Immunophenotyping of the cerebrospinal fluid as a prognostic factor at diagnosis of acute lymphoblastic leukemia in children and adolescents

Abstract

This study aimed at evaluating the use of immunophenotyping (IMP) in the identification of blast cells in the cerebrospinal fluid (CSF) of children and adolescents with acute lymphoblastic leukemia (ALL). Sixty-seven patients aged 18 years or younger were included. Fifty-five CSF samples were analyzed at initial diagnosis and 17 at the time of relapse. A cytological analysis (CA) was performed in all 72 samples, while IMP was done in 63. Blasts were identified in only three samples by CA, whereas all three samples were found negative by IMP, one of which had no isolation of nucleated cells after centrifugation. Among the samples analyzed by IMP, 11 showed a positive blast count, two of which had been inconclusive using CA. No equivalence was found between CA and IMP results (p = 0.55). CSF IMP positivity was not associated with other risk factors for ALL relapse. Among the 55 patients included at the time of diagnosis of ALL, eight relapsed during follow-up. Considering the cases of central nervous system (CNS) relapse, one of the patients belonged to the CSF IMP-positive group (11%) at diagnosis, and the other two cases, to the IMP-negative (5%) group. Detection of CSF blast cells using IMP was associated with a worse overall (p < 0.0001) and event-free survival (p < 0.0001). These results show that CSF IMP may be a useful additional method to conventional CA in the diagnosis of CNS involvement in ALL, and for the identification of high-risk subgroups that would benefit from an intensified therapy.

ESCCA/ISCCA protocol for the analysis of cerebrospinal fluid by multiparametric flow‐cytometry in hematological malignancies

“…Popov et al (2019) used a 4–6 color antibody combination based on immunophenotype of leukemic cells as determined at initial blast cells characterization including CD19/CD10/CD34/CD45 for the majority of BCP‐ALL and CD7/CD3/CD5/CD2/CD99/CD45 for T‐ALL. In B‐ALL, a similar combination was used by Cancela et al (2017). Recently, 2871 CSF samples from 357 adult ALL were retrospectively analyzed.…”

Recent Advances in Camel Immunology

“…Age-related changes of innate and adaptive cellular immune responses have been described for different species (191,192). The immaturity of newborn immune cells was linked to a higher susceptibility to infectious diseases and higher mortality rates during the early weeks after birth (191,(193)(194)(195)(196)(197)(198)(199)(200). As in other ruminants, camel newborns and adult camels differ significantly regarding their leukogram pattern, phenotype and functionality of blood leukocyte subpopulations (201).…”

Central nervous system (CNS) involvement has an adverse impact on survival in newly diagnosed adult acute lymphoblastic leukemia (ALL) assessed by flow cytometry

“…However, cytology relies solely on the observer's experience and ability to distinguish pathological cells from normal lymphocytes. In the past, the usefulness of flow cytometry had been debated in terms of whether its sensitivity was superior in the detection of early infiltration and whether its use could potentially impact patient prognosis and management [1][2][3][4][8][9][10][11][12][13][14][15]. In this observational study conducted with data obtained in a reference center in Mexico, we analyzed the impact of central nervous system infiltration detected by flow cytometry, on overall survival and event-free survival.…”

“…The treatment of patients that relapse or have newly diagnosed ALL with CNS involvement is a challenge, regardless of the geographic location, socioeconomic factors, or the proximity to an experienced reference center. Different strategies have been developed including radiotherapy, specific neurotrophic chemotherapy (cytarabine or methotrexate), intrathecal chemotherapy, or any combination of the above, and no standard of care has been clearly established [10,11]. Even newer strategies such as monoclonal antibodies or CART-cells have yielded poor results in these groups of patients [32][33][34][35][36][37][38][39].…”