Ricardo Bigni - Academia.edu (original) (raw)

Papers by Ricardo Bigni

Hematology, Transfusion and Cell Therapy, 2020

International Journal of Gynecology & Obstetrics, 2009

Primary colorectal diffuse large B-cell lymphoma (DLBCL) is very rare colon malignancy. Due to a ... more Primary colorectal diffuse large B-cell lymphoma (DLBCL) is very rare colon malignancy. Due to a possible delay in the diagnosis, it is important to know the main demographic and clinical characteristics of these patients. Retrospective analysis of 18 patients diagnosed with primary colorectal DLBCL during a 17-year period at the tertiary National Cancer Institute of Brazil (INCA) hospital. Demographic characteristics, tumor localization, HIV status, lactate dehydrogenase (LDH) levels, treatment modality and follow-up status were obtained from medical records. Survival was estimated from the date of diagnosis until death. There were 11 male and seven female patients in our cohort, the median age at diagnosis was 59.5 years and four patients were HIV positive. Tumor was mainly localized in the right proximal colon. Patients were treated with chemotherapy (CT) and/or surgical resection. Eleven patients died during a median follow-up of 59 months and the median survival time was 10 months for the whole group. Six or more cycles of CT (HR = 0.19; CI 95% 0.054-0.660, p = 0.009), low LDH levels (HR = 0.229; CI 95% 0.060-0.876, p = 0.031) and surgical resection (HR = 0.23; CI 95% 0.065-0.828, p = 0.030) were associated with reduced risk of death in univariate analysis. DLBCL affected more frequently middle-aged man and was primarily located in the right colon. These observations should be considered for differential diagnosis. Six cycles of CT, low LDH levels and surgical resection were associated with better survival. Our results are consistent with previous publications and address the importance of correct colorectal DLBCL diagnosis and treatment.

Pre-engraftment cytomegalovirus infection (CMVi) is a challenge in patients receiving allogeneic ... more Pre-engraftment cytomegalovirus infection (CMVi) is a challenge in patients receiving allogeneic stem cell transplantation (Allo-HCT), as few data have been reported on its clinical importance. This study describes the clinical outcomes of pre-engraftment CMVi and compares them with those of episodes developing after engraftment in HCT patients. We performed a retrospective study of patients who underwent Allo-HCT from 2016 to 2020, including 111 recipients monitored by real-time PCR assay. Clinically significant CMVi (csCMVi) was documented in 81 (73%) patients. There were 29 (26%) cases of pre-engraftment csCMVi. No significant difference was observed regarding virological features, but patients with pre-engraftment csCMVi had a delayed start in treatment (24 vs. 12 days, p

Blood, Dec 7, 2017

Introduction:Adult T-cell leukemia/lymphoma (ATLL) is a disease that develops in a small proporti... more Introduction:Adult T-cell leukemia/lymphoma (ATLL) is a disease that develops in a small proportion of individuals who are chronically infected with human T-cell lymphotropic virus type 1 (HTLV-1). Infection is endemic in some parts of the world, Brazil included1. According to the Shimoyama classification, there are four ATLL subtypes: (1) acute, (2) lymphomatous, (3) chronic, and (4) smoldering2. The acute and lymphomatous subtypes are grouped together as aggressive subtypes and often appear with hypercalcemia, cutaneous lesions and visceral dysfunctions. To define a first line treatment for aggressive ATLL is challenging, as the disease is often refractory even to intensive chemotherapy. According to a meta-analysis, patients with the acute subtype should receive antiviral therapy with zidovudine (AZT) and interferon-alfa (INF) and patients with the lymphomatous subtype should receive chemotherapy, both followed by allogeneic stem cell transplantation (ASCT) when feasible3. The aim of this study is to describe the clinical and laboratory characteristics, as well as outcomes of patients with aggressive ATLL treated at a single center in Rio de Janeiro, Brazil. Methods: This is a retrospective study. All patients diagnosed with acute or lymphomatous ATLL (according to the Shymoiama classification) between January 2011 and January 2017 have been evaluated. Diagnosis criteria included positive serology for HTLV-1 and histologically or cytologically proven T-cell malignancy. All patients were treated and followed-up in the Hematology Department of Instituto Nacional de Cancer in Rio de Janeiro, Brazil. Statistical analyses were performed using SPSS software, version 21 (SPPS Inc., Chicago, IL, USA). Results: A total of 28 patients with aggressive ATLL were analyzed: patient characteristics are summarized in Table 1. Most patients (57%) were treated initially with chemotherapy (CT), usually CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) with 21-days intervals between cycles. Remaining patients were treated with antiviral therapy (AZT/INF). Treatment was considered adequate for the clinical subtype in 23 patients (82%). All patients received monthly intratechal chemotherapy. Complete response was achieved in 5 patients (18%) and partial response in 3 additional patients (11%), with an overall response rate of only 29%. Median survival time was 16.7 months (8 and 17 months for acute and lymphoma types, respectively, not statistically significant). The only factor associated with better survival was at least partial response to first line treatment (Fig 1). The main cause of death was progression of the primary disease. Only three patients (10%) were submitted to ASCT (two related and one unrelated). Two are alive one year after transplantation without evidence of the disease. The other patient died a few months after the transplantation of progressive disease. Discussion: Treatment of aggressive ATLL is challenging, as patients often appear with a heavy tumor burden and a disease refractory to primary treatment or quickly relapse after remission. A large recent Japanese study including 344 patients with aggressive ATLL showed survival times of 8.3 and 10.6 months for the acute and lymphomatous subtypes, respectivelly4. Despite the limitations of our study, including its retrospective nature and the small sample, our resultsprovide relevant information from cases of an endemic area with limited number of studies. At least a partial response to first line treatment is necessary for long term survival. Conclusion:Treatment of aggressive ATLL are ineffective and limited. The challenge is to develop therapeutic approaches with higher response rates and to increase the number of patients undergoing ASCT. References 1 - Proietti FA, Carneiro-Proietti ABF, Catalan-Soares BC, et al. Global epidemiology of HTLV-1 infection and associated diseases. Oncogene 2005;24:6058-68 2 - Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukemia-lymphoma. Br J Haematol 1991;79:428-37 3 - Bazerbachi A, Plumelle Y, Ramos JC, et al. Meta-analysis on the use of zidovudine and interferon-alpha in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol 2010;28:4177-83 4 - Katsuya H, Ishitsuka K, Utsunomiya A, et al. Treatment and survival among 1594 patients with ATL. Blood 2015;126:2570-2577. Disclosures No relevant conflicts of interest to declare.

International Journal of Stem Cells, 2021

The osteogenic differentiation potential of mesenchymal stromal cells (hMSCs) is an essential pro... more The osteogenic differentiation potential of mesenchymal stromal cells (hMSCs) is an essential process for the haematopoiesis and the maintenance of haematopoietic stem cells (HSCs). Therefore, the aim of this work was to evaluate this potential in hMSCs from AML patients (hMSCs-AML) and whether it is associated with BMP4 expression. The results showed that bone formation potential in vivo was reduced in hMSCs-AML compared to hMSCs from healthy donors (hMSCs-HD). Moreover, the fact that hMSCs-AML were not able to develop supportive haematopoietic cells or to differentiate into osteocytes suggests possible changes in the bone marrow microenvironment. Furthermore, the expression of BMP4 was decreased, indicating a lack of gene expression committed to the osteogenic lineage. Overall, these alterations could be associated with changes in the maintenance of HSCs, the leukaemic transformation process and the development of AML.

Oral Diseases, 2021

OBJECTIVES Lymphomas represent around 10% of head and neck neoplasms, among which the diffuse lar... more OBJECTIVES Lymphomas represent around 10% of head and neck neoplasms, among which the diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype. In the present study, we characterized demographic parameters, anatomical sites and survival rates of patients in a Brazilian cancer center. MATERIALS AND METHODS Single-center retrospective epidemiological study of 243 head and neck DLBCL patients. Demographic characteristics, tumor localization, HIV status, lactate dehydrogenase (LDH) activity and treatment modality were obtained from electronic medical records. RESULTS The most common primary head and neck tumor location in patients with DLBCL was Waldeyer's ring. Interestingly, age above 80 years, male gender, high LDH levels and HIV positivity were significantly associated with shorter overall survival (OS) rates and increased risk of death. We further demonstrated that treatment had a protective effect, improving OS and reducing risk of death. Notably, we found no benefit of combination of chemotherapy and radiotherapy versus isolated treatment modalities. CONCLUSION The study showed that primary head and neck DLBCL is more incident in middle age and elderly patients with a small male patients' majority in a Brazilian population. Moreover, we observed a 3-year OS rate of almost 60% and multivariate analysis showed that treatment was the only protective factor.

Hematology, Transfusion and Cell Therapy, 2020

During the COVID-19 pandemic, special attention has been addressed in cancer care to mitigate the... more During the COVID-19 pandemic, special attention has been addressed in cancer care to mitigate the impact on the patient's prognosis. We addressed our preparation to face COVID-19 pandemic in a Hematological and Stem Cell Transplant Unit in Brazil during the first two months of COVID-19 pandemic and described COVID-19 cases in patients and health care workers (HCW). Modifications in daily routines included a separation of area and professionals, SARS-CoV-2 screening protocols, and others. A total of 47 patients and 54 HCW were tested for COVID-19, by PCR-SARS-CoV-2. We report 11 cases of COVID-19 in hematological patients (including 2 post stem cell transplant) and 28 cases in HCW. Hematological cases were most severe or moderate and presented with several poor risk factors. Among HCW, COVID-19 were mostly mild, and all recovered without hospitalization. A cluster was observed among HCW. Despite a decrease in the number of procedures, the Transplant Program performed 8 autologous and 4 allogeneic SCT during the period, and 49 onco-hematological patients were admitted to continuing their treatments. Although we observed a high frequency of COVID-19 among patients and HCW, showing that SARS-CoV-2 is disseminated in Brazil, hematological patients were safely treated during pandemic times.

Bone Marrow Transplantation, 2021

TO THE EDITOR: Cytomegalovirus (CMV) infection leads to high morbidity in patients undergoing all... more TO THE EDITOR: Cytomegalovirus (CMV) infection leads to high morbidity in patients undergoing allogeneic stem cell transplantation (alloHCT) [1, 2]. Monitoring CMV DNAemia, preemptive antiviral therapies (PET) to prevent tissue-invasive disease and recently letermovir prophylaxis are the standard of care for these patients [3–5]. Letermovir prophylaxis is recommended to start with the first 30 days after transplantation, but some patients develop a very early CMV DNAemia, sometimes before engraftment [1, 2]. Recently, Solano et al. published a large multicenter study addressing pre-engraftment CMV DNAemia [6]. They showed that patients who developed pre-engraftment CMV DNAemia had more episodes of CMV recurrences than those with post-CMV DNAemia, but no impact in overall survival was found [6]. In their study, time to engraftment was not addressed as an outcome. Ganciclovir has significant adverse effects, including myelotoxicity, and CMV itself is a well-known myelotoxic pathogen [3, 5]. This study addressed the impact on engraftment time in HCT patients who developed pre-engraftment CMV DNAemia. In an observational retrospective cohort, we included consecutive adult patients who underwent Allo-HCT at a single center between 2016 and 2020. CMV-seronegative recipients allografted with CMV-seronegative donors, those receiving anti-CMV prophylaxis, or patients who died before D+30 after transplant were excluded. The study received the local Institutional Review Board approbation. Patients underwent weekly surveillance for CMV DNAemia by a CMV real-time polymerase chain reaction (PCR) kit (produced by Qiagen; CMV amplification Reagent kit, Abbott) in plasma. The screening started in the first week after SCT and was repeated weekly until D+100 and after D+100 if immunosuppression was maintained. PET was initiated at the treating physician’s discretion. Suggested thresholds were CMV DNAemia of more than 150 IU/ mL for high-risk (cord-blood, haploidentical, HLA-mismatched, or T-cell depleted allo-HCT or receiving >1mg/kg corticosteroids) patients and more than 500 IU/mL for low-risk patients (not meet high-risk criteria) [5]. (Val)gancyclovir is standard PET unless the episode occurs before engraftment or during neutropenia, in these cases Foscarnet is the drug of choice [4]. Patients with pre-engraftment CMV DNAemia were compared with post-engraftment CMV DNAemia regarding viremia clearance, time to engraftment, and overall mortality D+100 and 1-year post HCT. Engraftment was defined as absolute neutrophil count >500 cells/mm on 3 consecutive days. Clinically significant CMVi (csCMVi) was defined as CMV disease or CMV DNAemia leading to PET [4]. Viremia clearance was defined as the interval from the date of the initiation of PET to clearance. During the study, 111 stem cell transplant patients were enrolled, with a median age of 40 years (ranging from 18 to 72 years old). CMV seropositivity was found in 95% of recipients. Haploidentical, unrelated, and fully matched related donors were 45 (40%), 33 (30%), and 33 (30%), respectively. The time to engraftment from infusion was D+17 (+2–+41), the median follow-up was 235 days (33–1604), and 78% of our patients had a follow-up longer than 100 days. CMV DNAemia and csCMVi were documented in 99 (89%) and 81 (73%) patients, respectively. Tissue-invasive disease occurred in 7 patients (5 gastrointestinal, 1 pneumonia, and 1 bladder disease). Pre-engraftment CMV DNAemia was seen in 42 patients, and 57 patients had CMV DNAemia after engraftment (58%). PET was started in 29 and 47 (69% vs. 82%, p= 0.15) of CMV DNAemia before and after engraftment. The reasons for not treat CMV DNAemia were <150 UI/mL or a single positive CMV DNAemia. The PET for pre-engraftment CMV DNAemia was mainly started after engraftment (79%). The drug was initiated before engraftment in only three patients, all of whom received foscarnet. In the other three, ganciclovir was started concomitantly with engraftment. The treatment of pre-engraftment csCMVi was started a median of 24 days after CMV DNAemia was first documented. In patients with post-engraftment csCMVi, the median time to start therapy was 12 days (p < 0.001). The patients’ clinical characteristics and virological features are detailed in Table 1. Pre-engraftment CMV DNAemia was associated with prolonged time to engraftment (median time to engraftment was 20 vs. 16 days; p= 0.02, by log-rank) than post-engraftment CMV DNAemia (Supplementary Fig. S1). In a Cox regression model, pre-engraftment CMV DNAemia (adjusted HR 2.12; p < 0.01) was still a significant risk factor for later engraftment (Supplementary Table S1). D+100 and 1-year OS were 75% vs. 93% and 60% vs. 76% in pre-engraftment CMV DNAemia and post-engraftment CMV DNAemia patients, respectively (p= 0.02, by log-rank) (Supplementary Fig. S2). In multivariate Cox regression, pre-engraftment CMV DNAemia remained an independent prognostic factor (p= 0.02) in a model that included…

Hematology, Transfusion and Cell Therapy, 2020

Blood Cells, Molecules, and Diseases, 2021

Blood, 2007

Between January 2001 and June 2005 a prospective cohort study of hospitalized patients with hemat... more Between January 2001 and June 2005 a prospective cohort study of hospitalized patients with hematological malignancies including 47 adults and 30 children with candidemia was conducted at a tertiary oncology care center in Brazil in order to compare the epidemiological characteristics, concurrent illnesses and the clinical microbiological data of both groups that may influence the outcome. The crude mortality was higher in the adult population than in children (46,8% vs. 20,0%) (figure 1). A univariate analysis indicated that in the adult population were lymphoma, neutropenia, presence of comorbidities, a non-removed central venous catheter (CVC), a poor performance status, lack of CVC, use of steroid, hepatic dysfunction, previous surgery, hypotension and severe respiratory dysfunction were risk factors significantly associated with death. Among children the predictors of mortality were acute leukemia, neutropenia, presence of comorbidities, lack of CVC, poor performance status, hy...

Hematology, Transfusion and Cell Therapy, 2020

The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1... more The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.

Journal of Clinical Oncology, 2007

17068 Background: Patients receiving imatinib had a significant survival advantage compared with ... more 17068 Background: Patients receiving imatinib had a significant survival advantage compared with patients receiving IFN therapy (Roy et al. Blood 2006; Kantarjian et al. Blood 2006). Although reimbursed as second line therapy for CP CML patients who did not respond to INF-a, IM was not considered for public reimbursement as first line treatment in Brazil based on drug costs. An economic evaluation considering the mortality risk reduction with first line IM versus INF was performed under the Brazilian Public Healthcare System perspective, comparing the costs to avoid one death of a chronic phase CML patient over a 5-year period. Methods: Risk of death in 5 years was defined by survival rates in the 60 month follow-up of IRIS for IM (Rim= 10%) (Druker et al. JCO 2006), MD Anderson cohort of CML patients treated with INF-a for INF-a (RINF-a= 38%) (Cortes et al. American J. Med 1996) and a population based-survey in Norway for the natural course of the disease (Rnon-treatment= 67%). IRI...

$Research paper thumbnail of Open-Label Early-Access Programs (EAPs) for Ibrutinib in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia (CLL) or Mantle-Cell Lymphoma (MCL)$

Blood, 2018

Background:Treatment options for patients with relapsed/refractory chronic lymphocytic leukemia (... more Background:Treatment options for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) are limited. Ibrutinib is a first-in-class small-molecule inhibitor of Bruton's tyrosine kinase. These extended access programs (EAP) provided patient access to ibrutinib in Brazil and real-world safety data was collected, at a time when the medication was not commercially available in Brazil. Methods:These two prospective, multicenter, open-label EAPs of single-agent ibrutinib were conducted between April 2013 and August 2017, and enrolled Brazilian patients with relapsed/refractory CLL or MCL. Eligible patients must have progressive disease after at least one prior therapy and not suitable for retreatment with purine analogue therapy. After a 30-day screening, eligible patients received once-daily oral ibrutinib 420 mg (CLL) or 560 mg (MCL) continuously until disease progression, unacceptable toxicity, absence of clinical benefit, or end of EAP, w...

Blood, 2018

Objectives: Chronic lymphocytic leukemia (CLL) presents a heterogeneous clinical course. Treatmen... more Objectives: Chronic lymphocytic leukemia (CLL) presents a heterogeneous clinical course. Treatment mainly aims to control clinical manifestations and improving survival. Some biological markers have significant prognostic value. Cytogenetic studies in CLL have central role to refine the follow-up of disease evolution, to guide treatment options and monitoring response. Due to low mitotic index in conventional cytogenetic studies, fluorescence in situ hybridization (FISH) became an indispensable tool. The main objective of this study was analyze the presence of del(17p13) using FISH and the percentage of positive cells that have impact on survival, along with clinical characteristics from CLL patients. Methods: Seventy-one CLL patients were studied from 2010 to 2017. Median age was 57 years old and male patients were 56,4%. FISH analysis was performed using peripheral blood samples from patients and TP53 spectrum srange/CEP 17 spectrum green probe (Vysis). Statistical analysis was pe...

Hematology, Transfusion and Cell Therapy, 2020

International Journal of Gynecology & Obstetrics, 2009

Blood, Dec 7, 2017

International Journal of Stem Cells, 2021

Oral Diseases, 2021

Hematology, Transfusion and Cell Therapy, 2020

Bone Marrow Transplantation, 2021

Hematology, Transfusion and Cell Therapy, 2020

Blood Cells, Molecules, and Diseases, 2021

Blood, 2007

Hematology, Transfusion and Cell Therapy, 2020

Journal of Clinical Oncology, 2007

$Research paper thumbnail of Open-Label Early-Access Programs (EAPs) for Ibrutinib in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia (CLL) or Mantle-Cell Lymphoma (MCL)$

Blood, 2018