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Patterns and prognostic impact of CNS infiltration in adults with newly diagnosed acute lymphoblastic leukemia

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Abstract

Acute lymphoblastic leukemia (ALL) is highly associated with central nervous system (CNS) infiltration and can be associated with higher risk of relapse. Conventional cytology (CC) is the traditional method for diagnosing CNS infiltration, although the use of immunophenotyping by flow cytometry (FC) has gained prominence in recent years due to its higher sensitivity. Also, some authors have proposed that CSF contamination by a traumatic lumbar puncture (TLP) could have a clinical impact. This retrospective study accessed the impact of CNS infiltration by CC or FC on overall survival, event-free survival, and relapse rate. In a cohort of 105 newly diagnosed ALL patients, CNS1, CNS2, and CNS3 status were found in 84%, 14%, and 2%, respectively. We found that extramedullary disease at the diagnosis, higher leukocyte counts, and higher blast percentage were associated with a positive CC. Sensitivity and specificity of CC were 53% and 98%, respectively. Three-year overall survival was 42.5%. Conversely, TLP was not associated with a positive CC nor had an impact on relapse rates. In multivariate analysis, a positive CC was associated with an increased relapse rate (HR 2.074, p = 0.037), while its detection by FC did not associate with this endpoint. Survival rates seem to be increasing over the last years by the adoption of a stratified CNS prophylaxis risk strategy. CSF contamination does not represent a major concern according to our report, as it did not increase CNS involvement or relapse rates.

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Division of Hematology and Cell Therapy, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, 01246-000, Brazil

    Luiza Lapolla Perruso, Elvira Velloso, Vanderson Rocha, Eduardo Magalhaes Rego & Wellington Fernandes Silva

  2. Instituto Do Cancer Do Estado de São Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, Cerqueira César, São Paulo, SP, CEP 01246-000, Brazil

    Luiza Lapolla Perruso, Elvira Velloso, Vanderson Rocha, Eduardo Magalhaes Rego & Wellington Fernandes Silva

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by LLP, EMR, and WFS. The first draft of the manuscript was written by WFS, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wellington Fernandes Silva.

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Ethics approval

This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of University of Sao Paulo approved this study (Plataforma Brasil, CAAE 80534117.4.0000.0068, https://plataformabrasil.saude.gov.br).

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Informed consent was waived by IRB for this retrospective study.

Competing interests

The authors declare no competing interests.

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Summary points

• Central nervous disease in acute lymphoblastic leukemia may decrease survival.

• Clinical significance of CSF flow cytometry remains unclear.

• Cytometry is more sensitive, but only positive cytology impacted on relapse rate.

• CSF contamination did not increase CNS disease or relapse rates.

Supplementary Information

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Supplementary file1 (DOCX 20 KB)

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Perruso, L.L., Velloso, E., Rocha, V. et al. Patterns and prognostic impact of CNS infiltration in adults with newly diagnosed acute lymphoblastic leukemia. Ann Hematol 103, 2033–2039 (2024). https://doi.org/10.1007/s00277-023-05609-4

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