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Immunoreactive beta-endorphin levels in cerebrospinal fluid of children with acute lymphoblastic leukemia: relationship with glucocorticoid therapy and neurological complications

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Abstract

Neurological disorders, such as seizures, are not infrequently associated with antileukemic therapy. It has been hypothesized that a disrupted peptidergic transmission between neurons could be the cellular basis of the neurological dysfunction. Since endogenous opioids have been recently found to alter neuronal function and possess anticonvulsant properties, the cerebrospinal fluid (CSF) immunoreactive beta-endorphin levels in children with Acute Lymphoblastic Leukemia (ALL) during chemotherapy and cranial irradiation have been studied. Twenty-seven children, 2 at low, 20 at medium and 5 with high risk ALL, undergoing prophylactic treatment for meningeal leukemia, entered the study. Sequential lumbar punctures with introduction of MTX combined with oral prednisone therapy were performed; each lumbar puncture sample was collected and assayed for immunoreactive beta-endorphin. All the patients studied showed a biphasic profile of the peptide with the minimum levels reached during the induction (days 14–28) and the maximum levels detected at the end of the intensification chemotherapy (days 49–55). In the 3 groups the betaendorphin decrease corresponded to the period of prednisone therapy; the increase was concomitant with the suspension of oral glucocorticoids. 3 patients showed tonic-clonic seizures which coincided with the lowest cerebrospinal fluid betaendorphin levels and, in the follow-up, 13 out of 27 patients displayed EEG abnormalities. From these findings a relationship between cerebrospinal fluid beta-endorphin concentrations and neuronal excitability in patients with ALL can be suggested. It is also evidenced that oral glucocorticoid therapy has profound inhibitory effects on central beta-endorphin levels.

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Abbreviations

CSF:

Cerebrospinal fluid

B-EP:

Beta-endorphin

ALL:

Acute Lymphoblastic Leukemia

LP:

Lumbar puncture

i.t.:

Intrathecal

EEG:

Electroencephalogram

CNS:

Central Nervous System

MTX:

Methotrexate

VCR:

Vincristin

PDN:

Prednisone

L-Ase:

L-Asparaginase

6-MP:

6-Mercaptopurine

DNR:

Daunorubicin

RIA:

Radio Immuno Assay

FAB:

French American British

CCG:

Children Cancer Group

AIEOP:

Associazione Italiana di Ematologia e Oncologia Pediatrica

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Authors and Affiliations

  1. Istituto di Clinica Pediatrica, 00161, Roma, Italy

    P. Iannetti MD & C. Imperato

  2. Cattedra di Andrologia, Università di Roma “La Sapienza”, 00161, Roma, Italy

    A. Fabbri, S. Ulisse & A. Isidori

  3. Cattedra di Ematologia, Università di Roma “La Sapienza”, 00161, Roma, Italy

    G. Meloni, M. L. Moleti & F. Mandelli

Authors
  1. P. Iannetti MD
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  2. A. Fabbri
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  3. G. Meloni
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  4. M. L. Moleti
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  5. S. Ulisse
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  6. F. Mandelli
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  7. A. Isidori
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  8. C. Imperato
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Supported in part by grant n. 85.00479.04 C.N.R. Italy

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Iannetti, P., Fabbri, A., Meloni, G. et al. Immunoreactive beta-endorphin levels in cerebrospinal fluid of children with acute lymphoblastic leukemia: relationship with glucocorticoid therapy and neurological complications. J Endocrinol Invest 12, 623–629 (1989). https://doi.org/10.1007/BF03350022

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  • DOI: https://doi.org/10.1007/BF03350022

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