Blastic plasmacytoid dendritic cell neoplasm. A study of three cases

Sitges, Marta; Vives, Susana; Ribera, Josep-María
doi:10.1016/j.medcle.2019.04.049
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Blastic plasmacytoid dendritic cell neoplasm &#40;BPDCN&#41; is a rare aggressive hemopathy recognized in the 2008 WHO classification&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a> It was first described in 1990 and since then has undergone multiple nomenclature changes&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Represents 0&#46;44&#37; of malignant blood diseases<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> predominantly affecting men in the sixth decade&#44; although some cases have also been described in children&#46; Its diagnosis can be complex and lacks standardized treatment due to its low incidence and the lack of prospective studies&#46; We report three cases diagnosed in one centre who received individualized treatment according to age and functional status&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first patient is a 29-year-old man with cutaneous and central nervous system involvement who received treatment according to the Hyper-CVAD regimen &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; with which he achieved complete response &#40;CR&#41;&#46; Subsequently&#44; he received an allogeneic hematopoietic stem-cell transplantation &#40;AHSCT&#41; after which he remained in CR&#46; The second patient is a 66-year-old man with hepatomegaly&#44; lymphadenopathy&#44; and blasts in peripheral blood&#44; who was treated with a protocol for acute lymphoblastic leukaemia &#40;ALL&#41; for elderly patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; after which he achieved CR&#46; He received an AHSCT and died 3 months later due to septic shock&#46; The third patient is a 79-year-old woman with a several-month history of skin lesions and detection of blasts in peripheral blood 4 months later&#46; She received treatment according to the R-CHOP regimen &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; after which she died due to disease progression&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The treatment of BPDCN is based on retrospective studies with a limited number of cases&#46; Therapeutic regimens for acute myeloblastic leukaemia and ALL are the most widely used &#40;as in cases 1 and 2&#41;&#44; with a high rate of complete responses &#40;41&#8211;100&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> ALL regimens appear to be superior&#44; but the available evidence is weak&#46; Non-Hodgkin&#8217; lymphoma regimens have also been used&#44; which&#44; even though they appear to be less effective&#44; may be the choice in more fragile patients &#40;as occurred in the third patient&#41;&#46; However&#44; the response to treatment is usually short-lived &#40;6&#8211;9 months&#41; with a high relapse rate &#40;33&#8211;100&#37;&#41;&#44; which determines a short overall survival &#40;OS&#41; of 12&#8211;16 months&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The prognosis in relapse is very poor and effective therapeutic options are not available&#46; For this reason&#44; consolidation with AHSCT in the first CR is recommended &#40;as was done in the first two patients in this series&#41;&#46; In a recent multicenter study&#44; patients who received an AHSCT had a 58&#37; probability of OS at 3 years&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> In addition&#44; differences in OS were observed between patients transplanted in the first CR or not &#40;3-year OS of 74&#37; vs&#46; 0&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Autologous transplantation has also been used and&#44; although it seems to have worse outcomes&#44; it could be considered in patients with comorbidities that prevent performing an AHSCT&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">However&#44; it should be taken into account that BPDCN is often diagnosed in elderly patients with comorbidities&#44; who are not candidates for AHSCT or intensive therapy &#40;as occurred in the third patient&#41;&#46; Radiotherapy can be effective in localized disease&#44; but relapse is very common and is therefore reserved for elderly patients who are not candidates for intensive treatment&#46; Systemic treatment is recommended in the rest of the patients&#46; New therapies are being developed to improve first-line and relapse outcomes&#46; SL-401&#44; a recombinant interleukin 3&#945; conjugated to diphtheria toxin has shown a significant rate of overall responses&#44; albeit short-lived&#44; in a phase 1&#47;2 study&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> Other drugs such as venetoclax&#44; bortezomib&#44; or hypomethylating agents are also being studied&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2&#44;3&#44;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion&#44; the available evidence to standardize the treatment of BPDCN is scarce&#46; Various therapeutic options are available&#44; depending on the clinical context&#44; and AHSCT could play an important role in improving long-term results&#46; However&#44; more effective first-line therapeutic strategies are needed to improve treatment outcomes&#44; especially for patients who are not candidates for intensive therapy&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0030" class="elsevierStylePara elsevierViewall">Partially financed with grants <span class="elsevierStyleGrantNumber" refid="gs1">RD12&#47;0036&#47;0029</span> &#40;<span class="elsevierStyleGrantSponsor" id="gs1">Telematic Network for Cooperative Cancer Research&#44; Spain</span>&#41;&#44; <span class="elsevierStyleGrantNumber" refid="gs2">PI14&#47;01971FIS</span> &#40;<span class="elsevierStyleGrantSponsor" id="gs2">Instituto Carlos III&#44; Spain</span>&#41;&#44; and SGR 288 &#40;GRC&#41; of the <span class="elsevierStyleGrantSponsor" id="gs3">CERCA program of the Generalitat de Catalunya &#40;Spain&#41;</span>&#46;</p></span></span>"
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                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leukocytes &#40;&#215;10<span class="elsevierStyleSup">9</span>&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Haemoglobin &#40;g&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">124&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blasts PB &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hyper-CVAD x2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PETHEMA ALL Old-2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CHOP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not rated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AHSCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 months&#44; alive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 months&#44; death from septic shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 months&#44; death due to disease progression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                          "autores" => array:3 [
                            0 => "F&#46; Facchetti"
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                      "doi" => "10.1111/bjh.14146"
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                        "volumen" => "174"
                        "paginaInicial" => "188"
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                        0 => array:2 [
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                          "autores" => array:6 [
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                            3 => "R&#46;V&#46; Raj"
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                            2 => "C&#46; Ahn"
                            3 => "N&#46; Pemmaraju"
                            4 => "B&#46;C&#46; Medeiros"
                            5 => "H&#46;E&#46; Carraway"
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                    0 => array:2 [
                      "doi" => "10.1182/blood-2014-04-566737"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2014"
                        "volumen" => "124"
                        "paginaInicial" => "385"
                        "paginaFinal" => "392"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24859366"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Blastic plasmacytoid dendritic cell neoplasm is dependent on BCL2 and sensitive to venetoclax"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "J&#46; Stephansky"
                            2 => "T&#46; Cai"
                            3 => "G&#46;K&#46; Griffin"
                            4 => "L&#46; Cabal-Hierro"
                            5 => "K&#46; Togami"
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                      "doi" => "10.1158/2159-8290.CD-16-0999"
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                        "tituloSerie" => "Cancer Discov"
                        "fecha" => "2016"
                        "volumen" => "7"
                        "paginaInicial" => "156"
                        "paginaFinal" => "164"
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