Publications by authors named "Irene Biasoli"

31 Publications

Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS) questionnaire: translation, cultural adaptation and validation to Brazilian Portuguese.

Hematol Transfus Cell Ther 2021 Jan 3. Epub 2021 Jan 3.

Faculdade de Ciências Médicas, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Introduction: Constitutional symptoms and thrombohemorrhagic events are common in patients with myeloproliferative neoplasms (MPNs). Hence, the treatment's primary goal is to control symptoms and improve the quality of life (QoL). In order to assess response to therapy, symptom burden, and QoL among patients with MPN, the "Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)" questionnaire was developed in the USA in 2012. Herein, we translated and validated the MPN-SAF TSS questionnaire to Brazilian Portuguese.

Methods: The ten-item questionnaire was translated from the English language and its psychometric properties (reliability, convergent and construct validities) were evaluated in 101 MPN patients.

Results: There were 41 patients with essential thrombocythemia, 39 with myelofibrosis and 21 with polycythemia vera. The median age of all patients at diagnosis was 68 years and 59% were female. The Cronbach's alpha coefficient for the overall questionnaire was 0.78, ranging from 0.73 to 0.79, if each item was deleted. Validity analyses showed that the strongest item-item correlation were between early satiety and abdominal discomfort. Strong correlations were also found between physician and patient perceptions of itching (r=0.81) and fatigue (r=0.70). The Pearson coefficient correlation between the MPN-SAF TSS global score and the EORTC QLQ-C30 functional scales ranged from 0.51 to 0.64. The exploratory factor analysis showed that seven of the ten symptoms loaded into one single factor.

Conclusion: The Brazilian Portuguese version of the MPN-SAF-TSS showed good psychometric properties and can be an available tool to assess symptom burden in this group of patients.
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http://dx.doi.org/10.1016/j.htct.2020.10.966DOI Listing
January 2021

How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation.

Hematol Transfus Cell Ther 2020 Apr - Jun;42(2):103-110. Epub 2020 Apr 17.

FCM da Santa Casa de São Paulo, São Paulo, SP, Brazil; Hospital Samaritano Higienópolis, São Paulo, SP, Brazil.

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.
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http://dx.doi.org/10.1016/j.htct.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164906PMC
April 2020

Resources-Stratified Guidelines for Classical Hodgkin Lymphoma.

Int J Environ Res Public Health 2020 03 9;17(5). Epub 2020 Mar 9.

Institute of Global Health, Faculty of Medicine, University of Geneva, Campus Biotech, Chemin des Mines 9, 1202 Geneva, Switzerland.

Hodgkin lymphoma is a haematological malignancy predominantly affecting young adults. Hodgkin lymphoma is a highly curable disease by current treatment standards. Latest treatment guidelines for Hodgkin lymphoma however imply access to diagnostic and treatment modalities that may not be available in settings with restricted healthcare resources. Considerable discrepancies in Hodgkin lymphoma patient survival exist, with poorer outcomes reported in resources-constrained settings. Resources-stratified guidelines for diagnosis, staging and treatment of Hodgkin lymphoma were derived in an effort to optimize patient outcome provided a given setting of available resources. These guidelines were derived based on the framework of the Breast Health Global Initiative stratifying resource levels in basic, core, advanced and maximal categories.
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http://dx.doi.org/10.3390/ijerph17051783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084688PMC
March 2020

Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas.

Am J Hematol 2020 02 25;95(2):151-155. Epub 2019 Nov 25.

CHIMOMO Department University of Modena and Reggio Emilia, Modena, Italy.

The T Cell Project was the largest prospective trial to explore the incidence, treatment patterns, and outcomes for T cell lymphomas. The rare subtypes of T cell lymphomas, including hepatosplenic T cell lymphoma (HSTCL), enteropathy associated T cell lymphoma (EATL), and peripheral gamma delta T cell lymphomas (PGDTCLs) are poorly represented in most studies and there is little data regarding treatment patterns. We report results from 115 patients with hepatosplenic (n = 31), enteropathy associated (n = 65), and PGDTCLs (n = 19). While anthracycline regimens were most commonly used as first line therapy, response rates ranged from 20%-40% and were suboptimal for all groups. Autologous stem cell transplantation was performed as a consolidation in first remission in a small number of patients (33% of HSTCL, 7% of EATL, and 12% of PGDTCL), and four patients with HSTCL underwent allogeneic stem cell transplantation in first remission. The progression free survival at 3 years ranged from 28%-40% for these rare subtypes, and the overall survival at 3 years was most favorable for PGDTCL (70%). These data highlight the need for novel treatment approaches for rare subtypes of T cell lymphomas and for their inclusion in clinical trials.
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http://dx.doi.org/10.1002/ajh.25674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025136PMC
February 2020

The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project.

Haematologica 2018 07 29;103(7):1191-1197. Epub 2018 Mar 29.

Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.

This analysis explored factors influencing survival of patients with primary refractory and relapsed peripheral T-cell lymphomas enrolled in the prospective International T-cell Project. We analyzed data from 1020 patients with newly diagnosed disease, enrolled between September 2006 and December 2015. Out of 937 patients who received first-line treatment, 436 (47%) were identified as refractory and 197 (21%) as relapsed. Median time from the end of treatment to relapse was 8 months (range 2-73). Overall, 75 patients (8%) were consolidated with bone marrow transplantation, including 12 refractory and 22 relapsed patients. After a median follow up of 38 months (range 1-96 months) from documentation of refractory/relapsed disease, 440 patients had died. The median overall survival (OS) was 5.8 months; 3-year overall survival rates were 21% and 28% for refractory and relapsed patients, respectively (<0.001). Patients receiving or not salvage bone marrow transplantation had a 3-year survival of 48% and 18%, respectively (<0.001). In a univariate Cox regression analysis, refractory disease was associated with a higher risk of death (HR=1.43, =0.001), whereas late relapse (>12 months, HR 0.57, =0.001) and salvage therapy with transplantation (HR=0.36, <0.001) were associated with a better OS. No difference was found in OS with respect to histology. This study accurately reflects outcomes for patients treated according to standards of care worldwide. Results confirm that peripheral T-cell lymphomas patients had dismal outcome after relapse or progression. Patients with chemotherapy sensitive disease who relapsed after more than 12 months might benefit from consolidation bone marrow transplantation.
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http://dx.doi.org/10.3324/haematol.2017.186577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029527PMC
July 2018

Lower socioeconomic status is independently associated with shorter survival in Hodgkin Lymphoma patients-An analysis from the Brazilian Hodgkin Lymphoma Registry.

Int J Cancer 2018 03 26;142(5):883-890. Epub 2017 Oct 26.

School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

Socioeconomic status (SES) is a well-known determinant of outcomes in cancer. The purpose of this study was to analyze the impact of the SES on the outcomes of Hodgkin lymphoma (HL) patients from the Brazilian Prospective HL Registry. SES stratification was done using an individual asset/education-based household index. A total of 624 classical HL patients with diagnosis from January/2009 to December/2014, and treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine), were analyzed. The median follow-up was 35.6 months, and 33% were classified as lower SES. The 3-year progression- free survival (PFS) in higher and lower SES were 78 and 64% (p < 0.0001), respectively. The 3-year overall survival (OS) in higher and lower SES were 94 and 82% (p < 0.0001), respectively. Lower SES patients were more likely to be ≥ 60 years (16 vs. 8%, p = 0.003), and to present higher risk International Prognostic score (IPS) (44 vs. 31%, p = 0.004) and advanced disease (71 vs. 58%, p = 0.003). After adjustments for potential confounders, lower SES remained independently associated with poorer survival (HR = 3.12 [1.86-5.22] for OS and HR = 1.66 [1.19-2.32] for PFS). The fatality ratio during treatment was 7.5 and 1.3% for lower and higher SES (p = 0.0001). Infections and treatment toxicity accounted for 81% of these deaths. SES is an independent factor associated with shorter survival in HL in Brazil. Potential underlying mechanisms associated with the impact of SES are delayed diagnosis and poorer education. Educational and socio-economic support interventions must be tested in this vulnerable population.
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http://dx.doi.org/10.1002/ijc.31096DOI Listing
March 2018

New agents in relapsed/refractory Hodgkin's lymphoma.

Rev Bras Hematol Hemoter 2017 Jul - Sep;39(3):193-196. Epub 2017 May 28.

Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.

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http://dx.doi.org/10.1016/j.bjhh.2017.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568577PMC
May 2017

Treatment outcomes for Hodgkin lymphoma: First report from the Brazilian Prospective Registry.

Hematol Oncol 2018 Feb 23;36(1):189-195. Epub 2017 Jun 23.

School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web-based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkin's Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years. Multivariate Cox regression models were used to estimate progression-free (PFS) and overall survival (OS) by clinical factors. A total of 674 patients with classical HL were analysed, with a median follow-up of 37 months. Median age was 30 years (13-90). The median time from the onset of symptoms to diagnosis was 6 months (0-60). Only 6% of patients had early favourable disease, while 65% had advanced disease. Stage IVB was present in 26% and a high-risk International Prognostic Score in 38%. Doxorubicin, bleomycin, vinblastine, and dacarbazine was used in 93%. The median dose of radiotherapy was 36 Gy for localized disease and 32 Gy for advanced disease. The 3 year PFS in early favourable, early unfavourable, and advanced disease were 95%, 88%, and 66%, respectively. High-risk International Prognostic Score, advanced disease, and age greater than or equal to 60 were independently associated with poorer PFS and OS; performance status greater than or equal to 2 was also associated with a poorer OS. Poor-risk patients predominated. Radiation doses for localized disease appear higher than current recommendations. Outcomes appear inferior in developing countries than in developed countries. Delayed diagnosis is probably a major factor underlying these findings. Scattered reports from developing nations suggest that many aspects of standard care in developed countries remain unmet needs for populations living in developing countries. The present report contributes to this body of data, with a proper description of what is currently achieved in urban areas in Brazil.
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http://dx.doi.org/10.1002/hon.2450DOI Listing
February 2018

Monoclonal B-cell lymphocytosis.

Rev Bras Hematol Hemoter 2015 Sep-Oct;37(5):285-6. Epub 2015 Aug 8.

Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.

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http://dx.doi.org/10.1016/j.bjhh.2015.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685083PMC
September 2015

Molecular responses at 3 and 6 months after switching to a second-generation tyrosine kinase inhibitor are complementary and predictive of long-term outcomes in patients with chronic myeloid leukemia who fail imatinib.

Leuk Lymphoma 2015 Jun 20;56(6):1787-92. Epub 2014 Nov 20.

HEMORIO , Rio de Janeiro , Brazil.

Early molecular response (MR) defined by BCR-ABL(IS) levels has prognostic impact in chronic myeloid leukemia (CML). MR was evaluated at 3 and 6 months after switching to nilotinib or dasatinib in 115 patients with resistance to imatinib. Three groups were delineated at 3 months (< 1%, 1-10% or > 10% BCR-ABL(IS) levels) with different outcomes at 3 years regarding major molecular response (MMR, 91%, 47%, 22%, p < 0.001), failure-free survival (FFS), progression-free survival (PFS, 96%, 89% and 78%, p = 0.05) and overall survival (OS). After 6 months, patients with MR < 1% had higher 3-year MMR (83% vs. 16%, p < 0.001), FFS, PFS (94% vs. 84%, p = 0.05) and OS. Four patients had 3-month and 6-month MR > 10% and < 1%, respectively (3-year FFS 50%). Thirteen had 3-month and 6-month MR < 10% and ≥ 1%, respectively (3-year FFS 38%). These findings confirm the strong predictive value of 3-month and 6-month BCR-ABL(IS) levels in imatinib-resistant patients.
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http://dx.doi.org/10.3109/10428194.2014.974047DOI Listing
June 2015

Prognostic value of PET-CT after first-line therapy in patients with follicular lymphoma: a pooled analysis of central scan review in three multicentre studies.

Lancet Haematol 2014 Oct 17;1(1):e17-27. Epub 2014 Sep 17.

Service de Médecine Nucléaire, Hôpital Henri Mondor and Université Paris Est Créteil, Créteil, France.

Background: The value of (18)F-fluorodeoxyglucose (FDG) PET-CT (PET) imaging in response assessment after first-line rituximab chemotherapy for follicular lymphoma has been documented. We analysed the application of the five-point Deauville scale (5PS; used to score FDG uptake on PET images) in a large cohort derived from three studies, to assess the correlation between post-induction PET status and survival in patients with follicular lymphoma.

Methods: In this pooled analysis, we used data from three multicentre prospective studies of first-line rituximab chemotherapy for patients with high-tumour-burden follicular lymphoma (the PRIMA study, the PET-Folliculaire study, and the Fondazione Italiana Linfomi FOLL05 study). Patients included in this analysis received at least six cycles of rituximab and chemotherapy before response assessment with conventional contrast-enhanced CT and PET low-dose CT (PET). We included only patients who had a PET scan within 3 months of the last dose of induction rituximab. Patient data, including conventional CT-based response assessment, were recorded for all patients undergoing PET review. Scans undergoing central PET review were scored independently by three reviewers according to the 5PS. The primary endpoints were progression-free survival and overall survival according to the 5PS score of post-induction PET scan (ie, positive [≥4 points] or negative [<4 points]), analysed in the central review population.

Findings: Between Dec 24, 2004, and Sept 22, 2010, 439 of the patients enrolled in the three studies underwent local PET assessment, 246 of whom had centrally reviewed post-induction scans. 41 (17%) of 246 patients had a positive post-induction PET scan according to a cutoff of 4 or higher on the 5PS, with substantial reporter concordance. With a median follow-up of 54·8 months (IQR 39·7-68·5; range 7·7-90·1), the hazard ratio (HR) for progression-free survival for patients with a positive PET scan versus those with a negative PET scan was 3·9 (95% CI 2·5-5·9; p<0·0001), and for overall survival was 6·7 (2·4-18·5; p=0·0002). For patients with a positive PET scan, 23·2% (95% CI 11·1-37·9) of patients were progression free at 4 years compared with 63·4% (55·9-70·0) of those who had a negative PET scan (p<0·0001); 4-year overall survival was 87·2% (95% CI 71·9-94·5) versus 97·1% (93·2-98·8), respectively (p<0·0001). Conventional CT-based response (ie, complete response or unconfirmed complete response vs partial response) was weakly predictive of progression-free survival (HR 1·7 [95% CI 1·1-2·5]; p=0·017).

Interpretation: PET-CT rather than contrast-enhanced CT scanning should be considered as a new standard for response assessment of follicular lymphoma in clinical practice, and could help guide response-adapted therapy.

Funding: Groupe d'Etude des Lymphomes de l'Adulte (Paris, France), now LYSA (Lymphoma Study Association), Direction de la Recherche Clinique de l'Assistance Publique-Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health.
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http://dx.doi.org/10.1016/S2352-3026(14)70008-0DOI Listing
October 2014

Dismal outcome of T-cell lymphoma patients failing first-line treatment: results of a population-based study from the Modena Cancer Registry.

Hematol Oncol 2015 Sep 29;33(3):147-51. Epub 2014 Apr 29.

Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica, Università di Modena e Reggio Emilia, Modena, Italy.

We conducted a population-based study to establish the outcome of T-cell lymphoma (TCL) patients failing systemic first-line therapy. All TCL patients failing first-line systemic therapy in the province of Modena were identified from Modena Cancer Registry between 1997 and 2010. A total of 53 patients were analysed. Regarding the type of failure, 18 patients relapsed, and 35 progressed during first treatment. Among relapsed patients, the median time from date of response to relapse after first treatment was 6.2 months (range 1.87-102). A total of 18 patients (34%) died before receiving salvage treatment, 21 received platinum or gemcitabine-containing regimens (7 addressed to autologous stem cell transplant (ASCT)), 12 other CT regimens; 2 received radiotherapy (RT). The median survival after relapse (SAR) was 2.5 months. After a median follow-up for living patients after failure of 35 months (range 8-111 months), 44 patients died, and the cause of death was found to be lymphoma progression in all (98%) but one of them. The median SAR was 2.5 months. The 3-year SAR was 19%. Univariate and multivariate Cox regression analyses for SAR were performed. In multivariate analysis, performance status and type of failure were associated with a higher risk of death after relapse. The outcome of TCL patients failing first-line therapy is poor. Only a few cases that could receive ASCT had promising chances of long remission. There is urgent need for novel agents for patients requiring second-line treatment.
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http://dx.doi.org/10.1002/hon.2144DOI Listing
September 2015

Follicular lymphoma - treatment and prognostic factors.

Rev Bras Hematol Hemoter 2012 ;34(1):54-9

Department of Oncology, Hematology and respiratory diseases, L'Università di Modena e Reggio Emilia - UniMoRe, Modena, Italy.

Follicular lymphoma is the second most frequent non-Hodgkin lymphoma accounting for about 10-20% of all lymphomas in western countries. The median age at diagnosis is 60 years old. The clinical presentation is usually characterized by asymptomatic peripheral adenopathy in cervical, axillary, inguinal and femoral regions. Treatment options for patients with naïve or recurrent follicular lymphoma are still controversial, ranging from a "watch and wait" policy to hematopoietic stem cell transplantation. More recently, the availability of rituximab has substantially changed follicular lymphoma therapeutic approaches to such an extent that R-Chemo is now the standard induction first-line treatment. This review provides a general overview of the state of the art in the management of follicular lymphoma and also, a brief description regarding the current prognostic tools available for treatment decisions.
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http://dx.doi.org/10.5581/1516-8484.20120015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459616PMC
October 2012

Fertility in female survivors of Hodgkin's lymphoma.

Rev Bras Hematol Hemoter 2012 ;34(1):48-53

Hematology and Pathology Services, Hospital Universitário, Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil.

Currently, Hodgkin's lymphoma is one of the most curable types of cancer. Patients are often young and so the long-term morbidities of treatment have become of increasing concern. Among these, infertility is one of the most challenging consequences for patients in reproductive age. Premature ovarian failure in premenopausal women is a serious long-term sequel of the toxicity of chemotherapy. The main consequence of this syndrome is infertility, but women also present other symptoms related to estrogen deprivation. Different rates of impaired gonadal function are reported, depending on the patient's age, stage of disease, dose and intensity of chemotherapy and the use of radiation therapy. The most established strategy in female infertility is cryopreservation of embryos after in vitro fertilization. Additionally, the use of oral contraceptives or gonadotropinreleasing hormone analogs (GnRH-a) during treatment is under study. This review will provide a general overview of the main studies conducted to evaluate the infertility rate among female Hodgkin's lymphoma survivors and risk factors associated to treatment, different end-point definitions for evaluating fertility and also a brief description of the available strategies for fertility preservation.
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http://dx.doi.org/10.5581/1516-8484.20120014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459604PMC
October 2012

Risk factors for impaired gonadal function in female Hodgkin lymphoma survivors: final analysis of a retrospective multicenter joint study from Italian and Brazilian Institutions.

Hematol Oncol 2013 Jun 2;31(2):72-8. Epub 2012 Oct 2.

Dipartimento di Ematologia, Ospedale Civile Spirito Santo, Pescara, Italy.

Hodgkin lymphoma (HL) is one of the most common types of cancer in the young and one of the most curable forms of cancer. Therefore, there has been an increasing interest in the study of long-term morbidities. The aims of the present study were to evaluate the prevalence and risk factors for impaired gonadal function in a retrospective cohort of 238 HL female survivors from Italy and Brazil and to analyse the role of oral contraceptives (OC) and GnRH-analogues. Besides data collection from HL databases, a specific questionnaire was administered to collect data on gonadal function. The median age at diagnosis was 25 years and the median follow-up was 7 years. Overall, 25% of the patients developed impaired gonadal function. Older age at diagnosis, front-line therapies containing alkylating agents and more than one treatment were independent risk factors, whereas the use of OC or GnRH-a reduced independently the risk of impaired gonadal function. The fertility rate among fertile survivors was low when compared with the general population. We confirmed that older age, type of front-line chemotherapy and a higher number of therapies are associated with gonadal function impairment in terms of infertility and premature menopause in female HL survivors. Also, the use of GnRH-a or OC was independently identified as a protective factor. Further prospective studies are needed to better understand the barriers to parenthood in HL survivors.
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http://dx.doi.org/10.1002/hon.2029DOI Listing
June 2013

CD137 is expressed in follicular dendritic cell tumors and in classical Hodgkin and T-cell lymphomas: diagnostic and therapeutic implications.

Am J Pathol 2012 Sep;181(3):795-803

Department of Pathology, Stanford University School of Medicine, California, USA.

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.
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http://dx.doi.org/10.1016/j.ajpath.2012.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432425PMC
September 2012

Psychometric properties of the multidimensional fatigue inventory in Brazilian Hodgkin's lymphoma survivors.

J Pain Symptom Manage 2012 Dec 13;44(6):908-15. Epub 2012 Jun 13.

Hematology and Pathology Services, University Hospital, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Context: Fatigue is the most common symptom among Hodgkin's lymphoma survivors.

Objectives: To evaluate the psychometric properties of the Brazilian version of the Multidimensional Fatigue Inventory (MFI).

Methods: The MFI was translated into Brazilian Portuguese using established forward-backward translation procedures, and the psychometric properties were evaluated in a sample of 200 Hodgkin's lymphoma survivors. The psychometric properties evaluated included internal consistency and construct validity. The MFI was administered along with the informed consent form.

Results: The overall Cronbach's alpha coefficient for the 20 items was 0.84, ranging from 0.59 to 0.81 for each of the five scales. Correlations between items and scales ranged from 0.32 to 0.72. The factor analysis yielded a five-factor solution that explained 65% of the variance. The first factor merged the original "general fatigue" and "physical fatigue" scales, as has been previously reported. The second factor identified the original "mental fatigue" scale and the fifth factor identified the original "reduced activity" scale. Questions from the original "reduced motivation" scale were represented in both factors three and four.

Conclusion: The Brazilian version of the MFI showed satisfactory psychometric properties and can be considered a valid research tool for assessing cancer-related fatigue.
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http://dx.doi.org/10.1016/j.jpainsymman.2011.12.275DOI Listing
December 2012

Validation of the Brazilian Portuguese version of the Medical Outcomes Study-Social Support Survey in Hodgkin's lymphoma survivors.

Support Care Cancer 2012 Aug;20(8):1895-900

Hematology and Pathology Services, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

Purpose: The aim of this study was to assess the psychometric properties of the Brazilian Portuguese version of the “Medical Outcomes Study-Social Support Survey (MOS-SSS)” in Hodgkin's lymphoma (HL) survivors.

Methods: The MOS-SSS is a 19-item questionnaire with five scales covering different aspects of social support (affection, positive social interaction, emotional, informational, and material). A sample of 200 HL survivors completed a self-administered questionnaire at the treatment center or at home.

Results: The median age of the patients at diagnosis was 29 years (16–77), and the median follow-up since diagnosis was 7 years (3.6-12.7). Item-corrected Pearson correlation coefficients between items and their dimensions varied from 0.57 to 0.76. Internal consistency, evaluated using Cronbach's alpha, was 0.95 for the overall scale, ranging from 0.78 to 0.87 for the five subscales proposed by the original instrument. An exploratory factor analysis yielded a three-factor solution, aggregating affection and positive social interaction, and emotional and informational dimensions of social support. Higher socioeconomic status and higher social network were associated with higher levels of all kinds of support.

Conclusion: Results show good general psychometric properties of the Brazilian version of the MOS-SSS when applied to HL survivors. The three-factor structure identified in this study is in line with a previous validation among Brazilian healthy civil servants. The Brazilian Portuguese version will now be used to evaluate social support and its association with long-term disease outcomes and quality of life of Hodgkin's lymphoma survivors.
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http://dx.doi.org/10.1007/s00520-011-1292-8DOI Listing
August 2012

Changing patterns of AIDS: impact on the indications and diagnostic yield of bone marrow biopsies.

Braz J Infect Dis 2010 Jul-Aug;14(4):419-21

Hospital Universitário, Universidade Federal do Rio de Janeiro, Brazil.

After the advent of HAART, the clinical course of HIV infection has dramatically improved. Therefore, it seems appropriate to reevaluate the performance of bone marrow biopsy (BMB) as a diagnostic tool. The aim of the present study was to compare the reasons for performing a BMB and its diagnostic yield in HIV-patients before and after HAART. A total of 165 BMB specimens obtained from HIV-infected patients receiving care at the Hospital of Universidade Federal do Rio de Janeiro in two different periods (1986-1994 and 1999-2004) were analysed. The main reason for BMB examination in the first period was fever (88%), which decreased in the second period (57%, p < 0.0001), when cytopenia (51%) was the leading reason for BMB, whereas in the first period it accounted for only 30% (p = 0.008). A definitive diagnosis (infection, granulomas or lymphomas) was obtained in 28% of patients in the first period and in 19% during the second period (p = 0.20). The diagnosis turned out as infections decreased from 16% in period 1 to 2% in period 2 (p = 0.003). Despite the the limitations in the evaluation of fever, the use of BMB must be considered on an individual basis, whenever less invasive alternatives have been exhausted, and should be complemented by a bone marrow aspiration for microbiological studies.
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March 2011

Nodular, lymphocyte-predominant Hodgkin lymphoma: a long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group.

Cancer 2010 Feb;116(3):631-9

Hematology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Nodular, lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a rare entity.

Methods: A clinical registry was launched from 1973 to 2003 in France. To determine the histologic transformation (HT) rate to diffuse large B-cell lymphoma (DLBCL) and long-term outcomes, 164 patients were selected after histologic review.

Results: The median follow-up was 9.5 years. The high biopsy rate (85%) at each recurrence enabled the analysis of HT. The median patient age was 30 years (range, 6-69 years), 80% of patients were men, 83% had Ann Arbor stage I/II disease, 65% had supradiaphragmatic-disease; 27% received radiotherapy, 9% received chemotherapy, 29% received combined-modality therapy, and 35% were followed with a watch-and-wait strategy. All 106 treated patients achieved complete remission and 66 patients developed disease recurrence at a median of 3.3 years (range, 0.4-18.3 years after diagnosis). The majority of recurrences were NLPHL, but 19 patients progressed to DLBCL at a median of 4.7 years (range, 0.4-18 years after diagnosis). The 10-year cumulative HT rate was 12% and was found to be associated significantly with a poor prognosis. The 10-year overall survival rate was 91%. Fourteen patients died (7 died of progressive disease, 3 died of secondary cancers, and 4 died from other causes). HT was diagnosed at a median of 4.7 years (range, 0.4-18 years after diagnosis). The 19 patients who had HT were treated with curative intent: Nine patients received high-dose therapy with subsequent autologous stem cell transplantation (ASCT), and 10 patients received different chemotherapy regimens. The overall survival rate after HT did not differ between patients who underwent ASCT and the others.

Conclusions: This long-term follow-up study confirmed that NLPHL is a separate entity that has a favorable clinical presentation and outcome despite frequent recurrences. The current findings also emphasize the importance of biopsies at the time patients develop recurrent disease to evaluate HT.
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http://dx.doi.org/10.1002/cncr.24819DOI Listing
February 2010

Human germinal center-associated lymphoma protein expression is associated with improved failure-free survival in Brazilian patients with classical Hodgkin lymphoma.

Leuk Lymphoma 2009 Nov;50(11):1830-6

Pathology and Oncology Services, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.

The human germinal center-associated lymphoma (HGAL) gene has prognostic value in diffuse large B-cell lymphoma, and expression of its cognate protein is germinal center-specific. A previous study had suggested that HGAL protein expression might also be related to the outcome in patients with Hodgkin lymphoma (HL). The aim of this study was to confirm the prognostic impact of HGAL protein expression in an independent, well-characterized cohort of 232 patients with classic HL treated uniformly with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). Tissue microarray analysis showed HGAL staining in 188 specimens (81%). Failure-free survival (FFS) was superior in patients with early-stage disease, low-risk IPS, and HGAL-positive patients. The estimated 5-year FFS for HGAL-positive and HGAL-negative patients was 82% and 67%, respectively (p = 0.03). In the multivariate analysis, advanced stage and absence of HGAL staining were independent predictors of a worse FFS. This study confirms and validates recent findings of a correlation between HGAL expression and outcome in classical HL.
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http://dx.doi.org/10.3109/10428190903242628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882884PMC
November 2009

Evaluation of intra- and interobserver agreement and its clinical significance for scoring bcl-2 immunohistochemical expression in diffuse large B-cell lymphoma.

Pathol Int 2008 Sep;58(9):596-600

Hematology and Pathology Services, University Hospital, Federal University of Rio de Janeiro, Brazil.

Immunohistochemistry (IHC) has become an essential part of diagnosis and clinical research in lymphomas. There is considerable heterogeneity, however, in IHC findings regarding expression rate and positivity cut-offs, which creates a degree of uncertainty that has prevented its incorporation for prognostic purposes. The purpose of the present study was to assess intra- and interobserver agreement in scoring bcl-2 expression on IHC. The study materials were 81 diffuse large B-cell lymphomas. Slides were processed in the same laboratory, and were analyzed independently and in a blinded manner by four pathologists twice, at least 1 month apart. The positivity rates ranged from 31% to 41% in the first evaluation, and from 30% to 43% in the second evaluation. The two analyses by the same pathologist gave concordant results in 88-93% of cases (kappa = 0.71-0.83). Complete agreement among all observers varied from 72% to 79%. The experience of the observer did not influence intra-observer concordance. Cooperative analysis of discordant slides led to consensus in all cases. The variation observed in scoring bcl-2 expression is acceptable for use in lymphoma diagnosis and classification. The use of IHC stratification, however, for clinical decisions regarding treatment will require standardization and centralized consensus review, and must await the results of ongoing prospective trials.
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http://dx.doi.org/10.1111/j.1440-1827.2008.02276.xDOI Listing
September 2008

Immunoblastic morphology in diffuse large B-cell lymphoma is associated with a nongerminal center immunophenotypic profile.

Leuk Lymphoma 2007 May;48(5):892-6

Pathology Division & Molecular Biology Laboratory, National Cancer Center, Rio de Janeiro, Brazil.

Diffuse large B cell lymphomas (DLCBL) are a group of lymphomas whose biologic and prognostic diversity has been recently well characterized. There is also morphologic heterogeneity, but the relevance of subclassification remains uncertain. The World Health Organization Classification states that pathologists have the choice to use only the term diffuse large B-cell lymphoma or to use one of the specific morphologic variants. The aim of the present study was to evaluate if there is an association between immunoblastic morphology and the immunophenotypic profile in DLBCL. Two observers reviewed 117 DLBCL cases. Cases of immunoblastic lymphoma and cases of centroblastic polymorphic lymphoma with more than 50% immunoblasts were defined as having immunoblastic morphology. Immunohistochemistry was performed on tissue microarray slides to establish the immunophenotypic profile. Patients with immunoblastic morphology more frequently had a non-GCB phenotype (94% vs 6%). This finding suggests that the morphological subclassification of DLBCL does have biological meaning, in line with recent evidence indicating that the immunoblastic morphology should not be overlooked in lymphoma classification.
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http://dx.doi.org/10.1080/10428190701286470DOI Listing
May 2007

A phase II study of second-line neoadjuvant chemotherapy with capecitabine and radiation therapy for anthracycline-resistant locally advanced breast cancer.

Am J Clin Oncol 2007 Feb;30(1):78-81

Oncology and Pathology Services, National Cancer Institute, Rio de Janeiro, Brazil.

Objective: According to data from Brazil's National Cancer Institute nearly 30% of the new patients who present with breast cancer have locally advanced disease. These patients are inoperable and tumor reduction is usually attempted with chemotherapy. First-line anthracyclin-based neoadjuvant chemotherapy is often effective; however, about 30% of the patients fail and to date there is no established second-line treatment. We have studied the concomitant use of radiation therapy and capecitabine in this setting, to determine the toxicity and efficacy of this regimen as a second-line neoadjuvant treatment.

Patients And Methods: Twenty-eight patients with inoperable locally advanced breast cancer refractory to first-line anthracycline based treatment were enrolled between January 2003 and May 2004. Patients received radiation therapy (total dose 5000 cGy) and concomitant capecitabine (850 mg/m2) twice daily for 14 days every 3 weeks.

Results: This treatment rendered 23 of the 28 patients (82%) operable. The 5 remaining patients did not undergo surgery because of disease progression. The median clinical tumor size decreased from 80 cm2 to 49 cm2. Microscopic residual disease was observed in 3 patients (13%) and another patient achieved a complete pathologic response. The median number of involved lymph nodes was 2 and treatment was well tolerated with no grade 3 or 4 events.

Conclusion: Our data indicate that second-line neoadjuvant treatment with radiation therapy and capecitabine is feasible, well tolerated, and effective in patients with locally advanced breast cancer refractory to primary anthracycline-based treatment. These results suggest that a randomized study should be done to compare radiotherapy alone to capecitabine combined with radiotherapy.
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http://dx.doi.org/10.1097/01.coc.0000245475.41324.6dDOI Listing
February 2007

PKC-beta II expression has prognostic impact in nodal diffuse large B-cell lymphoma.

Mod Pathol 2007 Mar 19;20(3):326-30. Epub 2007 Jan 19.

Department of Internal Medicine/Hematology, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Recent studies of gene expression and immunohistochemistry have shown that protein kinase C-beta II (PKC-beta II) might have prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL). We sought to determine the prognostic significance of the expression of PKC-beta II in patients with nodal DLBCL. Formalin-fixed, paraffin-embedded tissues were stained with a monoclonal antibody to PKC-beta II protein. A total of 125 patients were studied; 83 patients (66%) were in the low-risk International Prognostic Index (IPI) group. Forty-eight patients (38%) were positive for PKC-beta II. Complete remission was obtained in 70%, and was not influenced by the PKC-beta II status (67 vs 71%). The 5-year event-free survival (EFS) was worse in high-risk patients (14 vs 58%, P<0.001) and in those with PKC-beta II positivity (36 vs 49%, P=0.054). In low-risk IPI patients, PKC-beta II expression was related to a worse 5-year overall survival (OS) (60 vs 76%, P=0.033) and a worse 5-year EFS (48 vs 66%, P=0.014). In a Cox regression analysis for EFS, both PKC-beta II expression (hazard ratio=1.68, P=0.037) and the IPI (HR=3.07, P<0.001) were independent poor prognostic factors. PKC-beta II (HR=1.72, P=0.046) and the IPI (HR=5.16, P<0.001) were also independent poor prognostic factors for the OS. PKC-beta II expression, along with the IPI, were associated with a worse EFS and OS in patients with nodal DLBCL specially in low-risk IPI patients.
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http://dx.doi.org/10.1038/modpathol.3800738DOI Listing
March 2007

Socioeconomic inequality and short-term outcome in Hodgkin's lymphoma.

Int J Cancer 2007 Feb;120(4):875-9

Hematology and Pathology Services, University Hospital, Federal University of Rio de Janeiro, Brazil.

Socioeconomic status (SES) is a determinant of outcome in various types of cancer. The aim of this study is to analyze the impact of the SES in Hodgkin's lymphoma (HL). From 2001 to 2005, 194 consecutive patients were prospectively followed in 5 institutions. Patients answered a questionnaire with a set of items used to determine the SES, and were then divided in 2 groups according to their SES score. There were 151 patients (78%) with a higher SES and 43 patients (22%) with a lower SES. The complete remission (CR) rate was 82%. Patients with a higher SES had a higher CR rate than those with a lower SES (85 vs. 72%, crude odds ratio = 2.27, p = 0.046). A lower SES and the performance status >1 were independently associated with a trend towards a lower CR, even when controlled for the other covariables of interest. Ten patients (5%) died during treatment. Death during treatment was associated with a lower SES (16 vs. 2%, p = 0.001), a performance status >1 (p < 0.0001), a lower lymphocyte count (p = 0.012) and weakly with a lower albumin level (p = 0.065). With a median follow-up of 1.7 years, a higher SES was associated with a better 2-year overall survival (93 vs. 79%, p = 0.01). In underprivileged countries, patients with a lower SES require a more careful monitoring during treatment, possibly with specific support measures. Regimens more intense than doxorubicin, bleomycin, vinblastine and dacarbazine could pose a prohibitive risk of complications in this group of patients. (c) 2006 Wiley-Liss, Inc.
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http://dx.doi.org/10.1002/ijc.22417DOI Listing
February 2007

Brazilian version of the QLQ-LC13 lung cancer module of the European Organization for Research and Treatment of Cancer: preliminary reliability and validity report.

Qual Life Res 2006 Nov 8;15(9):1519-24. Epub 2006 Sep 8.

Oncology Service, University Hospital, Federal University of Rio de Janeiro, Av. Brigadeiro trompowsky s/no sala 11E17 lloandar, Ilha do Fundão, CEP 21945-560, Rio de Janeiro, Brazil.

This study reports the reliability and validity of the Brazilian Portuguese version of QLQ-LC13. After translation and cross-cultural adaptation, the questionnaire was administered, together with the QLQ-C30 core questionnaire, to 82 patients with lung cancer. The analysis was based on 60 patients who completed two interviews, and who received chemotherapy alone or in combination with radiotherapy. The reliability or internal consistency of dyspnea scale was 0.79. The pain scale needed to be combined with the QLQ-C30 pain items to reach a satisfactory value of 0.73. The construct validity was supported by the ability of the questionnaire to discriminate patients regarding their performance status and type of treatment. However, the change over time, although in the expected direction for all items, was statistically significant in four of the 10 items studied. The criterion-related validity was supported by the statistically significant correlation between all four side effect items and the physicians' reports of toxicity, while the evolutive changes in the performance status were statistically significant in only four items. Most psychometric properties of the Brazilian version of the QLQ-LC13 were adequately supported in this analysis. However, a wider utilization of this module is necessary to fully ascertain its reliability and validity properties.
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http://dx.doi.org/10.1007/s11136-006-0009-9DOI Listing
November 2006

The prognostic value of the expression of Bcl-2, p53 and LMP-1 in patients with Hodgkin's lymphoma.

Leuk Lymphoma 2005 Sep;46(9):1301-6

Hematology Service, School of Medicine and University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

This study was undertaken to evaluate the clinical significance of the expression of Bcl-2, p53 and LMP-1 in Hodgkin and Reed - Sternberg cells of patients with Hodgkin's lymphoma. The expression of these proteins in pre-treatment tissue biopsy specimens was correlated with presenting clinical features, failure-free survival (FFS) and overall survival (OS) in 83 patients with a confirmed Hodgkin's lymphoma treated in a single institution. HIV-positive patients were excluded. Patients were classified according to the International Prognostic Score (IPS) in low-risk (0 - 2 factors) and high-risk groups. The median age was 41 years (15 - 84), 41% were women, and 93% had advanced-stage disease (IIB - IVB). The expression of Bcl-2, p53 and LMP-1 was not associated with the complete remission rate, FFS or OS. The IPS risk group was the only factor significantly associated with OS. Patients with a high IPS had a lower 5 year OS (43% vs. 79%, P = 0.003). The expression of Bcl-2, p53 and LMP-1 did not add prognostic information to the IPS.
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http://dx.doi.org/10.1080/10428190500126034DOI Listing
September 2005