Involvement of central nervous system in adult patients with acute myeloid leukemia: Incidence and impact on outcome

Maria Ilaria Del Principe, Francesco Buccisano, Stefano Soddu, Luca Maurillo, Mariagiovanna Cefalo, Alfonso Piciocchi, Maria Irno Consalvo, Giovangiacinto Paterno, Chiara Sarlo, Eleonora De Bellis, Annagiulia Zizzari, Gottardo De Angelis, Daniela Fraboni, Mariadomenica Divona, Maria Teresa Voso, Giuseppe Sconocchia, Giovanni Del Poeta, Francesco Lo-Coco, William Arcese, Sergio AmadoriAdriano Venditti

Research output: Contribution to journalArticle

Abstract

Incidence and effect on outcome of central nervous system (CNS) involvement in adult patients with acute myeloid leukemia (AML) is not clearly defined. To address this issue, 103 consecutive adult patients with newly diagnosed AML, regardless of neurologic symptoms, were submitted to a routine explorative lumbar puncture. Cerebrospinal fluid (CSF) samples were collected from 65 males and 38 females. All 103 CSF samples were examined by conventional cytology (CC) whereas 95 (92%) also by flow cytometry (FCM). At diagnosis, 70 patients (68%) were CNS negative (CNS−), whereas 33 (32%) were CNS positive (CNS+). In 11 of 33 (33%), CNS infiltration was documented either by CC or FCM, in 21 (67%) only by FCM. CNS positivity was significantly associated with a M4-M5 phenotype of the underlying AML (P =.0003) and with high levels of lactate dehydrogenase (P =.006). Overall, 80 of 103 (78%) achieved complete remission with no significant differences between CNS+ and CNS− patients. Five-year disease-free survival and overall survival were found to be shorter in CNS+ patients than in those CNS− (18% vs 50%, P =.006 and 19% vs 46%, P =.02, respectively). In multivariate analysis, CNS status and age were found to affect independently overall survival. In conclusion, the incidence of CNS involvement in adult patients with newly diagnosed AML is higher than expected. Regardless of neurologic symptoms, it should always be searched at diagnosis; CSF samples should routinely be investigated by FCM since a certain proportion of CNS involvements might remain undetected if examination is exclusively CC based.

Original languageEnglish
JournalSeminars in Hematology
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Acute Myeloid Leukemia
Central Nervous System
Incidence
Flow Cytometry
Cell Biology
Cerebrospinal Fluid
Neurologic Manifestations
Spinal Puncture
Survival
L-Lactate Dehydrogenase
Disease-Free Survival
Multivariate Analysis

Keywords

  • Acute myeloid leukemia
  • Central nervous system disease
  • Conventional cytology
  • Flow cytometry
  • Outcome

ASJC Scopus subject areas

  • Hematology

Cite this

Del Principe, M. I., Buccisano, F., Soddu, S., Maurillo, L., Cefalo, M., Piciocchi, A., ... Venditti, A. (Accepted/In press). Involvement of central nervous system in adult patients with acute myeloid leukemia: Incidence and impact on outcome. Seminars in Hematology. https://doi.org/10.1053/j.seminhematol.2018.02.006

Involvement of central nervous system in adult patients with acute myeloid leukemia : Incidence and impact on outcome. / Del Principe, Maria Ilaria; Buccisano, Francesco; Soddu, Stefano; Maurillo, Luca; Cefalo, Mariagiovanna; Piciocchi, Alfonso; Consalvo, Maria Irno; Paterno, Giovangiacinto; Sarlo, Chiara; De Bellis, Eleonora; Zizzari, Annagiulia; De Angelis, Gottardo; Fraboni, Daniela; Divona, Mariadomenica; Voso, Maria Teresa; Sconocchia, Giuseppe; Del Poeta, Giovanni; Lo-Coco, Francesco; Arcese, William; Amadori, Sergio; Venditti, Adriano.

In: Seminars in Hematology, 01.01.2018.

Research output: Contribution to journalArticle

Del Principe, MI, Buccisano, F, Soddu, S, Maurillo, L, Cefalo, M, Piciocchi, A, Consalvo, MI, Paterno, G, Sarlo, C, De Bellis, E, Zizzari, A, De Angelis, G, Fraboni, D, Divona, M, Voso, MT, Sconocchia, G, Del Poeta, G, Lo-Coco, F, Arcese, W, Amadori, S & Venditti, A 2018, 'Involvement of central nervous system in adult patients with acute myeloid leukemia: Incidence and impact on outcome', Seminars in Hematology. https://doi.org/10.1053/j.seminhematol.2018.02.006
Del Principe, Maria Ilaria ; Buccisano, Francesco ; Soddu, Stefano ; Maurillo, Luca ; Cefalo, Mariagiovanna ; Piciocchi, Alfonso ; Consalvo, Maria Irno ; Paterno, Giovangiacinto ; Sarlo, Chiara ; De Bellis, Eleonora ; Zizzari, Annagiulia ; De Angelis, Gottardo ; Fraboni, Daniela ; Divona, Mariadomenica ; Voso, Maria Teresa ; Sconocchia, Giuseppe ; Del Poeta, Giovanni ; Lo-Coco, Francesco ; Arcese, William ; Amadori, Sergio ; Venditti, Adriano. / Involvement of central nervous system in adult patients with acute myeloid leukemia : Incidence and impact on outcome. In: Seminars in Hematology. 2018.
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abstract = "Incidence and effect on outcome of central nervous system (CNS) involvement in adult patients with acute myeloid leukemia (AML) is not clearly defined. To address this issue, 103 consecutive adult patients with newly diagnosed AML, regardless of neurologic symptoms, were submitted to a routine explorative lumbar puncture. Cerebrospinal fluid (CSF) samples were collected from 65 males and 38 females. All 103 CSF samples were examined by conventional cytology (CC) whereas 95 (92{\%}) also by flow cytometry (FCM). At diagnosis, 70 patients (68{\%}) were CNS negative (CNS−), whereas 33 (32{\%}) were CNS positive (CNS+). In 11 of 33 (33{\%}), CNS infiltration was documented either by CC or FCM, in 21 (67{\%}) only by FCM. CNS positivity was significantly associated with a M4-M5 phenotype of the underlying AML (P =.0003) and with high levels of lactate dehydrogenase (P =.006). Overall, 80 of 103 (78{\%}) achieved complete remission with no significant differences between CNS+ and CNS− patients. Five-year disease-free survival and overall survival were found to be shorter in CNS+ patients than in those CNS− (18{\%} vs 50{\%}, P =.006 and 19{\%} vs 46{\%}, P =.02, respectively). In multivariate analysis, CNS status and age were found to affect independently overall survival. In conclusion, the incidence of CNS involvement in adult patients with newly diagnosed AML is higher than expected. Regardless of neurologic symptoms, it should always be searched at diagnosis; CSF samples should routinely be investigated by FCM since a certain proportion of CNS involvements might remain undetected if examination is exclusively CC based.",
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AU - Del Principe, Maria Ilaria

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AU - Soddu, Stefano

AU - Maurillo, Luca

AU - Cefalo, Mariagiovanna

AU - Piciocchi, Alfonso

AU - Consalvo, Maria Irno

AU - Paterno, Giovangiacinto

AU - Sarlo, Chiara

AU - De Bellis, Eleonora

AU - Zizzari, Annagiulia

AU - De Angelis, Gottardo

AU - Fraboni, Daniela

AU - Divona, Mariadomenica

AU - Voso, Maria Teresa

AU - Sconocchia, Giuseppe

AU - Del Poeta, Giovanni

AU - Lo-Coco, Francesco

AU - Arcese, William

AU - Amadori, Sergio

AU - Venditti, Adriano

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N2 - Incidence and effect on outcome of central nervous system (CNS) involvement in adult patients with acute myeloid leukemia (AML) is not clearly defined. To address this issue, 103 consecutive adult patients with newly diagnosed AML, regardless of neurologic symptoms, were submitted to a routine explorative lumbar puncture. Cerebrospinal fluid (CSF) samples were collected from 65 males and 38 females. All 103 CSF samples were examined by conventional cytology (CC) whereas 95 (92%) also by flow cytometry (FCM). At diagnosis, 70 patients (68%) were CNS negative (CNS−), whereas 33 (32%) were CNS positive (CNS+). In 11 of 33 (33%), CNS infiltration was documented either by CC or FCM, in 21 (67%) only by FCM. CNS positivity was significantly associated with a M4-M5 phenotype of the underlying AML (P =.0003) and with high levels of lactate dehydrogenase (P =.006). Overall, 80 of 103 (78%) achieved complete remission with no significant differences between CNS+ and CNS− patients. Five-year disease-free survival and overall survival were found to be shorter in CNS+ patients than in those CNS− (18% vs 50%, P =.006 and 19% vs 46%, P =.02, respectively). In multivariate analysis, CNS status and age were found to affect independently overall survival. In conclusion, the incidence of CNS involvement in adult patients with newly diagnosed AML is higher than expected. Regardless of neurologic symptoms, it should always be searched at diagnosis; CSF samples should routinely be investigated by FCM since a certain proportion of CNS involvements might remain undetected if examination is exclusively CC based.

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