Association of an expanded inflammatory mediators response with clinical and laboratory data in the postoperative period of pulmonary resection: a prospective clinical study / Associação de perfil ampliado dos mediadores da resposta inflamatória com dados clínicos e laboratoriais no período pós-operatório de ressecção pulmonar: estudo clínico prospectivo

ABSTRACT Introduction: patients undergoing pulmonary resection may experience local or remote complications in the postoperative period due to the inflammatory response, which increases the length of hospital stay and costs. This study objective was to establish an expanded interleukins profile, identifying the main actors in the postoperative inflammatory response, and to correlate them with clinical and laboratory data of patients submitted to pulmonary resection. Methods: this was a prospective, interventional, longitudinal study of 27 cases of pulmonary resection performed at HC-UNICAMP, in which we analyzed serum levels of IL 1 α, IL 1 β, IL 1 ra, IL 2, IL 13, IL 6, IL 8, IL 10, IL 12 (p40), IL 12 (p70), IL 17a, TNF α, TNF β, IFN γ, TGF β, MIP 1α, MIP 1β, MCP 1, MCP 3, VEGF, and clinical data before, during, and after surgery. Results: Individuals had a median age of 63 years, 16 (59%) being male and 11 (41%), female. The clinical factors that influenced inflammatory response were body mass index, smoking, and previous use of corticosteroids, while the influencing laboratory data were the numbers of leukocytes and platelets. Discussion: within this expanded interleukin profile in the inflammatory response of lung resections, our study showed that interleukins IL 6, IL 8, IL 10, IL 1 β, and TNF α should be considered for assessing humoral inflammation. Conclusion: this study can aid in the identification of clinical or pharmacological interventions that modulate the inflammatory response in the perioperative period of pulmonary resections, mitigating local and systemic complications.

RESUMO Introdução: pacientes submetidos a ressecção pulmonar podem apresentar complicações locais ou remotas no pós-operatório decorrente da resposta inflamatória, que aumenta o tempo de internação e de custos hospitalares. O objetivo deste trabalho foi estabelecer perfil ampliado do comportamento das interleucinas, identificar as principais interleucinas que atuam na resposta inflamatória no período pós-operatório e associá-las com dados clínicos e laboratoriais dos pacientes submetidos a ressecção pulmonar. Métodos: Estudo prospectivo com 27 casos de ressecção pulmonar realizados no HC-UNICAMP. Foram analisados níveis séricos de IL-1 α, IL-1 β, IL-1 ra, IL-2, IL-13, IL-6, IL-8, IL-10, IL-12 (p40), IL-12 (p70), IL-17a, TNF- α, TNF- β, IFN-γ, TGF- β, MIP-1 α, MIP-1 β, MCP-1, MCP-3, VEGF e dados clínicos antes, durante e após a operação. Resultados: indivíduos apresentaram mediana de idade de 63 anos, sendo 16 (59%) do sexo masculino e 11 (41%) do sexo feminino. Os fatores clínicos que influenciam na resposta inflamatória são: índice de massa corporal, tabagismo e uso prévio de corticóide, enquanto que os dados laboratoriais se expressam nos números de leucócitos e plaquetas. Discussão: dentro deste ampliado perfil das interleucinas na resposta inflamatória das ressecções pulmonares, este estudo mostrou que devem ser valorizadas para avaliar inflamação humoral as interleucinas: IL-6, IL-8, IL-10, IL-1 β e TNF- α. Conclusão: este estudo pode colaborar na identificação de intervenções clínicas ou farmacológicas que modulem a resposta inflamatória no período peri-operatório das ressecções pulmonares, mitigando as complicações locais e sistêmicas.

Relationship between anxiety, depression and quality of life with the intensity of reflex sweating after thoracoscopic sympathectomy for treatment of primary hyperhidrosis / Relação entre ansiedade, depressão e qualidade de vida com a intensidade da sudorese reflexa após simpatectomia torácica por videocirurgia para tratamento da hiperidrose primária

ABSTRACT Objective: to compare the intensity of reflex sweating with the degree of anxiety and its interference in the quality of life of patients undergoing Thoracoscopic (VATS) sympathectomy in the pre- and postoperative period. Methods: we evaluated 54 patients with a mean age of 26 years (16-49 years) undergoing sympathectomy in the R3-R4 level. We applied two questionnaires at three different times: "Quality of life in patients with primary hyperhidrosis" and "Scale for anxiety and depression". Results: of the patients studied, 93% showed significant improvement in quality of life 30 days after surgery, the effects remaining after six months. There were no postoperative complications. The patient's level of anxiety is highly correlated with the intensity of reflex sweating after 30 and 180 days. Conclusion: Thoracoscopic sympathectomy improves quality of life of patients with primary hyperhidrosis, even with the emergence of reflex sweating. Anxiety directly relates to the intensity of reflex sweating, without compromising the degree of patient satisfaction.

RESUMO Objetivo: avaliar a intensidade de sudorese reflexa com o grau de ansiedade e sua interferência na qualidade de vida de indivíduos submetidos à simpatectomia por videotoracoscopia nos períodos pré e pós-operatório. Métodos: foram avaliados 54 pacientes com média de idade de 26 anos (16 a 49 anos), submetidos à simpatectomia em nível R3-R4. Dois questionários foram aplicados em três momentos diferentes: "Qualidade de vida em pacientes com hiperidrose primária e "Escala para ansiedade e depressão". Resultados: dos pacientes estudados, 93% mostrou melhora significativa na qualidade de vida após 30 dias da cirurgia, com os efeitos remanescentes após seis meses. Não houve complicações pós-operatórias. A análise mostrou que o nível de ansiedade do paciente é altamente correlacionado com a intensidade da sudorese reflexa após 30 e 180 dias. Conclusão: a simpatectomia torácica por videotoracoscopia melhora a qualidade de vida de pacientes com hiperidrose primária, mesmo com o surgimento de sudorese reflexa. A ansiedade está diretamente relacionada com a intensidade da sudorese reflexa, sem comprometer o grau de satisfação do paciente.

Age-adjusted international prognostic index is a predictor of survival in gastric diffuse B-cell non-Hodgkin lymphoma patients

Background The clinical course of gastric lymphoma is heterogeneous and clinical symptoms and some factors have been related to prognosis. Objective The present study aims to identify prognostic factors in gastric diffuse B-cell non-Hodgkin lymphoma diagnosed and treated in different countries. Methods A consecutive series of gastric diffuse B-cell non-Hodgkin lymphoma patients diagnosed and treated in Brazil, Portugal and Italy, between February 2008 and December 2014 was evaluated. Results Of 104 patients, 57 were female and the median age was 69 years (range: 28­88). The distribution of the age-adjusted international prognostic index was 12/95 (13%) high risk, 20/95 (21%) high-intermediate risk and 63/95 (66%) low/low-intermediate risk. Symptoms included abdominal pain (63/74), weight loss (57/73), dysphagia (37/72) and nausea/vomiting (37/72). Bulky disease was found in 24% of the cases, anemia in 33 of 76 patients and bleeding in 22 of 72 patients. The median follow-up time was 25 months (range: 1­77 months), with 1- and 5-year survival rates of 79% and 76%, respectively. The multivariate Cox Regression identified the age-adjusted international prognostic index as a predictor of death (hazard risk: 3.62; 95% confidence interval: 2.21­5.93; p-value <0.0001). Conclusions This series identified the age-adjusted international prognostic index as predictive of mortality in patients treated with conventional immunochemotherapy.

Mobilization and collection of CD34+ cells for autologous transplantation of peripheral blood hematopoietic progenitor cells in children: analysis of two different granulocyte-colony stimulating factor doses

The use of peripheral hematopoietic progenitor cells (HPCs) is the cell choice in autologous transplantation. The classic dose of granulocyte-colony stimulating factor (G- CSF) for mobilization is a single daily dose of 10 µg/kg of patient body weight. There is a theory that higher doses of granulocyte-colony stimulating factor applied twice daily could increase the number of CD34+ cells collected in fewer leukapheresis procedures. Objective: The aim of this study was to compare a fractionated dose of 15 µg G-CSF/kg of body weight and the conventional dose of granulocyte-colony stimulating factor in respect to the number of leukapheresis procedures required to achieve a minimum collection of 3 × 106 CD34+ cells/kg body weight. Methods: Patients were divided into two groups: Group 10 - patients who received a single daily dose of 10 µg G-CSF/kg body weight and Group 15 - patients who received a fractioned dose of 15 µg G-CSF/kg body weight daily. The leukapheresis procedure was carried out in an automated cell separator. The autologous transplantation was carried out when a minimum number of 3 × 106 CD34+ cells/kg body weight was achieved. Results: Group 10 comprised 39 patients and Group 15 comprised 26 patients. A total of 146 apheresis procedures were performed: 110 (75.3%) for Group 10 and 36 (24.7%) for Group 15. For Group 10, a median of three (range: 1-7) leukapheresis procedures and a mean of 8.89 × 106 CD34+ cells/kg body weight (±9.59) were collected whereas for Group 15 the corresponding values were one (range: 1-3) and 5.29 × 106 cells/kg body weight (±4.95). A statistically significant difference was found in relation to the number of apheresis procedures (p-value <0.0001). Conclusions: To collect a minimum target of 3 × 106 CD34+ cells/kg body weight, the administration of a fractionated dose of 15 µg G-CSF/kg body weight significantly decreased the number of leukapheresis procedures performed.

Outcomes of autologous transplantation for multiple myeloma according to different induction regimens

Background: Induction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma. Objective: The aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone. Methods: The records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis. Results: This study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study).The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1%) and in the thalidomide and dexamethasone group (59.2%) than in the vincristine, doxorubicin, and dexamethasone group (16.2%). The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%. Conclusion: Although the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line ...

Descriptive analysis of and overall survival after surgical treatment of lung metastases / Analise descritiva e sobrevida global do tratamento cirurgico das metastases pulmonares

OBJECTIVE: To describe demographic characteristics, surgical results, postoperative complications, and overall survival rates in surgically treated patients with lung metastases. METHODS: This was a retrospective analysis of 119 patients who underwent a total of 154 lung metastasis resections between 1997 and 2011. RESULTS: Among the 119 patients, 68 (57.1%) were male and 108 (90.8%) were White. The median age was 52 years (range, 15-75 years). In this sample, 63 patients (52.9%) presented with comorbidities, the most common being systemic arterial hypertension (69.8%) and diabetes (19.0%). Primary colorectal tumors (47.9%) and musculoskeletal tumors (21.8%) were the main sites of origin of the metastases. Approximately 24% of the patients underwent more than one resection of the lesions, and 71% had adjuvant treatment prior to metastasectomy. The rate of lung metastasis recurrence was 19.3%, and the median disease-free interval was 23 months. The main surgical access used was thoracotomy (78%), and the most common approach was wedge resection with segmentectomy (51%). The rate of postoperative complications was 22%, and perioperative mortality was 1.9%. The overall survival rates at 12, 36, 60, and 120 months were 96%, 77%, 56%, and 39%, respectively. A Cox analysis confirmed that complications within the first 30 postoperative days were associated with poor prognosis (hazard ratio = 1.81; 95% CI: 1.09-3.06; p = 0.02). CONCLUSIONS: Surgical treatment of lung metastases is safe and effective, with good overall survival, especially in patients with fewer metastases. .

OBJETIVO: Descrever características demográficas, resultados operatórios, complicações pós-operatórias e taxa de sobrevida global em pacientes com metástases pulmonares tratados cirurgicamente. MÉTODOS: Análise retrospectiva de 119 pacientes submetidos a um total de 154 cirurgias de ressecção de metástase pulmonar entre 1997 e 2011. RESULTADOS: Do total de 119 pacientes, 68 (57,1%) eram do sexo masculino, e 108 (90,8%) eram brancos. A mediana de idade foi de 52 anos (variação, 15-75 anos). Nessa amostra, 63 pacientes (52,9%) apresentaram comorbidades, sendo as mais frequentes hipertensão arterial sistêmica (69,8%) e diabetes (19,0%). Tumores primários colorretais (47,9%) e musculoesqueléticos (21,8%) foram os principais sítios de origem das metástases. Aproximadamente 24% dos pacientes foram submetidos a mais de uma ressecção das lesões, e 71% fizeram tratamento adjuvante prévio à metastasectomia. A taxa de recidiva de metástase pulmonar foi de 19,3%. A mediana do intervalo livre de doença foi de 23 meses. A principal via de acesso usada foi toracotomia (78%), e o tipo de ressecção mais frequente foi em cunha e segmentectomia (51%). O índice de complicações pós-operatórias foi de 22% e o de mortalidade perioperatória foi de 1,9%. As taxas de sobrevida global em 12, 36, 60 e 120 meses foram, respectivamente, de 96%, 77%, 56% e 39%. A análise de Cox confirmou que complicações nos primeiros 30 dias pós-operatórios associaram-se a pior prognóstico (hazard ratio = 1,81; IC95%: 1,09-3,06; p = 0,02). CONCLUSÕES: O tratamento cirúrgico das metástases pulmonares oriundas de diferentes sítios tumorais é efetivo e seguro, com boa sobrevida global, especialmente nos casos com um menor número de lesões ...

Functional evaluation indicates physical losses after hematopoietic stem cell transplantation

OBJECTIVE: To perform a function evaluation of patients before and after hematopoietic stem cell transplantation. METHODS: From November 2008 to November 2010, 29 female (58%) and 21 male patients (42%) with median age of 48 years (range: 24-67) were enrolled in this study. Data collection was performed before and after autologous or allogeneic hematopoietic stem cell transplantation. Evaluation instruments included the 2-minute walking test to evaluate gait performance with assessment of the oxygen saturation, heart rate and Borg Scale before and after the test; grip strength for strength evaluation, Schober Test for spine mobility testing and maximum and adapted activity scores of the Human Activity Profile questionnaire to test functionality in daily activities. RESULTS: Fifty patients were evaluated at baseline; six did not undergo hematopoietic stem cell transplantation (three died, one refused and two were excluded). Thus 44/50 (88% - 21 allogeneic and 23 autologous) transplantations were performed. Only 33 of the 44 patients (75%) performed evaluations after transplantation (nine died and two were excluded). Of the patients who performed both evaluations, significantly lower values were found in the evaluation after transplantation for the 2-minute walking test (p-value = 0.004), grip strength of both right and left hands (p-value = 0.004 and p-value < 0.0001, respectively), the Schober Test, and maximum and adapted activity scores (p-value < 0.0001). The heart rate was higher (p-value = 0.01) before the 2-minute walking test and oxygen saturation was higher (p-value = 0.02) after. CONCLUSION: Statistical differences indicate functional impairment after transplantation showing physical losses in this population.

Evaluation of respiratory conditions in early phase of hematopoietic stem cell transplantation

OBJECTIVE: To investigate the effectiveness of respiratory physiotherapy based on clinical evidence and analyze the improvement in respiratory parameters. METHODS: A prospective study was carried out in the Bone Marrow Transplant Unit of the Universidade Estadual de Campinas (UNICAMP). Two different previously established respiratory physiotherapy protocols were applied from days D-1 to D+7 that aimed to improve airway clearance, pulmonary re-expansion and the strengthening of respiratory muscles. Group A were subjected to diaphragmatic proprioceptive stimulation, breathing exercises, incentive spirometry with Respiron®, inspiratory muscle training with the Threshold® Inspiratory Muscle Training device, bronchial hygienization with Shaker® and cough stimulation. Group B performed a protocol that only used incentive spirometry. The parameters analyzed were: tidal volume, minute volume, maximal inspiratory pressure, maximal expiratory pressure, oxygen saturation, heart rate and respiratory frequency. RESULTS: Sixty-seven patients submitted to myeloablative hematopoietic stem cell transplantation were included in this study. Among these, thirty-nine were evaluated and randomized in the two groups. There were significant differences between the groups for tidal volume at D+2 (p-value = 0.007) and maximal inspiratory pressure (p-value = 0.03), maximal expiratory pressure (p-value = 0.03) and tidal volume (p-value = 0.004) at D+7. CONCLUSION: On comparing Group A with Group B, the authors concluded that the protocol of respiratory physiotherapy applied in this study resulted in an improvement in ventilation and in respiratory muscle strength of patients submitted to hematopoietic stem cell transplantation.

Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas

OBJECTIVE: To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. METHODS: High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma) submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m²) and granulocyte-colony stimulating factor (300 µg/day), followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m²) and methotrexate (8 g/m² only for Hodgkin's lymphoma) and autologous hematopoietic stem cell transplantation. RESULTS: At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65) years old, 78 percent had diffuse large B-cell lymphoma and 83 percent had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68) years old, 64.9 percent had the nodular sclerosis subtype and 65 percent had stage III/IV disease. Nine Hodgkin's lymphoma patients (13 percent) and 10 (9 percent) non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29 percent, 59 percent and 26 percent, respectively. In non-Hodgkin lymphoma, these values were 40 percent, 49 percent and 31 percent, respectively. High-dose cyclophosphamide-related mortality was 10 percent for Hodgkin's lymphoma and 5 percent for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. CONCLUSIONS: Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. ...

A multicenter feasibility study of chronic graft-versus-host disease according to the National Institute of Health criteria: efforts to establish a Brazil-Seattle consortium as a platform for future collaboration in clinical trials

BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76 percent) met the criteria of overlap syndrome and eight (24 percent) the classic subcategory. The overall severity of disease was moderate in 21 (62 percent) and severe in 13 (38 percent) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75 percent. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.

Associação entre HLA e leucemia em uma população brasileira de etnia mista / Association between HLA and leukemia in a mixed Brazilian population

OBJETIVOS: O objetivo deste estudo foi investigar a freqüência de antígenos HLA Classe I e de alelos HLA Classe II em 164 pacientes com vários tipos de leucemias: 35 pacientes com LLA (leucemia linfóide aguda), 50 com LMA (leucemia mielóide aguda) e 78 com LMC (leucemia mielóide crônica). MÉTODOS: A tipagem HLA Classe I foi realizada por microlinfocitotoxicidade e a de Classe II por PCR-SSP (polymerase chain reaction - sequence specific of primers), ambas da One Lambda (Canoga Park, CA, US). RESULTADOS: Em pacientes com LLA, as freqüências das variantes HLA-B45 e HLA-B56 foram maiores (P = 0,02; OR = 3,13; 95 por centoIC = 0,94-10,44; P = 0,03; OR = 3,61; 95 por centoIC = 0,47-27,64, respectivamente), quando comparadas com controles. Nos pacientes com LMA, a freqüência de HLA-B7 (P = 0,01; OR = 2,41; 95 por centoIC = 1,25-4,67) foi maior que em controles. A presença de HLA-B45 (P= 0,01; OR = 3,29; 95 por centoIC = 1,46-7,40) e de HLA-DRB1*04 (P = 0,002; OR = 2,17; 95 por centoIC = 1,36-3,46) e HLA-DRB1*08 (P = 0,004; OR = 2,36; 95 por centoIC = 1,34-4,16) foi associada ao maior risco de desenvolver LMC. CONCLUSÃO: Nossos resultados sugerem que variantes HLA conferem susceptibilidade a algumas formas de leucemia e podem prover novas ferramentas para a investigação da genética e etiologia desta doença.

OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia), 50 with AML (acute myeloid leukemia) and 78 with CML (chronic myeloid leukemia). METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers) (One Lambda, Canoga Park, CA, USA). RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95 percentIC = 0.94-10.44; P = 0.03; OR = 3.61; 95 percentIC = 0.47-27.64, respectively), than in controls. In patients with AML, the frequency of HLA-B7 (P = 0.01; OR = 2.41; 95 percentIC = 1.25-4.67) was higher than in controls. The presence of HLA-B45 (P= 0.01; OR = 3.29; 95 percentIC = 1.46-7.40), HLA-DRB1*04 (P = 0.002; OR = 2.17; 95 percentIC = 1.36-3.46) and HLA-DRB1*08 (P = 0.004; OR = 2.36; 95 percentIC = 1.34-4.16) was associated to increased risk of CML developing. CONCLUSION: Our results suggest that variants of HLA confer susceptibility to the same forms of leukemia, and could provide new tools for the investigation of genetics and etiology of this disease.

Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience

CONTEXT: Young patients affected by acute myeloid leukemia (AML) achieve complete remission (CR) using conventional chemotherapy in about 55-85 percent. However, 30 percent of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML) in younger adult patients (age < 60 years). DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil...