Case Report
Experience using Imatinib and then Nilotinib, as second line, in patient with chronic myeloid leukemia and previous bariatric surgery. A case report
Renato Centronea,
, Marcelo Bellessoa, Debora Bonitob, Daniela Diasa, Rodrigo Santuccia, Milton Aranhaa, Adelson Alvesa
Autor para correspondência
rtcentrone@ig.com.br
Corresponding author at: Instituto Hemomed de Oncologia e Hematologia, Av. Arnolfo Azevedo, 108, Pacaembu, São Paulo, SP CEP: 01236-030, Brazil.
Corresponding author at: Instituto Hemomed de Oncologia e Hematologia, Av. Arnolfo Azevedo, 108, Pacaembu, São Paulo, SP CEP: 01236-030, Brazil.
Lido
3774
Vezesque se leu este artigo
1434
Total PDF
2340
Total HTML
Compartilhar estatÃsticas
array:24 [ "pii" => "S2531137919301622" "issn" => "25311379" "doi" => "10.1016/j.htct.2019.09.003" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "3091" "copyright" => "Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular" "copyrightAnyo" => "2019" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Hematol Transfus Cell Ther. 2020;42:373-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 133 "formatos" => array:3 [ "EPUB" => 20 "HTML" => 69 "PDF" => 44 ] ] "itemSiguiente" => array:19 [ "pii" => "S2531137919301713" "issn" => "25311379" "doi" => "10.1016/j.htct.2019.10.005" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "3100" "copyright" => "Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Hematol Transfus Cell Ther. 2020;42:376-80" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 51 "formatos" => array:3 [ "EPUB" => 13 "HTML" => 17 "PDF" => 21 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case Report</span>" "titulo" => "Thrombotic thrombocytopenic purpura presenting as recurrent thrombocytopenia in a young female — A case report" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "376" "paginaFinal" => "380" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1722 "Ancho" => 2175 "Tamanyo" => 232012 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Brain MRI with venogram showing acute non-hemorrhagic infarct in the left parietooccipital region and the computed tomography (CT) venogram showed a subacute infarct in the left middle cerebral artery (MCA) territory.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sri Gayathri Shanmugam, Nagarajan Priyathersini, Srikanth Muralikrishnan, Archana Balasubramanian" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Sri Gayathri" "apellidos" => "Shanmugam" ] 1 => array:2 [ "nombre" => "Nagarajan" "apellidos" => "Priyathersini" ] 2 => array:2 [ "nombre" => "Srikanth" "apellidos" => "Muralikrishnan" ] 3 => array:2 [ "nombre" => "Archana" "apellidos" => "Balasubramanian" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531137919301713?idApp=UINPBA00005G" "url" => "/25311379/0000004200000004/v3_202011290726/S2531137919301713/v3_202011290726/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2531137919301440" "issn" => "25311379" "doi" => "10.1016/j.htct.2019.08.004" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "3088" "copyright" => "Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Hematol Transfus Cell Ther. 2020;42:365-72" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 171 "formatos" => array:3 [ "EPUB" => 24 "HTML" => 100 "PDF" => 47 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Serologic strategy in detecting <span class="elsevierStyleItalic">RHD</span> altered alleles in Brazilian blood donors" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "365" "paginaFinal" => "372" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1401 "Ancho" => 2163 "Tamanyo" => 140043 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Comparison of reactivities using –D lgM clones with weak and partial D variants The degree of reactivity is reported according to the agglutination intensity.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rosangela Duarte de Medeiros Person, Carine Prisco Arnoni, Janaína Guilhem Muniz, Tatiane Aparecida de Paula Vendrame, Flavia Roche Moreira Latini, Afonso José Pereira Cortez, Jordão Pellegrino, Lilian Maria de Castilho" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Rosangela Duarte de Medeiros" "apellidos" => "Person" ] 1 => array:2 [ "nombre" => "Carine Prisco" "apellidos" => "Arnoni" ] 2 => array:2 [ "nombre" => "Janaína Guilhem" "apellidos" => "Muniz" ] 3 => array:2 [ "nombre" => "Tatiane Aparecida de Paula" "apellidos" => "Vendrame" ] 4 => array:2 [ "nombre" => "Flavia Roche Moreira" "apellidos" => "Latini" ] 5 => array:2 [ "nombre" => "Afonso José Pereira" "apellidos" => "Cortez" ] 6 => array:3 [ "nombre" => "Jordão" "apellidos" => "Pellegrino" "sufijo" => "Jr" ] 7 => array:2 [ "nombre" => "Lilian Maria de" "apellidos" => "Castilho" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531137919301440?idApp=UINPBA00005G" "url" => "/25311379/0000004200000004/v3_202011290726/S2531137919301440/v3_202011290726/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case Report</span>" "titulo" => "Experience using Imatinib and then Nilotinib, as second line, in patient with chronic myeloid leukemia and previous bariatric surgery. A case report" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "373" "paginaFinal" => "375" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Renato Centrone, Marcelo Bellesso, Debora Bonito, Daniela Dias, Rodrigo Santucci, Milton Aranha, Adelson Alves" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Renato" "apellidos" => "Centrone" "email" => array:1 [ 0 => "rtcentrone@ig.com.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Marcelo" "apellidos" => "Bellesso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Debora" "apellidos" => "Bonito" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Daniela" "apellidos" => "Dias" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Rodrigo" "apellidos" => "Santucci" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Milton" "apellidos" => "Aranha" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Adelson" "apellidos" => "Alves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Instituto Hemomed de Oncologia e Hematologia, São Paulo, SP, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Faculdade de Medicina do ABC, São Paulo, SP, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author at</span>: Instituto Hemomed de Oncologia e Hematologia, Av. Arnolfo Azevedo, 108, Pacaembu, São Paulo, SP CEP: 01236-030, Brazil." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic myeloid leukemia (CML) has become a model of success in the history of hematology. That is due to the possibility of discovering and monitoring the molecular basis of the disease and blocking it by employing tyrosine kinase inhibitors (TKIs).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> In the beginning of the XXI century, chemotherapy and the recombinant interferon-alpha were overcome by the efficiency of the TKIs in chronic-phase (CP) CML patients. Approximately 80% of the patients presenting CP-CML treated with imatinib achieved complete cytogenetic remission (CCR). Moreover, these patients also present extraordinary long survival rates. Firstly, imatinib demonstrated that a fatal cancer could become a chronic comorbidity. Soon after the first generation of TKIs, owing to the development of imatinib-resistance, other TKIs were developed, such as: dasatinib, nilotinib, bosutinib and ponatinib.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The TKI era has modified the CML treatment and its outcomes consensus was reached regarding rational goals to define optimal response, based on time to CCR and molecular response (MR).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> Thus, it was possible to adopt intervention patterns for patients who failed to respond adequately to regular treatment.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Currently, optimal response is considered when patients achieve major molecular response (MMR), BCR-ABL1<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.1% on the International Scale (IS) within 12 months of the TKI treatment.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3</span></a> Molecular response levels have been related to the best control of the disease and long survival. Nilotinib has displayed better efficacy than imatinib in achieving MMR within two years.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Deep molecular response (DMR), defined as a 4.5 log reduction (IS), has been the real target response in order to promote the discontinuation of the TKI.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> Several studies have shown that it is feasible to discontinue treatment after at least two years of DMR. On the other hand, it is important to know that treatment-free remission ranges from 48 to 67%.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In Brazil, imatinib is the TKI generally used in the first-line treatment for patients with CP-CML. Although the importance of imatinib has been recognized, 20–30% of the patients discontinue treatment because of imatinib-related unsatisfactory response, resistance or toxicity.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> Nilotinib has shown significant improvements (45% achieved CCR) for patients who are resistant or intolerant to imatinib.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> Instead of evaluating solely the imatinib treatment efficacy, another aspect of patient monitoring comprises the imatinib-related adverse events (IRAEs). Today, due to the long-lasting character of treatments, not only adverse events grade III–IV have been the reason to switch to other TKIs, but also mild and moderate adverse events that are linked with the quality of life.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> The IRAEs from imatinib are frequent<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> and more predominant, compared to nilotinib.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> It has been reported that it is possible to reduce or resolve the IRAEs after three months of shifting to nilotinib.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> Thus, it is important that Brazilian patients be closely monitored, with analysis of the quality of life, adherence and their relation to IRAEs. Consequently, for patients treated with imatinib, switching to nilotinib has been indicated, due to the resistance to imatinib, failed optimal response and intolerance.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Our purpose, therefore, is to describe the importance of switching the treatment, in an unknown scenario of previous bariatric surgery, to the optimal response by imatinib, however with poor quality of life due to chronic IRAEs.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In September 2014, a 67-year-old female patient presented with leukocytosis in a routine blood count of leukocytes at 15.9<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L, with neutrophilic predominance and 570,000<span class="elsevierStyleHsp" style=""></span>platelets/mm<span class="elsevierStyleSup">3</span>. She was asymptomatic and no splenomegaly was palpable. Cytogenetic analysis showed 46, XX, t(9;22) (q34.1;q11,2) [16]/46, XX[4]. The patient was diagnosed with PC-CML, classified as intermediate risk by the Sokal index. The patient's medical history included Roux-en-Y laparoscopic gastric bypass for weight loss in 2002, arterial hypertension and hypothyroidism.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The Conventional dose of imatinib of 400<span class="elsevierStyleHsp" style=""></span>mg/day was initiated in December 2014. After six months, the patient achieved CCR and BCR-ABL<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>1% on the IS. In October 2015, the DMR was confirmed.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Despite good laboratorial response, she presented some clinical complaints. Her quality of life was harmed by considerable IRAEs: muscle cramps grade II, nausea grade II and pruritus grade I. Due to the DMR, her attending physician opted to maintain the imatinib treatment. However, in October 2016, blisters grade II appeared on both legs. Therefore, the doctor decided to switch to nilotinib as a second-line treatment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In November 2016, nilotinib 400<span class="elsevierStyleHsp" style=""></span>mg twice/day was initiated, aspiring to reduce the IRAEs. All of the symptoms were resolved within six months, as she remained in DMR. Currently, her status remains asymptomatic and in DRM.</p><p id="par0050" class="elsevierStylePara elsevierViewall">On that account, this case demonstrates that switching to nilotinib may fade chronic IRAEs, as well as conserving the DMR in a patient with bariatric surgery.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">This case presented adequate treatment adherence and optimal response, despite evidencing poor quality of life.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Although imatinib has shown to be safe and effective in the history of CML, chronic mild and moderate IRAEs are not rare.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> In this case, her mild chronic IRAEs were frequent, since the IRIS trial revealed a high frequency of nausea, muscle cramps, and pruritus<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Chronic mild and moderate IRAEs may negatively influence the quality of life and impact adherence to the imatinib therapy, which leads to less desirable outcomes.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Changing from imatinib to another tyrosine kinase inhibitor (TKI) may enhance tolerability and quality of life. The nilotinib treatment, compared to imatinib, exhibited less frequency of nausea, muscle cramps, vomiting and diarrhea.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> In addition, the ENRICH study demonstrated that switching to nilotinib reduced 84.6%, and resolved 62.9%, of chronic IRAEs. Switching to nilotinib revealed to be acceptably safe and potent for molecular response<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Mild skin reactions are relatively frequent, ranging from 7% to 21% in patients treated with imatinib. Skin rashes are relatively common and may be resolved with oral steroids.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> Cutaneous reactions to imatinib seem to be correlated with the dose.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> The imatinib-related blister, a rare skin toxicity, is not well understood. However, the case of a female with a recurrent blister 1.5 years after initiating the imatinib therapy for a gastrointestinal stromal tumor (GIST) has been described. A laminin and collagen IV loss along the dermoepidermal junction was observed, suggesting that, in susceptible patients, imatinib diminishes the synthesis of laminin and collagen IV, resulting in a blister.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> In our case, the blisters were resolved after switching to nilotinib.</p><p id="par0070" class="elsevierStylePara elsevierViewall">This case study presented poor quality of life due to some IRAEs, while still displaying optimal response, but she did not qualify for the cessation of the TKI. Thus, switching to nilotinib was a reasonable option, in spite of the gastroplasty. There have been few studies regarding TKIs in patients with a history of bariatric surgery. Pavlowski et al. demonstrated in a case report that the imatinib concentration decreased 40–60% after sleeve gastrectomy. On the other hand, a patient remained in molecular response<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> in a similar scenario in which Yassin et al. described a female patient treated with dasatinib who lost hematological response after a sleeve gastrectomy, with negative mutation analysis. After switching the treatment to imatinib, she achieved an adequate response. In another case, a male was diagnosed with CML two years after undergoing a sleeve gastrectomy. The treatment started with nilotinib 300<span class="elsevierStyleHsp" style=""></span>mg q12<span class="elsevierStyleHsp" style=""></span>h, but the patient did not achieve a cytogenetic and molecular response, presenting a negative mutation test. After switching the treatment to imatinib, he achieved a molecular response.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Liu and Artz observed the reduction of imatinib levels from 956 to 156<span class="elsevierStyleHsp" style=""></span>ng/mL after a Roux-en-Y gastric bypass in a study subject. This patient did not achieve a DMR by employing imatinib. Nilotinib was described as the second-line treatment, but no outcome from that treatment has been described.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> Even though these cases are anecdotal, evidencing failure in the second-generation TKIs, our case report expressed the successful choice of nilotinib treatment, applying a 400<span class="elsevierStyleHsp" style=""></span>mg q12<span class="elsevierStyleHsp" style=""></span>h posology after the DMR, achieved by imatinib.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Therefore, this case report presents common IRAEs, which determined a poor quality of life, in contrast with no loss of adherence regarding the DMR (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). This case deserves to be registered in order to emphasize that a patient was successfully treated with nilotinib 400<span class="elsevierStyleHsp" style=""></span>mg q12<span class="elsevierStyleHsp" style=""></span>h, even while presenting a Roux-en-Y gastric bypass. Such treatment strategy presented maintenance of the DMR and resolution of IRAEs, including the gastrointestinal adverse events, even when administering the nilotinib posology twice a day.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Discussion" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-07-01" "fechaAceptado" => "2019-09-23" "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><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">IRAE \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IRIS trial<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a>IRAE all grade<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>551 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ENRICH study<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a>Resolved IRAEAfter 3 months of switching to nilotinib<span class="elsevierStyleItalic">n</span> (%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case reportStatus of IRAE after switching to nilotininb \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">Muscle cramps \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.3% \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (100%) \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">Resolved \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">Nausea \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.7% \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (93.7%) \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">Resolved \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">Pruritus \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1% \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (66.6%) \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">Resolved \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2441387.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Imatinib-related adverse events (IRAEs) presented in this case: incidence, rate of resolution after switching to nilotinib.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imatinib compared with interferon and lowdose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.G. O’Brien" 1 => "F. Guilhot" 2 => "R.A. Larson" 3 => "I. Gathmann" 4 => "M. Baccarani" 5 => "F. Cervantes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa022457" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2003" "volumen" => "348" "numero" => "11" "paginaInicial" => "994" "paginaFinal" => "1004" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12637609" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Baccarani" 1 => "J. Cortes" 2 => "F. Pane" 3 => "D. Niederwieser" 4 => "G. Saglio" 5 => "J. Apperley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2009.25.0779" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "6041" "paginaFinal" => "6051" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19884523" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. O’Brien" 1 => "E. Berman" 2 => "H. Borghaei" 3 => "D.J. Deangelo" 4 => "M.P. Devetten" 5 => "S. Devine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.6004/jnccn.2009.0065" "Revista" => array:6 [ "tituloSerie" => "J Natl Compr Canc Netw" "fecha" => "2009" "volumen" => "7" "paginaInicial" => "984" "paginaFinal" => "1023" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19878641" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.M. Kantarjian" 1 => "A. Hochhaus" 2 => "G. Saglio" 3 => "C. De Souza" 4 => "I.W. Flinn" 5 => "L. Stenke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(11)70201-7" "Revista" => array:7 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2011" "volumen" => "12" "numero" => "9" "paginaInicial" => "841" "paginaFinal" => "851" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21856226" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "When to stop tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P. Laneuville" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11864-018-0532-2" "Revista" => array:6 [ "tituloSerie" => "Curr Treat Options Oncol" "fecha" => "2018" "volumen" => "19" "numero" => "3" "paginaInicial" => "15" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29520446" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.M. Lucas" 1 => "L. Wang" 2 => "G.M. Austin" 3 => "K. Knight" 4 => "S.J. Watmough" 5 => "K.H. Shwe" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Leukemia" "fecha" => "2008" "volumen" => "94" "paginaInicial" => "1362" "paginaFinal" => "1367" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.J. Giles" 1 => "P.D. le Coutre" 2 => "J. Pinilla-Ibarz" 3 => "R.A. Larson" 4 => "N. Gattermann" 5 => "O.G. Ottmann" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Leukemia" "fecha" => "2013" "volumen" => "27" "numero" => "1" "paginaInicial" => "107" "paginaFinal" => "112" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GIMEMA. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Efficace" 1 => "M. Baccarani" 2 => "M. Breccia" 3 => "G. Alimena" 4 => "G. Rosti" 5 => "F. Cottone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2011-04-347575" "Revista" => array:7 [ "tituloSerie" => "Blood" "fecha" => "2011" "volumen" => "118" "numero" => "17" "paginaInicial" => "4554" "paginaFinal" => "4560" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21750313" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nilotinib versus imatinib for newly diagnosed chronic myeloid leucemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Saglio" 1 => "D.W. Kim" 2 => "S. Issaragrisil" 3 => "P. le Coutre" 4 => "G. Etienne" 5 => "C. Lobo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0912614" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2010" "volumen" => "362" "numero" => "24" "paginaInicial" => "2251" "paginaFinal" => "2259" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20525993" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluating the impact of a switch to nilotinib on imatinib-related chronic low-grade adverse events in patients with CML-CP: the ENRICH study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.E. Cortes" 1 => "J.H. Lipton" 2 => "C.B. Miller" 3 => "L. Busque" 4 => "L.P. Akard" 5 => "J. Pinilla-Ibarz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Lymphoma Myeloma Leuk" "fecha" => "2016" "volumen" => "16" "numero" => "5" "paginaInicial" => "286" "paginaFinal" => "296" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.R. Ibrahim" 1 => "L. Eliasson" 2 => "J.F. Apperley" 3 => "D. Milojkovic" 4 => "M. Bua" 5 => "R. Szydlo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2010-10-309807" "Revista" => array:7 [ "tituloSerie" => "Blood" "fecha" => "2011" "volumen" => "117" "numero" => "14" "paginaInicial" => "3733" "paginaFinal" => "3736" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21346253" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blistering and skin fragility due to imatinib therapy: loss of laminin and collagen iv as a possible cause of cutaneous basement membrane instability" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Mühl" 1 => "J. Ehrchen" 2 => "D. Metze" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/DAD.0000000000001063" "Revista" => array:7 [ "tituloSerie" => "Am J Dermatopathol" "fecha" => "2018" "volumen" => "40" "numero" => "5" "paginaInicial" => "371" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29210715" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imatinib mesylate pharmacokinetics before and after sleeve gastrectomy in a morbidly obese patient with chronic myeloid leucemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Pavlovsky" 1 => "M.J. Egorin" 2 => "D.D. Shah" 3 => "J.H. Beumer" 4 => "S. Rogel" 5 => "S. Pavlovsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1592/phco.29.9.1152" "Revista" => array:7 [ "tituloSerie" => "Pharmacotherapy" "fecha" => "2009" "volumen" => "29" "numero" => "9" "paginaInicial" => "1152" "paginaFinal" => "1156" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19698017" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Second generation tyrosisne kinase inhibitors as upfront therapy in the era of sleeve gastrectomy does it work?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Yassin" 1 => "A. Nashwan" 2 => "N. Kassem" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Blood" "fecha" => "2017" "volumen" => "130" "paginaInicial" => "5360" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduction of imatinib concentration after gastric bypass surgery" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H. Liu" 1 => "A.S. Artz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2009-10-247361" "Revista" => array:5 [ "tituloSerie" => "Blood" "fecha" => "2010" "volumen" => "116" "paginaInicial" => "4948" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20805362" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/25311379/0000004200000004/v3_202011290726/S2531137919301622/v3_202011290726/en/main.assets" "Apartado" => array:4 [ "identificador" => "72898" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case Reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/25311379/0000004200000004/v3_202011290726/S2531137919301622/v3_202011290726/en/main.pdf?idApp=UINPBA00005G&text.app=http://www.htct.com.br/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531137919301622?idApp=UINPBA00005G" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Outubro | 44 | 23 | 67 |
| 2024 Setembro | 60 | 24 | 84 |
| 2024 Agosto | 64 | 61 | 125 |
| 2024 Julho | 37 | 21 | 58 |
| 2024 Junho | 59 | 32 | 91 |
| 2024 Maio | 56 | 33 | 89 |
| 2024 Abril | 34 | 38 | 72 |
| 2024 Março | 44 | 20 | 64 |
| 2024 Fevereiro | 29 | 24 | 53 |
| 2024 Janeiro | 27 | 20 | 47 |
| 2023 Dezembro | 23 | 27 | 50 |
| 2023 Novembro | 39 | 27 | 66 |
| 2023 Outubro | 32 | 34 | 66 |
| 2023 Setembro | 35 | 29 | 64 |
| 2023 Agosto | 18 | 14 | 32 |
| 2023 Julho | 46 | 15 | 61 |
| 2023 Junho | 24 | 13 | 37 |
| 2023 Maio | 40 | 15 | 55 |
| 2023 Abril | 30 | 14 | 44 |
| 2023 Março | 53 | 16 | 69 |
| 2023 Fevereiro | 34 | 11 | 45 |
| 2023 Janeiro | 25 | 9 | 34 |
| 2022 Dezembro | 45 | 23 | 68 |
| 2022 Novembro | 42 | 29 | 71 |
| 2022 Outubro | 38 | 19 | 57 |
| 2022 Setembro | 29 | 43 | 72 |
| 2022 Agosto | 25 | 16 | 41 |
| 2022 Julho | 24 | 24 | 48 |
| 2022 Junho | 21 | 25 | 46 |
| 2022 Maio | 20 | 19 | 39 |
| 2022 Abril | 76 | 21 | 97 |
| 2022 Março | 33 | 27 | 60 |
| 2022 Fevereiro | 19 | 28 | 47 |
| 2022 Janeiro | 23 | 27 | 50 |
| 2021 Dezembro | 27 | 17 | 44 |
| 2021 Novembro | 23 | 35 | 58 |
| 2021 Outubro | 34 | 31 | 65 |
| 2021 Setembro | 33 | 30 | 63 |
| 2021 Agosto | 34 | 43 | 77 |
| 2021 Julho | 34 | 30 | 64 |
| 2021 Junho | 28 | 27 | 55 |
| 2021 Maio | 43 | 59 | 102 |
| 2021 Abril | 100 | 51 | 151 |
| 2021 Março | 47 | 35 | 82 |
| 2021 Fevereiro | 73 | 21 | 94 |
| 2021 Janeiro | 83 | 22 | 105 |
| 2020 Dezembro | 100 | 13 | 113 |
| 2020 Novembro | 100 | 42 | 142 |
| 2020 Outubro | 24 | 12 | 36 |
| 2020 Setembro | 38 | 11 | 49 |
| 2020 Agosto | 32 | 15 | 47 |
| 2020 Julho | 39 | 16 | 55 |
| 2020 Junho | 37 | 22 | 59 |
| 2020 Maio | 44 | 13 | 57 |
| 2020 Abril | 20 | 8 | 28 |
| 2020 Março | 23 | 12 | 35 |
| 2020 Fevereiro | 29 | 16 | 45 |
| 2020 Janeiro | 28 | 19 | 47 |
| 2019 Dezembro | 9 | 7 | 16 |
| 2019 Novembro | 10 | 6 | 16 |
Mostrar tudo
