array:22 [ "pii" => "S0025775317309090" "issn" => "00257753" "doi" => "10.1016/j.medcli.2017.11.027" "estado" => "S300" "fechaPublicacion" => "2018-11-09" "aid" => "4360" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2018;151:339-44" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 17 "formatos" => array:2 [ "HTML" => 9 "PDF" => 8 ] ] "itemSiguiente" => array:19 [ "pii" => "S002577531730917X" "issn" => "00257753" "doi" => "10.1016/j.medcli.2017.11.033" "estado" => "S300" "fechaPublicacion" => "2018-11-09" "aid" => "4368" "copyright" => "Elsevier España, S.L.U." 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"apellidos" => "Pastor-Torres" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020618304017" "doi" => "10.1016/j.medcle.2018.09.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618304017?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577531730917X?idApp=UINPBA00004N" "url" => "/00257753/0000015100000009/v1_201810220613/S002577531730917X/v1_201810220613/es/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "339" "paginaFinal" => "344" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ying Shen, Aili He, Fangxia Wang, Ju Bai, Jianli Wang, Wanhong Zhao, Wanggang Zhang, Xingmei Cao, Yinxia Chen, Jie Liu, Xiaorong Ma, Hongli Chen, Yuandong Feng, Yun Yang" "autores" => array:14 [ 0 => array:3 [ "nombre" => "Ying" "apellidos" => "Shen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Aili" "apellidos" => "He" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Fangxia" "apellidos" => "Wang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Ju" "apellidos" => "Bai" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Jianli" "apellidos" => "Wang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Wanhong" "apellidos" => "Zhao" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Wanggang" "apellidos" => "Zhang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Xingmei" "apellidos" => "Cao" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Yinxia" "apellidos" => "Chen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "Jie" "apellidos" => "Liu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 10 => array:3 [ "nombre" => "Xiaorong" "apellidos" => "Ma" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 11 => array:3 [ "nombre" => "Hongli" "apellidos" => "Chen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 12 => array:3 [ "nombre" => "Yuandong" "apellidos" => "Feng" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 13 => array:4 [ "nombre" => "Yun" "apellidos" => "Yang" "email" => array:1 [ 0 => "yangyun108@163.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Hematology, Second Affiliated Hospital, Xi’an Jiaotong University, 710004 Xi’an, Shaanxi, China" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "National-Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, 710004 Xi’an, Shaanxi, China" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La adición de factor estimulante de colonias de granulocitos a la quimioterapia de rescate es más efectiva que la quimioterapia de rescate en el tratamiento de la recidiva de la leucemia mieloide aguda" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1284 "Ancho" => 1570 "Tamanyo" => 68342 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Disease-free survival rate of two groups.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic stem cell disorder with an incidence that progressively increases with advancing age. With the urgent initiation of chemotherapy, the complete remission (CR) rate of AML has been markedly improved currently.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> However, just about 70% of newly diagnosed patients with AML could achieve CR after two courses of standard induction chemotherapy.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a> Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the treatment with the highest probability of cure for AML patients. And the achievement of CR is the important milestone for patients with AML undergoing curative intent therapy. But how to improve CR rate is still the most important problem we need to conquer.</p><p id="par0010" class="elsevierStylePara elsevierViewall">According to National Comprehensive Cancer Network (NCCN) guideline, we should adopt a standard dose combination regimen or high-dose Ara-C regimen for newly diagnosed patients with AML who had no response to the primary standard chemotherapy. Another effective strategy to achieve CR was double induction which was consists of two courses of chemotherapy irrespective of the presence or absence of residual leukemic blasts in the bone marrow (BM) after the first course.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a> However, a variety of severe complications, which were important causes of high mortality for patients with AML, limited the application of double induction chemotherapy. So it is urgent to look for an approach to reduce side effects and augment tolerance of chemotherapy.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Granulocyte colony-stimulating factor (G-CSF) priming induces the mobilization of leukemic cells from their bone marrow niches into the circulation, and increases the number of leukemic blasts in the S-phase, thereby increasing their sensitivity to S-phase-active agent such as cytarabine (Ara-C).<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> Previous researches showed that priming regimen, such as CAG (Ara-C, aclarubicin and G-CSF) and HAG (homoharringtonine, Ara-C and G-CSF), increased CR rate significantly in refractory and relapsed AML patients with less side-effect and better tolerance.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5–7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Based on the above, we tried to apply G-CSF priming chemotherapy instead of the second course standard therapy to make up new double induction chemotherapy to treat AML patients who did not achieve CR after the first course, and made a comparison in the efficiency and safety between the new double induction regimen and the regimen of two courses of standard chemotherapy.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and method</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">Approval for this single-center, non-randomized, retrospective cohort study was obtained from the Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University. We performed bone marrow aspiration to access the condition of patients at days 7 after the end of the first induction course. For a part of patients who did not achieve CR, they received G-CSF combining low-dose chemotherapy as the second induction course during days 20–22 of the first one, which was named as new double induction chemotherapy. For other patients who did not achieve CR, we gave them the second standard chemotherapy two weeks later after the first one.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A total of 97 newly diagnosed AML patients who did not get CR after the first course of induction chemotherapy were included in the study. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20–22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as a control group. The efficiency and safety of new induction chemotherapy and two courses of standard chemotherapies were analyzed in this study. In subgroup analysis, we divided all patients to five groups according to FAB classification and three groups based on risk status. We also analyzed response rate of different priming regimen in priming group.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnoses of AML and risk status were based on NCCN guidelines and the category was on the basis of French–American–British (FAB) classification.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Leukocytopenia was defined as a leukocyte count less than 4.0<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L, and neutropenia was defined as an absolute neutrophil count less than 0.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L. Cardiac, hepatic and renal functions were assessed and graded on a scale of 0–4 using the National Cancer Institute (NCI) Version 2.0 criteria.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment protocols</span><p id="par0045" class="elsevierStylePara elsevierViewall">The first standard induction chemotherapy previous to salvage therapies was consisted of DA (daunorubicin 40<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–3; Ara-C 100<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–7), MA (mitoxantrone 10<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–3; Ara-C 100<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–7) and TA (perarubicin 25<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–3; Ara-C 100<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–7). The second course of standard chemotherapy in control group we used was mainly MAE (mitoxantrone 8<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–3; Ara-C 100<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–5, 7; etoposide 70<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, days 1–3).</p><p id="par0050" class="elsevierStylePara elsevierViewall">G-CSF priming regimens included HAG (homoharringtonine 1.5<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, intravenously, days 1–14; Ara-C 7.5<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, subcutaneous injection, days 1–14; G-CSF 150<span class="elsevierStyleHsp" style=""></span>μg/m<span class="elsevierStyleSup">2</span>/day, subcutaneous injection, days 0–14) and CAG (aclarubicin 12<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, intravenously, every other day; Ara-C 7.5–10<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day, subcutaneous injection, every 12<span class="elsevierStyleHsp" style=""></span>h; G-CSF 100<span class="elsevierStyleHsp" style=""></span>μg/m<span class="elsevierStyleSup">2</span>/day, subcutaneous injection, days 0–14).</p><p id="par0055" class="elsevierStylePara elsevierViewall">Symptomatic and supportive therapies were initiated based on the condition of patients. Erythrocyte suspension was administered when hemoglobin less than 7<span class="elsevierStyleHsp" style=""></span>g/dL or symptoms of anemia. Platelets (PLT) suspension was initiated when PLT counts less than 10<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L or with any signs of bleeding. Antibiotic prophylaxis was administered when absolute neutrophil count less than 0.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L and appropriate antibiotics were used according to the experience and drug sensitivity test after getting infected.</p><p id="par0060" class="elsevierStylePara elsevierViewall">When the patient achieved CR after two courses of chemotherapy, they received three to four intensification or consolidation therapies according to their age and performance status, or allo-HSCT if the proper donor was found. We continued the last regimen for the patients who got partial remission (PR) after two courses of chemotherapy. For the patients who had no response, we chose other therapy.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Response criteria and outcome analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">According to NCCN guideline, CR was defined as less than 5% bone marrow blasts with an absolute neutrophil count of more than 1.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L, a PLT count of more than 100<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L and no residual evidence of extramedullary disease. A decrease of at least 50% in the percentage of blasts to 5%–25% in the bone marrow aspiration and the normalization of blood counts as above were defined as PR. No response (NR) was defined as persistent leukemic blasts in bone marrow or peripheral blood or both, without significant decrease from pretreatment levels. Response was confirmed one to two weeks after chemotherapy. Patients who died within the first 8 weeks after start of induction treatment were considered early death (ED).</p><p id="par0070" class="elsevierStylePara elsevierViewall">Overall survival (OS) was defined as a duration from the beginning of induction chemotherapy to the date of the last follow-up or death from any cause. Disease-free survival (DFS) was considered from the date of CR to relapse, or the last follow-up or death during remission.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Adverse events assessment</span><p id="par0075" class="elsevierStylePara elsevierViewall">Routine tests for blood cell, cardiac, hepatic and renal functions were assessed pre-& post-chemotherapy. The toxicity of chemotherapy was graded on a scale of 0–4 using the National Cancer Institute (NCI) Version 2.0 criteria.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">Continuous data were compared using the independent samples <span class="elsevierStyleItalic">t</span>-test or Mann–Whitney Wilcoxon rank test. Categorical variables were compared by Pearson's chi-squared test, continuous-corrected chi-squared test or Fisher exact test. Survival rate was estimated by the Kaplan–Meier method and compared using the log-rank test. The capacity of clinical features to affect outcome was assessed by multivariate Cox regression. All tests were two-sided, and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 were defined as significant difference. All statistical analyses were performed with Statistical Product and Service Solutions (SPSS) Statistics for Windows, Version 18.0 (IBM Corp., Armonk, NY, USA).</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Characteristics of the patients</span><p id="par0085" class="elsevierStylePara elsevierViewall">A total of 97 eligible and evaluable AML patients were analyzed in this study. As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, priming group included 21 males and 24 females with a median age of 45 (10–75), while control group included 28 males and 24 females with a median age of 46 (13–67). According to FAB classification, all patients were classified to M1, M2, M4, M5 and mix cell type, and disease classification between two groups showed no difference (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.751). The two groups did not differ in risk status (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.886), chemotherapy of the first course (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.437), blood cell counts (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.351, 0.537 and 0.481, respectively, for WBC, Hb and PLT) and bone marrow blast cell percentage before the second course (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.182).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Response and outcome</span><p id="par0090" class="elsevierStylePara elsevierViewall">In patients received priming chemotherapy, the CR and RR rate (64.4% & 75.6%, respectively) were significantly higher than patients administered standard chemotherapy (28.8% & 42.3%, respectively), with <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 for CR and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001 for RR. ED had no difference between two groups (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.918) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Based on FAB classification, subgroup analysis revealed more than 50% patients achieved CR and PR in M2, M4, M5 subgroup with no significant difference (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.587). However, risk status had an influence on the CR rate (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.042) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In the priming group, the response rate (CR<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PR) had no statistically difference between HAG (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17, CR<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2 (64.7%)) and CAG (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>28, CR<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>3 (82.1%)) priming regimen subgroup (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.336).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Patients in two groups were followed up until January 15, 2017, and the median follow-up period in this study was 10.5 months (range: 2–75 months). Two patients in the priming group and one patient in the control group received HSCT and acquired long time survival. Except the patients who received HSCT, the OS rate and DFS rate were obviously higher in the priming group than in the control group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 & <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001, respectively) (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Cox regression analysis</span><p id="par0105" class="elsevierStylePara elsevierViewall">Cox regression analysis was used to detect the influence of some clinical features on outcome of patients. As shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>, WBC count before the second course (hazard ratio 1.040, 95% confidence interval 1.009–1.072) and selection of the second chemotherapy regimens (hazard ratio 0.394, 95% confidence interval 0.233–0.666) were independent prognostic factor for patients’ survival, which means mortality risk would increase approximately double when WBC increased every 10<span class="elsevierStyleSup">9</span>/L, and increase about 0.4-fold when using priming chemotherapy as a new double induction regimen. Gender, age, risk status and the percentage of bone marrow blast cells before the second course were not independent prognostic factor (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Adverse events</span><p id="par0110" class="elsevierStylePara elsevierViewall">Within the duration from the second chemotherapy to the date of the next chemotherapy beginning, adverse events were recorded. The patients in control group suffered from more permanent and severe myelosuppression than the patients in priming group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05), and the priming group had shorter time of bone marrow recovery (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). The rate of infection was distinctly lower in the priming group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.013), and no severe hemorrhage or treatment-related death was observed in the two groups. Non-hematologic toxicities, such as gastrointestinal, hepatic, renal damage, showed no difference between two groups (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05) except cardiac dysfunction (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>).</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">In this study, we combined standard chemotherapy and G-CSF priming regimen to make up new double induction chemotherapy and verified its effects by comparing two courses of standard chemotherapy in patients with newly diagnosed AML who did not achieve CR in their first course. The results showed that the patients with AML treated with standard chemotherapy followed by G-CSF priming regimen double induction had higher CR and RR rates than the AML patients treated with two courses of standard conventional regimens. The new double induction chemotherapy had a survival advantage in OS and DFS rates and slighter and transient myelosuppression or non-hematologic toxicity. In addition, WBC counts before the second course and the selection of the second chemotherapy regimen were two independent prognostic factors for AML patients. However, it should be noted that this study is a retrospective analysis with small sample size, so further prospective trials are warranted.</p><p id="par0120" class="elsevierStylePara elsevierViewall">G-CSF has served in the clinic for more than three decades to treat congenital and acquired neutropenias, in order to reduce febrile neutropenia before or during courses of intensive chemotherapy and promote the recovery of hematopoietic function.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">4,8</span></a> It is thought that G-CSF could drive G0-phase cells into S-phase,<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">9,10</span></a> promote the release of granulocytic lineage cells from the bone marrow to the peripheral blood by reducing CXCR4 expression and inhibiting osteoblast activity to decrease CXCL12 (the ligand for CXCR4) expression in the bone marrow,<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">11,12</span></a> thereby promoted chemosensitivity of leukemic cells to Ara-C. Previous studies indicated that HAG regimen was effective in remission induction for refractory and relapsed AML patients,<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5,6</span></a> hypocellular AML patients<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> and middle-and-high risk myelodysplastic syndrome (MDS).<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> The same function was also found in CAG regimen with newly diagnosed elderly AML patients<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a> and CHAG regimen in advanced MDS and high-risk AML.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a> A prospective study showed the AML patients received escalated-dose Ara-C with G-CSF priming regimen had an advantage in OS and event free survival rate when compared with the patients receiving conventional-dose Ara-C with G-CSF.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a> These results suggested that G-CSF priming chemotherapy has an advantage in improving CR rate with minimal toxicity for AML patients.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Double induction is a strategy of very early intensification by starting a second induction course on the 21st day after the first induction course,<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a> aiming to administer additional antileukemic treatment to patients who would not have attained CR with one course alone and to reduce minimal residual disease to improve the long-term outcome of patients. After the first course of chemotherapy, residual leukemic blasts were inducted to enter cell cycle simultaneously. The exact time window between day 14 and 21 after the first course of chemotherapy, the initiation of the second chemotherapy would maximally kill residual leukemic cells, and thereby improve CR rate and prolong survival of patients with AML.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a> Previous studies suggested that double induction regimen could improve CR rate and long-term survival rate of AML patients with poor prognosis.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">18,19</span></a> However, double induction might increase the treatment related mortality in older patients with AML.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a> Therefore, in the present study, we chose G-CSF priming combined with low-dose chemotherapy instead of the second standard chemotherapy to form a new double induction regimen, in order to increase the CR rate and reduce the adverse effect simultaneously.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In our study, the demographic and baseline characteristics had no statistically difference between the two groups. The patients handled by standard chemotherapy followed by G-CSF priming regimen produced a higher CR rate of 64.4% (29/45) than the patients receiving two courses of standard chemotherapy (CR rate 28.8%). Therefore, we think that new double induction regimen consisted of standard chemotherapy and G-CSF priming chemotherapy is an effective approach for AML patients to improve the CR rate. Priming regimens we used included HAG and CAG, but there was no statistically significant difference in CR rate between two priming chemotherapy. The effects of FAB classification and risk status on the response rate in all patients showed no difference, which is probably due to the small number of patients.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Intensive induction chemotherapy with standard dose and consolidation chemotherapy with middle-low dose could induce severe and permanent myelosuppression and non-hematologic damage, which increase the mortality of AML patients markedly.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">21</span></a> Ara-C plays an important role in the treatment of AML through inhibiting DNA synthesis in S-phase to disturb the proliferation of leukemic cells and its common toxicities are myelosuppression and gastrointestinal disturbance,<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">22</span></a> while rare toxicities are pericarditis, congestive heart failure,<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">23</span></a> cerebellar toxicity<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">24</span></a> and neurologic toxicity.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">22</span></a> Anthracycline, such as mitoxantrone, aclarubicin, mainly causes heart toxicity.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a> Some studies showed that lower-intensity chemotherapy should be concerned to improve their OS in AML patients who were older than 60 years or not eligible for standard chemotherapy.<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">26,27</span></a> In our study, myelosuppression and non-hematologic adverse effect of G-CSF priming regimen were slighter than conventional regimen. The possible reason was involved in low-dose chemotherapy agent we used. Thus, we hold that low-dose chemotherapy combined with G-CSF priming was lowly toxic and well tolerable.</p><p id="par0140" class="elsevierStylePara elsevierViewall">The number of WBC counts before the second course and the second chemotherapy regimen were proved to be independent factors for prognosis of AML patients in this study. The high WBC count was demonstrated to be associated with poor prognosis,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> which was in accordance with our result. Patients who were administered with priming chemotherapy have an advantage in survival. Poor-risk cytogenetics was an omen for low CR rate, which was coincided with the published study.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> Previous study also elucidated that inferior survival was related to increased age and blasts percentage,<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> but this relationship has not been reflected in our study. Small sample may be the reason for this.</p><p id="par0145" class="elsevierStylePara elsevierViewall">In summary, new double induction regimen composed by standard chemotherapy and G-CSF priming combined with low-dose chemotherapy in patients with newly diagnosed AML who did not receive CR in the first course gives promising results. When compared with two courses of standard chemotherapy, we believe it represents a feasible and effective therapeutic strategy and offers the potential to avoid unnecessary toxicity in newly diagnosed patients with AML.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1097516" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1039122" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1097517" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1039121" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and method" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Treatment protocols" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Response criteria and outcome analysis" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Adverse events assessment" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Characteristics of the patients" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Response and outcome" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Cox regression analysis" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Adverse events" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "xack372822" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-03-09" "fechaAceptado" => "2017-11-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1039122" "palabras" => array:4 [ 0 => "Double induction chemotherapy" 1 => "Granulocyte colony-stimulating factor priming" 2 => "Acute myeloid leukemia" 3 => "Complete remission" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1039121" "palabras" => array:4 [ 0 => "Quimioterapia de doble inducción" 1 => "Cebado de factor estimulante de colonias de granulocitos" 2 => "Leucemia mieloide aguda" 3 => "Remisión completa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20–22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Between the two groups there were no differences in the French–American–British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Discussion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Para mejorar la tasa de respuesta completa (RC) en los pacientes con diagnóstico reciente de leucemia mieloide aguda (LMA), y aliviar los efectos secundarios graves de la quimioterapia de doble inducción, combinamos un régimen estándar de quimioterapia de cebado de factor estimulante de colonias de granulocitos (G-CSF) para componer un nuevo régimen de doble inducción para los pacientes de LMA que no pudieron lograr la RC tras la administración del primer curso.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se incluyó a 95 pacientes de LMA que no lograron la RC tras el primer curso de quimioterapia estándar. Entre ellos, a 45 pacientes se les administró cebado de G-CSF junto con baja dosis de quimioterapia durante los días 20 a 22 del primer curso, formando el grupo de cebado, y a 52 pacientes se les administró quimioterapia estándar de nuevo, y constituyeron el grupo control.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">No se produjeron diferencias entre los 2 grupos conforme a la clasificación French-American-British (FAB), estatus del riesgo, primer curso de quimioterapia, recuento de hematocritos o porcentaje de blastos de la médula ósea con anterioridad al inicio del segundo curso. Pero la tasa de RC fue significativamente superior, y los efectos adversos fueron inferiores, en el grupo de cebado con respecto al grupo control. El análisis de regresión multivariante de Cox reflejó que el nivel leucocitario antes del segundo curso, y la selección del segundo régimen de quimioterapia fueron 2 factores independientes de la supervivencia larga de los pacientes.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estos resultados esclarecen que la quimioterapia estándar seguida de quimioterapia de inducción doble de cebado de G-CSF constituye un método efectivo para mejorar la tasa de RC y reducir los efectos adversos en los pacientes de LMA.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Discusión" ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1331 "Ancho" => 1530 "Tamanyo" => 70066 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Overall survival rate of two groups.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1284 "Ancho" => 1570 "Tamanyo" => 68342 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Disease-free survival rate of two groups.</p>" ] ] 2 => 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:3 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">FAB, French–American–British; WBC, white blood cell; Hb, hemoglobin; PLT, platelet.</p>" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Priming group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Number</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Gender, no (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.481 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (46.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 (53.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (53.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age, median (range)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 (10–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46 (13–67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.617 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FAB classification, no (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.751 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (3.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (20.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (46.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (31.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (23.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mix cell type \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Risk status</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>, <span class="elsevierStyleItalic">no (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.886 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 (37.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (42.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Intermediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 (40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 (38.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (22.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (19.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">First course therapy, no (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.437 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>MA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 (55.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>TA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 (40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27 (51.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Blood cell counts before the second course</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>WBC (×10<span class="elsevierStyleSup">9</span>/L), median (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.90 (0.99–44.36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.70 (1.48–52.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.351 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hb (g/dL), median (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.4 (5.4–10.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.5 (5.9–10.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.537 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PLT (×10<span class="elsevierStyleSup">9</span>/L), median (range) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (3–145) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32.5 (5–309) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.481 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Bone marrow blast cell percentage before the second course</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44 (7–84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 (8–85.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.182 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1875871.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Risk status of AML was established according NCCN guidelines.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Demographic and baseline characteristics.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CR, complete remission; PR, partial remission; RR, complete and partial remission; ED, early death.</p>" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Response \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Priming group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CR, no. (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 (64.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (28.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PR, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (13.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.726 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RR, no. (%)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 (75.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 (42.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ED, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.918 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1875872.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">P<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Response of two types of chemotherapy.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">CR, complete remission; PR, partial remission.</p>" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristic \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CR<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PR (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">FAB classification</span></td><td class="td" title="table-entry " align="char" valign="top">0.587 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>0 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1 (59.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>5 (55.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>6 (65.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mix cell type \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Risk status</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">*</span></a></td><td class="td" title="table-entry " align="char" valign="top">0.042 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>4 (69.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Intermediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>6 (57.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Poor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2 (35.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1875869.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">P<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Effects of FAB classification and risk status on the response rate in all patients.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">HR, hazard ratio; CI, confidence interval; WBC, white blood cell.</p>" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Risk factors \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.188 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.923 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">[0.543, 1.568] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.846 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">[0.992, 1.022] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC count<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.040 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">[1.009, 1.072] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk status \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.104 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.340 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">[0.941, 1.907] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chemotherapy regimen<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.394 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">[0.233, 0.666] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone marrow blast cell percentage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.177 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">[0.996, 1.020] \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1875873.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">P<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Prognostic factors for survival identified by Cox regression analysis.</p>" ] ] 6 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Priming group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Leucopenia, no. (%)<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 (82.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.005 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutropenia, no. (%)<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (57.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 (96.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Time to reach >0.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L (days)<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (0–16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.5 (0–30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anemia, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thrombocytopenia, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 (93.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49 (94.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Time to reach >20<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L (days)<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (0–16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (0–35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nausea, vomiting, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (9.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.094 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liver dysfunction, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (13.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (17.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.589 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kidney dysfunction, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cardiac dysfunction, no. (%)<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (17.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.036 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oral ulcer, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neutropenic fever, no. (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (48.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (67.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.066 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infection, no. (%)<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 (42.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (76.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.013 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1875870.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">P<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Adverse events during induction (NCI grade 3&4).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How I treat acute myeloid leukemia presenting with preexisting comorbidities" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Y. 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Original article
Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia
La adición de factor estimulante de colonias de granulocitos a la quimioterapia de rescate es más efectiva que la quimioterapia de rescate en el tratamiento de la recidiva de la leucemia mieloide aguda