancy, especially cases with KMT2A-r, is typically characterized by a high frequency of initial CNS leukemia. 3 In the present study of a relatively large cohort of infants with BCP-ALL, the incidence of CNS leukemia (CNS-3 status) was comparable to that obtained by other groups (12.2% vs. 10.8% in Interfant'99, 11 11.2% in MLL-10, 5 and 16.3% in Interfant'06 4 ).…”

“…CNS leukemia (CNS-3 status) is always considered a strong adverse prognostic factor in pediatric ALL, [19][20][21][22] leading to the additional application of CNS-directed therapy. 23,24 The incidence of CNS leukemia in infants with ALL is higher 1,4 than that in older children, and it has been successfully used for the definition of high risk (HR) in recent studies.…”

Flow Cytometric Detection of Malignant Blasts in Cerebrospinal Fluid: A Biomarker of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia

“…CNS involvement is associated with a number of high-risk characteristics, including infant age, T-cell lineage, hyperleukocytosis, and specific chromosomal aberrations in B-ALL, such as rearrangements of the KMT2A gene, t(9;22)[BCR-ABL1] and t(1;19)[TCF3-PBX1] [ 14 ]. Leukemic cells are disseminated to the CNS early in the course of the disease, and with current diagnostic techniques CNS involvement is detected in approximately 10% of patients at diagnosis [ 3 , 4 , 15 , 16 ].…”

“…In addition, not all patients who are CNS-positive at diagnosis develop CNS relapse. Due to the poor prognostic value of current CNS classifications, all patients with ALL receive CNS-directed therapy, consisting of intrathecal chemotherapy, systemic high-dose chemotherapy and, in some cases, cranial irradiation [ 14 ]. These treatments are associated with acute and chronic neurotoxicity, leading to a greater risk of permanent cognitive and neuroendocrine impairments [ 8 , 9 , 17 ].…”

“…CNS leukemia is diagnosed if at least one blast cell is observed on cytospin. Patients without CNS involvement are classified as CNS1 (<5 leukocytes/µL CSF with no blasts on cytospin) and patients with CNS involvement as CNS2 (<5 leukocytes/µL CSF with blasts on cytospin) or CNS3 (≥5 leukocytes/µL CSF with blasts on cytospin and/or clinical signs of CNS involvement), depending of the level of CNS infiltration [ 14 ]. Clinical signs of CNS leukemia include various neurological symptoms, such as cranial nerve palsy, intracranial mass on MRI or retinal involvement.…”