Clinical significance of occult central nervous system disease in adult acute lymphoblastic leukemia: A multicenter report from the Campus ALL Network

M.I.D. Principe, E. Buzzatti, A. Piciocchi, F. Forghieri, M. Bonifacio, F. Lessi, S. Imbergamo, E. Orciuolo, G. Rossi, N. Fracchiolla, S. Trappolini, B. Neri, C. Sarlo, P. Zappasodi, M. Dargenio, M. Cefalo, M.A. Irno-Consalvo, C. Conti, G. Paterno, G. De AngelisM. Sciumè, I.D. Starza, A. Venditti, R. Foà, A.R. Guarini

Research output: Contribution to journalArticlepeer-review

Abstract

In acute lymphoblastic leukemia (ALL), flow cytometry (FCM) detects leukemic cells in patients' cerebrospinal fluid (CSF) more accurately than conventional cytology (CC). However, the clinical significance of FCM positivity with a negative cytology (i.e., occult central nervous system [CNS] disease) is not clear. In the framework of the national Campus ALL program, we retrospectively evaluated the incidence of occult CNS disease and its impact on outcome in 240 adult patients with newly diagnosed ALL. All CSF samples were investigated by CC and FCM. The presence of ≥10 phenotypically abnormal events, forming a cluster, was considered to be FCM positivity. No CNS involvement was documented in 179 patients, while 18 were positive by modified conventional morphology with CC and 43 were occult CNS disease positive. The relapse rate was significantly lower in CNS disease negative patients and the disease-free and overall survival (OS) were significantly longer in CNS disease negative patients than in those with manifest or occult CNS disease positivity. In multivariate analysis, the status of manifest and occult CNS disease positivity was independently associated with a worse OS. In conclusion, we demonstrate that in adult ALL patients at diagnosis FCM can detect occult CNS disease at high sensitivity and that the status of occult CNS disease positivity is associated with an adverse outcome. (Registered at clinicaltrials.gov identifier: NCT03803670).

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalHaematologica
Volume106
Issue number1
DOIs
Publication statusPublished - 2021

Keywords

  • CD19 antibody
  • CD20 antigen
  • common acute lymphoblastic leukemia antigen
  • cytarabine
  • dexamethasone
  • methotrexate
  • methylprednisolone
  • steroid
  • acute lymphoblastic leukemia
  • adult
  • aged
  • allogeneic stem cell transplantation
  • Article
  • cancer chemotherapy
  • cancer mortality
  • cancer prevention
  • cancer recurrence
  • cancer survival
  • central nervous system
  • central nervous system disease
  • cerebrospinal fluid
  • cerebrospinal fluid analysis
  • clinical outcome
  • cytogenetics
  • cytology
  • disease free survival
  • erythrocyte count
  • female
  • flow cytometry
  • follow up
  • human
  • incidence
  • lactate dehydrogenase blood level
  • leukocyte count
  • lumbar puncture
  • major clinical study
  • male
  • multiple cycle treatment
  • overall survival
  • phenotype
  • protein cerebrospinal fluid level
  • recurrence risk
  • retrospective study
  • treatment response
  • clinical trial
  • multicenter study
  • recurrent disease
  • Adult
  • Central Nervous System Diseases
  • Flow Cytometry
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Recurrence
  • Retrospective Studies

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