Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Diseases, Lymphoid Malignancies
The electronic medical records of all consecutive pediatric patients diagnosed with B-ALL at Children’s Hospital Los Angeles (CHLA) from September 2008 to December 2019 were reviewed. CSF WBC count and blast involvement were used to calculate CNS status. Blast involvement was determined by one or more pathologists per case by morphologic review of cytocentrifuged CSF material. The patients were divided into two cohorts, one before (cohort A) and one after (cohort B) the COG AALL0932 protocol change (May 20, 2016). Differences between cohorts were evaluated via Fisher’s exact test and Wilcoxon rank sum test. All tests were two-sided, except for CNS2 status, and significance level was set a priori at 0.05.
During the study period, 391 patients were diagnosed with B-ALL at CHLA. These included 192 patients prior to the CNS status-based therapeutic change (cohort A) and 199 patients after the therapeutic change (cohort B). The incidence of CNS2 status was higher in cohort B (20%) than in cohort A (13%) (p=0.052). Conversely, the incidence of CNS1 status was lower in cohort B (77%) than in cohort A (85%), while the incidence of CNS3 was similar before (5%) and after (4%) the protocol change. There were no differences between the cohorts in patient age at diagnosis [cohort A: mean age 8.91 years (SD 5.67 years) vs. cohort B: mean age 8.10 (SD 5.62 years); p=0.20], sex (cohort A: 59.9% male vs. cohort B: 58.8% male; p=0.80), or ethnicity (cohort A: 76.0% Hispanic vs. cohort B: 67.7% Hispanic; p=0.09).
These data suggest that the incidence of CNS2 status in pediatric patients with B-ALL at our institution was higher after (20%) than before (13%) the COG protocol changes that began treating CNS2 patients more intensively than CNS1 patients. In addition to increased frequency of intrathecal chemotherapy, in the ongoing frontline COG standard-risk ALL trial, patients with CNS2 status and neutral cytogenetics are upstaged to higher-risk therapy irrespective of end-induction response. A limitation of this study is that pathologist reviewers of CSF cytospin morphology at the time of CNS assignment differed during the two time periods, such that an observational bias cannot be entirely excluded. Notably, flow cytometry – a more sensitive methodology than cytospin morphology for detection of leukemic cells in CSF material – was not used in these cohorts, but increasingly widespread adoption of such techniques may further increase the incidence of CNS2, including in patients who would otherwise have been diagnosed with CNS1 disease (by cytospin morphology) and as such may be overtreated. Future directions of our study include examination of clinical outcome as well as recent (2021-present) patterns of flow cytometry use in CSF specimens and associated diagnoses of CNS disease in pediatric patients with B-ALL at diagnosis.
Disclosures: No relevant conflicts of interest to declare.
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