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He remained asymptomatic with progression of lymphocytosis for 2 years until he developed progressive lower-limb proximal paresis (of months of progression), without sensory deficit or constitutional symptoms.</p><p id="par0020" class="elsevierStylePara elsevierViewall">After the electromyographic study (compatible with acute phase polyradiculoneuropathy), magnetic resonance imaging ruled out brain and vertebral lesions, and described associated multiple-lymphadenopathy. The immunophenotypic study of cerebrospinal fluid (CSF) was compatible with B-CLL infiltration.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The patient was diagnosed with B-CLL, non-mutated for the heavy chain gene (IGHV), stage II-B with CSF involvement. Treatment was initiated with weekly triple intrathecal therapy (methotrexate 12 mg + cytarabine 30 mg + hydrocortisone 20 mg). After 5 doses, given the persistence of symptomatology and aberrant lymphocytes in the CSF, it was decided to initiate systemic treatment with ibrutinib (420 mg/24 h). After 12 days, progressive improvement was observed until total resolution of symptoms. Currently (24 months later) the patient is on the same treatment with good tolerance and response.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Neurological infiltration in patients with CLL should be suspected in subacute or chronic neurological conditions with multifocal involvement.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The 80 patients in the review by Moazzam et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> coincide with our case both in the mean latency time between CLL diagnosis and neurological manifestations (2.62 years) and in the absence of disease on neuroimaging (only one third showed abnormalities).</p><p id="par0040" class="elsevierStylePara elsevierViewall">The review by Strati et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> studied 4,174 patients with CLL and neurological symptoms and looked at the incidence of CNS infiltration by CLL with CSF flow cytometry (FCM) and brain MRI; 18 (0.4%) had CLL infiltration. Although CSF FCM is necessary in most cases to confirm the diagnosis and is very sensitive (89%) for detecting CLL cells, it has a low specificity (42%) for differentiating between CLL infiltration and other causes.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Wanquet et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> reviewed 30 cases of CNS-infiltrating CLL: 20 patients had never been treated (<span class="elsevierStyleItalic">naive</span>). Of these, 10 were treated with systemic chemotherapy regimens (with/without TIT) and 8 achieved a durable response (33 months: 4–78). In contrast, previously treated (<span class="elsevierStyleItalic">non-naive</span>) patients were treated with systemic regimens (70% with TIT), in which 50% required 3 additional lines (2–7) of treatment. Previously heavily treated patients who received treatment with ibrutinib 4/4 achieved CR.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Recent publications describe the efficacy of ibrutinib (Bruton's tyrosine kinase inhibitor) in inhibiting the proliferation and survival of neoplastic B-cells as well as lymphoid migration to extramedullary tissues, offering new therapeutic possibilities.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Regarding prognosis, both Moazzam et al.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and Strati et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> reported a median latency time between CLL diagnosis and death of 12 months. Wanquet et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> described a 5-year overall survival of 72% in <span class="elsevierStyleItalic">naïve</span> patients and 48% in <span class="elsevierStyleItalic">non-naïve</span> patients; with a 5-year progression-free survival of 43% and 0%, respectively. The 17p deletion was significantly associated with worse progression-free survival: the authors concluded that the prognosis in these cases depends more on the characteristics of the CLL than on the infiltration itself.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In our case, a <span class="elsevierStyleItalic">naïve</span> patient without 17p deletion, the good clinical outcome 24 months after ibrutinib initiation is in line with that described by Wanquet et al.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Because there is no standard protocol for CLL with CNS involvement, it is important to accumulate case series for a better understanding of the disease and the advent of new drugs.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have no financial interests or personal relationships that may have influenced the preparation of this paper.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.C. Hanse" 1 => "M.B. Van’t Veer" 2 => "K. Van Lom" 3 => "M.J. Van den Bent" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00415-008-0710-4" "Revista" => array:7 [ "tituloSerie" => "J Neurol." "fecha" => "2008" "volumen" => "255" "numero" => "6" "paginaInicial" => "828" "paginaFinal" => "830" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18446313" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Central nervous system lymphoma in a patient with chronic lymphocytic leukemia: a case report and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Albakr" 1 => "W. Alhothali" 2 => "P. Samghabadi" 3 => "L. Maeda" 4 => "S. Nagpal" 5 => "A. 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Journal Information
Vol. 161. Issue 8.
Pages 361-362 (October 2023)
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Vol. 161. Issue 8.
Pages 361-362 (October 2023)
Letter to the Editor
Infiltration of the central nervous system in patients with chronic lymphatic leukemia
Infiltración del sistema nervioso central en pacientes con leucemia linfática crónica
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