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This is an observational and cross-sectional study, carried out in May 2020, targeting adult individuals of both sexes who are members of multiprofessional teams working in Brazilian HSCT units in the current period of the pandemic by completing and analyzing a questionnaire. pre-formulated. HSCT units that cannot access the questionnaire were excluded from the study. The analysis of the operation profile of HSCT units in Brazil, through the application of a pre-structured questionnaire, is not an accurate tool, since it assumes some premises that may prove to be wrong, especially in this current scenario in Brazil. However, the data reveal the vulnerability of patients with onco-hematological diseases to infection by COVID-19, especially during HSCT procedures, in relation to the general population. Despite its limitations, it can be valuable to plan policies.

Made available in DSpace on 2022-04-29T08:28:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 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. Hospital Israelita Albert Einstein Américas Oncologia AC Camargo Cancer Center Hospital das Clínicas da Faculdade de Medicina de Botucatu (HC-FMB) Instituto do Cancer de São Paulo (ICESP) Hemomed Hospital Municipal da Vila Santa Catarina Universidade de Campinas (UNICAMP) Grupo Oncoclínicas - CTO/CEON Hospital das Clínicas da Universidade Federal de Minas Gerais (HC UFMG) Centro de Cancer de Brasilia CETTRO Hospital Alemão Oswaldo Cruz Universidade Federal de São Paulo (Unifesp) Hospital Sírio Libanês Hospital de Clínicas de Porto Alegre (HPCA) Instituto Nacional do Cancer (INCA) Universidade Federal do Rio de Janeiro (UFRJ) Universidade Federal do Paraná (UFPR) FCM da Santa Casa de São Paulo Hospital Samaritano Higienópolis Hospital das Clínicas da Faculdade de Medicina de Botucatu (HC-FMB)

Objective T-cell Brazil Project was designed as an ambispective data collection from January 2015 to December 2022 of previously untreated patients diagnosed with Peripheral T-cell lymphoma (PTCL) or NK/T-cell lymphoma according to the revised WHO 2017 classification in Brazil. The primary and secondary end points were 2-year overall survival (OS) and progression-free survival (PFS). Clinical, treatment and survival data were also correlated. Methodology Twenty centers got approved for the study from the local and national institutional review board and registered their cases only online. OS was calculated from diagnosis date until last seen or death date, whereas PFS until first event, progression / relapse, date of death or last seen. Kaplan-Meier method was applied and a Log-rank test to compare their curves. P-value less than 5% was considered. From a total of 416 patients with PTCL, 46 (11%) were diagnosed as AITL. Results The median age was 65 years (31-82), with 63% males, 94% had advanced-stage disease. All patients received 61% CHOEP, 28% CHOP and 11% CT without anthracycline. 20% of pts were consolidated with autologous transplant (HSCT). There were 19 (41%) deaths, 10 by lymphoma, 8 infections, 1 new neoplasia. With 8-mo median f/u (1-36), OS at 24-mo was 27% and 2-year PFS was 21%. As consolidation, OS was 71% HSCT group vs. 16% no HSCT (P= 0.06) and PFS was 71% vs. 8%, respectively (P= 0.01). Conclusion These analyses are preliminaries but show a poor outcome of AITL in our population. Most patients were treated with anthracycline-containing combination chemotherapy and just 20% received autologous HSCT. A dismal survival was shown for those who did not receive HSCT.

Introducao O linfoma de celulas do manto (MCL) e um linfoma pouco comum e incuravel, com um comportamento clinico heterogeneo, variando de indolente a muito agressivo. Medicamentos como bortezomibe, temsirolimos, lenalidomida, ibrutinibe e acalabrutinibe foram aprovados para MCL baseados em resultados positivos de estudos clinicos. Alem disto, variacoes de tratamentos habituais como uso de citarabina em altas doses, transplante autologo em primeira remissao e manutencao com rituximabe tambem foram adotados apos estudos clinicos. As agencias regulatorias vem concedendo autorizacao para uso de medicamentos a partir de estudos fase 2 porem, estudos clinicos randomizados fase 3 sao considerados os melhores para gerar evidencias em favor de novos tratamentos. Objetivo Avaliar a qualidade dos estudos clinicos randomizados fase 3 em MCL publicados em revistas indexadas ao PUBMED entre 2011 e 2020. Metodos Efetuamos buscas no pubmed por estudos clinicos de MCL publicados no periodo de 01/01/2011 a 31/12/2020. Foram selecionados apenas os estudos randomizados fase 3. Publicacao posterior foi analisada apenas no caso de mudanca do desfecho primario (1 estudo). Detalhes sobre os estudos selecionados foram pesquisados tambem em www.clinicaltrials.gov . Nosso instrumento de avaliacao de vieses continha 7 dominios (alocacao/randomizacao, desvios das intervencoes pretendidas, dados dos resultados, medicao dos resultados, escolha do braco-controle, crossover apropriado e validade externa) que foram selecionados a partir de dois instrumentos recem-publicados (“A revised tool to assess risk of bias in randomized trials (RoB 2)”em BMJ 2019; 366: l4898 e Prasad e cols. JAMA Intern Med. doi:10.1001/jamainternmed.2020.2250). Resultados Apenas 10 estudos preencheram os criterios para a analise, sendo 3 deles publicados em 2015 (2012-2018). Em 7 estudos, uma industria farmaceutica fabricante do medicamento sendo testado foi patrocinadora. Em 9 estudos, uma nova droga estava sendo testada para a indicacao de MCL. Apenas 1 estudo teve inclusao de pacientes com MCL recaido/refratario. Dois estudos foram para pacientes elegiveis para transplante, 3 para pacientes inelegiveis, 5 incluiram pacientes sem restricoes (3 deles incluiram MCL junto a linfomas indolentes). O uso de crossover foi explicitado em apenas 1 estudo. Quatro estudos foram de nao-inferioridade. O desfecho primario foi sobrevida livre de progressao em cinco, sobrevida global em dois, sobrevida livre de eventos em 1, tempo para o proximo tratamento em 1 e taxa de remissao completa em 1. Todos os estudos foram abertos (sem controle por placebo) e a afericao foi centralizada em 4 estudos. O braco experimental foi melhor em todos os estudos. Detectamos pelo menos 1 vies em 9 estudos (90%). Detectamos vies em ≥ 2 dominios em 6 estudos. Os dominios que mais apresentaram vieses foram: randomizacao seguido de validade externa e dados dos resultados. Apenas um dos estudos resultou em aprovacao para uso em MCL (ibrutinibe). Conclusoes Os estudos randomizados fase 3 para MCL realizados entre 2011 e 2020 foram poucos a despeito do crescente numero de novas drogas sendo aprovadas especificamente para esta doenca. A maioria destes estudos tem vieses de acordo com os parâmetros dos nossos instrumentos de afericao. Alem disto, a heterogeneidade nos criterios de inclusao e nos desfechos principais impede comparacoes entre eles. MCL refratario/recidivado especialmente e uma area carente destes estudos.

Introdução: O papel da terapia de altas doses (TAD) seguida pelo transplante de células tronco periférico (TCTP) autólogo como consolidação é ainda muito discutido para os pacientes com Linfoma de células T periféricas (LCTP), ou seja, não há consenso atualmente sobre o gerenciamento ideal para o tratamento de primeira linha, principalmente devido ao viés de seleção de pacientes e das amostras pequenas nos estudos. Da mesma forma, com a disponibilidade de novos medicamentos, o uso TAD seguida de TCTP na consolidação ou salvamento deixou de serem as únicas opções disponíveis. Assim, nosso objetivo é descrever e verificar os resultados desses procedimentos e compreender o papel da TAD seguida de TCTP nestes pacientes. Métodos: Entre janeiro de 2015 e julho de 2021, 414 pacientes foram registrados por 34 centros brasileiros; destes 374 tinha informação disponível das terapias usadas. Um total de 70 (18.5%) casos foi submetido ao TAD seguido TCTP e este grupo é o foco deste estudo. Sobrevida global (SG) foi calculada a partir da data do diagnóstico até a data da última visita ou data de óbito. A sobrevida livre de progressão (SLP) da data do diagnóstico até data do 1° evento ou última consulta. Para o grupo de salvamento (TCTP-S) foi calculado a SLP considerando a data do TCTP até a data da última consulta ou 1° evento, sendo o evento progressão ou morte. Resultados: A mediana de idade dos pacientes transplantados foi de 51 anos (20-75), 37 (53%) sexo masculino, 20% teve performance status > 1; 60% apresentaram sintomas B e 67% teve algum sintoma relacionado à doença. 73% apresentou estadio III/IV; 16% dos casos tinham envolvimento extranodal > 1 e 17% tinham doença com bulky; Os subtipos mais frequentes foram 39% Linfoma de células T periféricas não especificado; 28% Linfoma de grandes células T anaplásicas, ALK- e 17% Linfoma angioimunoblástico. O grupo TCTP-C teve 54 pacientes e o status da doença antes do procedimento foi 50 (92,5%) casos com RC e 4 RP (7,5%); o TCTP-S foi realizado em 18 casos e 2 pacientes foram transplantados em ambos os momentos. Em relação ao tipo de TCTP, na consolidação, foram realizados 48 autólogos e 6 alogênicos, enquanto no salvamento foram 13 autólogos e 5 alogênicos. Após uma mediana de seguimento de 23 meses (4-77) para o grupo TCTP-C e 25 meses (6-43) para TCTP-S, a SG do grupo com TCTP-C foi de 81% (IC 95% 69-93%) e 71% (IC 95% 24-88%) para o TCTP-S, P = 0.16; A SLP foi de 61% (IC 95% 45-77%) e 7% (IC 95% 0-19%), respectivamente, p < 0,0001. Analisando o grupo TCTP-S, a resposta após o TCTP foi 4 (22%) RC, 1 (5,5%) RP, 3 (16,5%) doença estável, 5 (28%) progressão e 5 (28%) morreram. A mediana de seguimento foi 10 meses (1-23), e a SG-S foi 54% e 56% SLP-S em dois anos. Conclusões: De acordo com os dados da literatura, o TCTP pode indicar um controle em longo prazo para o LCTP alcançando uma estabilização após 5 anos e nossos dados apresentam curvas de 3 anos para o grupo consolidação, sugerindo que este procedimento é uma boa opção para melhorar os resultados finais. (Número do Clinical trials: NCT03207789).

Introduction:Adult T cell Leukemia/Lymphoma (ATLL) is a mature T-Cell-neoplasm related to human T-cell lymphotropic virus type 1 (HTLV-1) infection that shows variable clinical presentation and adverse prognosis with shorter overall survival (OS) when compared to other peripheral T-cell lymphomas (PTCL). Previous epidemiological studies estimated cumulative incidence in endemic regions around the world. In Brazil, mainly due to its vast dimension, data collection has limitations and is subject to bias. In April 2015 theBrazilianT-cell longitudinal project initiative was launched. One of the primary purposes was the collection of epidemiological and clinical data from the most frequent subtypes of newly diagnosed PTCL. Among them, 41 cases of ATLL were recorded. Objectives:The aim of this study is to describe clinical features, frequency and overall survival (OS) of 41 cases of ATLL registered in the ongoingBrazilianT-Cell Project. Methods:This is an ambispective observational study design collecting baseline characteristics, clinical features including date of diagnosis, clinical subtypes, B symptoms, performance status, Ann-Arbor staging, HTLV-1 status, number of sites, nodal and extra nodal presentation and types of skin lesions, peripheral blood counts and biochemical tests, front-line treatment and best response after first-line treatment. REDcap Platform has been used to collect and store data and for descriptive analysis the IBM-SPSS version 24 was applied. Kaplan-Meier method estimated the OS, whereas Log-Rank tests to compare its curves. OS period was calculated from diagnosis date until death or last seen date, and event was death by any cause. Results:Out of 281 cases of PTCL registered so far, 41 were ATLL cases. The median age was 50 years (34-88), 25 (64%) female; a higher incidence of lymphoma subtype was observed (46%), followed by acute (29%), chronic (17%) and smoldering (8%). Most of the patients (85%) had advanced-stage disease (III-IV, Ann-Arbor) and 56% had B symptoms (Table 1); 73% received chemotherapy with anthracycline-based regimens (46.5% CHOEP; 33.5% CHOP; 20% others) whereas 17% were managed with immunotherapy and antiviral therapy. The overall response rate was 30%; no response or progression 46%; stable disease 9% and 15% no data available yet (Table 2). Median follow-up was 13 months and 25 months for 41% of alive patients. Two year OS was 39% (95%CI: 23-55%) (Figure 1). Smoldering and Chronic subtypes showed better OS when compared with acute and lymphoma (100% smoldering, 86% chronic; 30% lymphoma type and 13% acuteP=0.04) (Figure 2). The multivariate Cox Regression analysis found male gender (HR 10.9 95%CI: 3.0-39.7, P Discussion:ATLL prognosis remains poor regardless of the type of treatment regimen and may be associated with the high incidence of lymphoma and acute subtypes, as well as advanced stage disease presentation. Despite the high number of cases seen in southeastern region of Brazil, it is important to emphasize there are still limited data from other regions. Albeit the sample size is small, these findings confirmed literature review data so far, with poor overall survival in a short time and gender and albumin as predictors of OS in the multivariate analysis. Conclusion:This study highlights the poor prognosis associated with ATLL. Moreover, it seems relevant to expand this study to all Brazilian regions. Hence, the need for early diagnosis and new treatment strategies, able to reduce mortality is warranted, that could possibly change the nature and spectrum of disease. Disclosures Federico: Spectrum:Consultancy, Membership on an entity's Board of Directors or advisory committees;Sandoz:Consultancy, Membership on an entity's Board of Directors or advisory committees;Cephalon/Teva:Research Funding;Mundipharma s.r.l.:Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Millennium/Takeda:Research Funding;Roche:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda:Consultancy, Membership on an entity's Board of Directors or advisory committees.

The aim of this study was to determine factors that influence unsuccessful peripheral blood stem cell (PBSC) harvesting in patients with multiple myeloma (MM). Retrospective data of 186 MM patients who received G-CSF as mobilization were analyzed. Patients with successful harvest were compared with those who failed (using 2 definitions of failure2 and4 CD34 cells×10(6)/mm(3)). The groups were compared regarding age, gender, body weight, baseline platelet count, receipt of radiotherapy, number of prior chemotherapy regimens, PBSC count before collection, processed and collected volume, collect replace, number of sessions and final number of PBSC collected. By multivariate analysis, a baseline platelet count161,000 cells/mm(3) was associated with PBSC harvest lower than 2×10(6)/kg, and age58 years was related to PBSC harvest lower than 4×10(6)/kg CD34 cells/kg. Patients with these parameters should not receive mobilization protocols with G-CSF alone. Alternative protocols should be tested in this high risk harvest failure population.

Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social–economic profile.

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% or10% BCR-ABL(IS) levels) with different outcomes at 3 years regarding major molecular response (MMR, 91%, 47%, 22%, p0.001), failure-free survival (FFS), progression-free survival (PFS, 96%, 89% and 78%, p = 0.05) and overall survival (OS). After 6 months, patients with MR1% had higher 3-year MMR (83% vs. 16%, p0.001), FFS, PFS (94% vs. 84%, p = 0.05) and OS. Four patients had 3-month and 6-month MR10% and1%, respectively (3-year FFS 50%). Thirteen had 3-month and 6-month MR10% 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.

The diagnosis of strongyloidiasis relies upon the identification of the parasite in stool samples. In 1981, a serologic assay was developed, which was useful in the diagnosis of strongyloidiasis in the immunocompetent host. In the present study, we evaluated the enzyme-linked immunosorbent assay (ELISA) in patients with hematologic malignancies. Between April 1995 and December 1998, sera from 164 consecutive patients were tested for the presence of IgG antibody to Strongyloides stercoralis. Patient was considered uninfected after at least three negative stool examinations. The prevalence of strongyloidiasis was 13%. The underlying diseases were acute leukemia in 21% and lymphoma in 52% of the patients. The majority of the patients were receiving chemotherapy (93%) and steroids (76%). The sensitivity, specificity, and positive and negative predictive values were 68%, 89%, 48%, and 95%, respectively. The ELISA may be an excellent assay to rule out the diagnosis of strongyloidiasis in patients with hematologic malignancies.

Prolongation of bradykinin half-life following kininase inhibition has been proposed as the reason for the potentiation of kinin effects. We have reassessed this assumption by using three different isolated smooth muscle preparations and simultaneously studying the inhibition of kininase activity and the potentiation of bradykinin effects by enalaprilat and BPP9a. Rat duodenum displayed higher total kininase activity, metabolizing half of the added bradykinin in 6.5 min, while this time for rat uterus was greater than 60 min. Guinea-pig ileum showed the intermediate value of 14.6 min. Enalaprilat and BPP9a slowed the metabolism of bradykinin by 50–100% in rat duodenum and by 50–180% in guinea-pig ileum, showing that a significant fraction of total kininase activity appears to be due to kininase II. In rat duodenum, an almost complete blockade of kininase activity was achieved when bacitracin and mergetpa were used together with enalaprilat. Enalaprilat and BPP9a potentiated bradykinin effects in guinea-pig ileum and rat uterus. In contrast, bradykinin-induced relaxations and contractions in rat duodenum were not potentiated by enalaprilat, BPP9a, or by the enzyme inhibitor mixture (enalaprilat – bacitracin – mergetpa). The results suggest that inhibition of bradykinin enzymatic metabolism by kininases does not necessarily lead to the potentiation of bradykinin effects.Key words: bradykinin, kininase II, potentiation, smooth muscle.

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.

A total of 21 patients with hematologic malignancies were given thiabendazole for treatment of strongyloidiasis. Fifteen patients were cured. Since there were no relapses, it is unlikely that maintenance therapy has a role in the management of strongyloidiasis in this population of patients.

Introduction In patients with imatinib-resistant chronic myeloid leukemia (CML) treated with a second generation tyrosine kinase inhibitor (2GTKI), the initial molecular response at 3 months (3m-IMR) has been shown to be predictive of long-term outcomes. However, there is no consensus regarding the best cutoff for the BCR-ABL1 transcript levels, with 1% and 10% being proposed in different studies. Also, additional prognostic factors such as baseline tyrosine kinase (TK) mutations and a prognostic scoring system (PSS) (Jabbour, 2011) have been proposed. In this study, we addressed those issues in an homogeneous group of imatinib-resistant CML patients treated in a single center for a median follow-up of 36 months (14-60). Patients and Methods 134 patients with a diagnosis of CML treated either with dasatinib (N=64) or nilotinib (N=70) due to imatinib failure were included. Imatinib failure was defined as any of the following: no complete hematologic response at 3 months, no cytogenetic response at 6 months, no major cytogenetic response at 12 months, no complete cytogenetic response (CCR) at 18 months, or loss of hematologic or cytogenetic response at any time. Patients with the T315I mutation were excluded. Molecular analysis was performed in a properly standardized laboratory every 3 months from the beginning of the 2GTKI, and results are presented according to the international scale. The study's primary endpoint was the 3-year event-free survival (EFS) after 2GTKI. Secondary endpoints were the best response levels attained under 2GTKI (BMR). The factors analysed were the 3m-IMR, age, gender, Sokal and EUTOS scores at diagnosis, failure to achieve a complete cytogenetic response, TK mutations, PSS score and type of 2GTKI. A multivariate analysis with the factors significant at P Results There were 74 males and 60 females, with a median age of 46 years (4-79). The Sokal score was available in 93 patients: it was low in 25 (27%), intermediate in 24 (26%) and high in 44 patients (47%). The EUTOS score was low in 61 and high in 32 patients. The best cytogenetic response to imatinib was complete in 32 patients, major in 18, minor in 12, and minimal or no response in 72 patients. The 62 patients who attained at least a minor cytogenetic response lost it before starting the 2GTKI. TK mutations were present in 33 patients (105 tested). The PSS score was low-risk in 59 (44%), intermediate in 61 (46%) and high-risk in 14 (10%) patients. The 3m-IMR was < 1% in 59 (44%) patients, 1% to 10%, respectively. Conclusions BCR-ABL1 transcript levels at 3 months identified a good-risk group (BCR-ABL1< 1%) with 3y-EFS of 87%, an intermediate-risk group (BCR-ABL1 1% to Disclosures: Boquimpani: BMS: Consultancy; Novartis: Consultancy, Research Funding. Lobo:Novartis: Research Funding. Spector:Novartis: Honoraria, Research Funding.

Abstract 3422 Poster Board III-310 Autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL). The absolute lymphocyte count (ALC) in the autograft has been shown to correlate with survival after ASCT for lymphomas, but which lymphocyte subset in the autograft is responsible for this effect remains unknown. The aim of the present study was to retrospectively evaluate the impact of the number of CD4+ and CD8+T-cells in the autograft on the outcomes of ASCT. Patients with a diagnosis of relapsed HL or DLBCL submitted to an ASCT between 1999 and 2006 were included. Patients were excluded if a sample of the autograft was unavailable. No patient had HIV infection. The mobilization scheme consisted of subcutaneous G-CSF in 70% of the patients. The remaining patients were given cyclophosphamide 1.5 g/m2 or 4g/m2 with G-CSF. The conditioning regimen was cyclophosphamide 6 g/m2, BCNU 300 mg/m2 and etoposide 1200 mg/m2 in all but two patients. Growth-factor support was started five days after the infusion. The ALC in the autograft was calculated as the lymphogate in the FACS analysis. T-cell count was calculated as the total number of CD3+ lymphocytes, and T-cell subsets were determined by the number of CD4+ or CD8+ cells in the autograft. The antibodies used in the FACS analysis were: anti- CD45-FITC (BD- PharMingen), anti- CD4-FITC/ CD8-PE/ CD3-PercP (BD- PharMingen) and anti- CD3-FITC (BD- PharMingen). Among the 48 patients (34 with HL and 14 with DLBCL) available for study, the median age was 34 years (12-65), 37 were males (73%), and advanced stage disease (Ann Arbor stage III or IV) was present in 38 patients (75%). The number of previous treatments ranged from one to four, and radiotherapy had been given to 51% of the patients. The median time from diagnosis to the ASCT was 1.8 years (0.4 to 15.3). The median numbers of infused cells were mononuclear cells 5.7×108/kg (1-15), CD34+cells 4.1×106/kg (1.7-19.6) and lymphocytes 261/mm3 (23-978). The median numbers of T-cell subpopulations were CD3+ 164/mm3 (7-706), CD4+ 68/mm3 (3-284), CD8+ 75/mm3 (3-401), CD4-CD8- 9/mm3 (0.3-154) and CD4+CD8+ 1.3/mm3 (0.01-15). Those values were used as cutoffs for the lymphocyte count comparisons. In univariate analysis, the mobilization scheme including chemotherapy was associated with a higher median number of collected CD34+ cells/Kg (8.0 vs 4.17, p= 0.003), with a lower median number of total lymphocytes (203 vs 372, p=0.003), CD3+ T-cells (144 vs 249, p=0.005), CD8+ T-cells (50 vs 114, p The median follow-up of the living patients was 1.9 years from the ASCT. Survival curves could be determined for 46 patients: 27 were alive, and 19 patients had died at the time of this analysis. In the univariate analysis, the type of disease, ALC, CD3+, CD4+, CD8+ and CD4+CD8+ T-cells had a statistically significant association with the 2-year overall survival (OS). The best discriminator of survival was the number of CD4+ T-cells (95% vs 43%, p Multivariate analyses of OS and EFS were performed, including the type of disease and the counts of CD4+ and CD4+CD8+ T-cells. Regarding OS, only CD4+ T-cells (HR 11.87, 95%CI 2.71-51.99, p=0.001) and disease type (HR 2.54, 95%CI 1.00-6.45, p=0.05) remained statistically significant. Regarding EFS, only CD4+ T-cells (HR 2.94, 95%CI 1.28-6.79, p=0.01) and CD4+CD8+ T-cells (HR 2.88, 95%CI 1.18-7.04, p=0.02) retained statistical significance. If the findings in this study are confirmed, efforts should be made to collect sufficient numbers of CD4+ cells in every patient. A carefully designed prospective study is needed to address this issue, and to better define the various lymphocyte subpopulations involved in this phenomenon. Disclosures No relevant conflicts of interest to declare.

Abstract 1226 Poster Board I-248 Background The value of FDG-PET in mantle cell lymphoma (MCL) has not been addressed in a homogeneous group of pts. The optimal initial therapy is controversial; however, intensified therapy followed by consolidation with high-dose therapy and autologous stem cell rescue (HDT-ASCR) is associated with superior progression-free survival (PFS) compared to CHOP-based therapy. In this study, we examined the prognostic value of FDG-PET in a group of uniformly treated pts with upfront HDT-ASCR consolidation. The role of FDG-PET was evaluated: at baseline; as a predictor of proliferation index (PI); and as interim evaluation after induction therapy prior to HDT-ASCR. Pts and Methods Pts received sequential therapy consisting of sequential R-CHOP-14 × 4 followed by RICE x 2-3 cycles and consolidation with HDT-ASCR. FDG-PET and diagnostic CT imaging was obtained at baseline and after R-CHOP (N=75). The number of cycles of RICE was determined by the PET and CT response after induction with R-CHOP-14×4; pts with FDG-avid disease received a third cycle. Additional therapy was administered in 10 pts who had persistent FDG-avid disease after RICE with the objective of achieving the best response prior to the HDT-ASCR. Therapy included bortezomib in 7 cases and other treatment in 3 cases. The PI was determined by quantitative image analysis of Ki-67 stained slides (N=39). The median follow-up was 3.4 years. Results The median age was 59 years, 71% had bone marrow disease and 85% had stage 4 disease. According to the MIPI score, 50% had low-risk, 35% had intermediate-risk and 15% had high-risk disease. The baseline FDG-PET was positive in 71 pts (95%) and the median SUV was 5.5 (1.6-14). The baseline SUV was not prognostic after the stratification of the pts by the median SUV (PFS 81% vs 84% and overall survival (OS) 100% vs 74%, p=0.15). The median PI was 22% for the pts with an SUV below the median and 36% for the other group (P=0.03, Mann-Whitney). Interim FDG-PET evaluation after induction with R-CHOP-14 was available in 69 pts among the 71 with a positive test at baseline, the exam was negative in 49 pts (71%). A negative interim FDG-PET was associated with a better PFS (84% v 40% at 4years, p Conclusions In MCL, a baseline FDG-PET is useful as not all cases are positive. Though SUV correlates with the PI, the pretreatment SUV alone is not prognostic. Pts in PR by CT are separated by the FDG-PET result with negative pts having a superior outcome. The interim FDG-PET after induction with R-CHOP-14 × 4 is prognostic for PFS and OS in a program of sequential therapy with upfront consolidation with HDT/ASCR. Disclosures No relevant conflicts of interest to declare.

PKCβ is a regulatory factor involved in the nuclear factor kappa B pathway. PKCβ gene expression was pinpointed through microarray studies by Shipp et al as one of thirteen, among over six thousand studied genes, to be associated with the probability of cure in DLBCL. The authors also reported a good correlation between PKCβ gene expression and protein expression, and added that in their hands PKCβ protein expression was closely associated with the clinical outcome. Therefore, we analyzed the PKCβ protein expression in 71 samples of DLBCL (44 nodal) by immunocytochemistry. A case was considered positive only if the antigen was unequivocally expressed in the large cells. PKCβ expression was found in 10/71 (14%) of the cases. Some cases had PKCβ expression only in the small lymphocytes, and were considered negative, since this antibody intensely stained mantle zone cells. Most samples had positive internal controls, as both plasma cells and residual mantle zone cells were strongly stained by the antibody. The patients’ clinical and biological features were similar in PKCβ positive and negative cases (median age 51 vs. 58 years; male gender 50% vs. 67%; extranodal disease 30% vs. 39%; high IPI 10% vs. 27%; Bcl-2 expression 50% vs. 41%, and CD10 expression 20% vs. 23%). None of these differences were statistically significant. The presence of PKCβ expression was not related to 7-year overall survival (56% vs. 48%, p=0.8). The 5-year event free survival was 54% and 33% in PKCβ negative and positive cases, respectively (p=0,7). A complete remission after an anthracycline based first line chemotherapy was obtained in 75% and 90% of PKCβ negative and positive cases, respectively (p=0,4). However, the 5-year DFS was 80% and 37%, for PKCβ negative and positive cases, respectively (p

Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social-economic profile.