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The Hematology Service at the University Hospital of Federal University of Juiz de Fora (HU-UFJF)/Brazil carried out a research project focused on assessing the toxicity and effectiveness of progressive Lomustine doses in association with Etoposide and Cyclophosphamide in the Autologous Hematopoietic Stem Cell Transplantation (AHSCT) conditioning regimen adopted for lymphoma patients. During the follow-up, a 31-year-old woman belonging to the 400 mg/m2 Lomustine cohort evolved with neuromuscular complications 6 months after AHSCT. Initially, she experienced diffuse pain, mainly proximal weakness in the lower limbs; however, it got worse 10 days after vaccine protocol application. She evolved with rapidly ascending motor worsening, decreased ability to walk, foot paresthesia, binocular diplopia, areflexia, bulbar and dysautonomic symptoms such as sweating, tachycardia and postural hypotension. She experienced syncope episodes 72 h before being referred to intensive care unit at HU-UFJF.

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

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.

Introduction: Microvascular endothelial damage is a well-recognized complication of bone marrow transplantation (BMT) and the mechanisms of this disorder are still poorly under­stood. The objective of this scenario is to evaluate the relationship between inflammatory markers and other factors that influence platelet consumption and platelet transfusion yield, as well as the presence of embolic and / or vascular thrombotic events in patients submitted to high-dose chemotherapy conditioning for Bone marrow transplant. Material and Methods: Prospective analysis of patients, including 25 patients who under­went autologous and allogenic BMT. The patients were evaluated in relation to previous radiotherapy, CD34 + cell count, period of neutropenia, body mass index (BMI), ferritin, re­active C protein (RCP), relating these factors to the number of platelet transfusions, plate­let refractoriness and vascular events such as sinusoidal obstruction syndrome (SOS) and bone marrow grafting syndrome. Results: Only BMI> 25 Kg / m2 of the studied variables presented a statistically significant value (p = 0.003) in relation to the lower need for transfusion of platelet concentrate. For platelet refractoriness and / or vascular events none of the variables was statistically sig­nificant. The conditions found in the 3 cases of platelet refractoriness and in the 2 cases of vascular events have characteristics like those described in the literature. Conclusion: Although the cause is unclear, we agree with data reported in the literature that patients with high BMI have a lower need for transfusion of platelets. Small sampling limits our comparisons and significant statistical inference; however, we cannot rule out the relevance of a descriptive analysis of the results, especially if we consider that each patient should be evaluated in an individualized way in clinical practice.

Background The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

Aim The aim of this evidence implementation project was to improve the documentation of chemotherapy administration by nursing staff in a bone marrow transplant unit, to improve patient care and safety, as well as meet the legal and educational responsibilities of the nursing staff. Methods This evidence implementation project used the Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback framework for the design and development of an evidence-based audit and feedback change project. A baseline audit was conducted to assess current practices against best practice and identify areas requiring improvement. Next, the project team reflected on the results of the audit to develop and implement strategies for documentation improvement. Lastly, a follow-up audit was conducted to assess changes in practice improvement. Results The baseline audit results revealed practice areas requiring improvement; facilitators of and barriers to nursing documentation and practice improvement were identified. A checklist, educational session, Nursing Documentation Guidelines for Chemotherapy Administration, was implemented to improve nursing documentation. The follow-up audit demonstrated improved adherence across all audit criteria. Conclusion The checklist implemented for nursing documentation and education contributed to improved practices. To promote additional improvements, nurses will continue to utilize the tools developed and receive continued education through formal training and staff meetings. Future auditing is planned to ensure sustainability.

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The first HSCT program in Latin America started in 1979 at the Federal University Hospital (Curitiba, Paraná). Over the years, the number of centers performing transplants in the country increased, generating the need to know the results of this modality of treatment. Understanding the HSCT scenario in Brazil is still challenging since not all Brazilian centers report data to the Center for International Blood and Marrow Research (CIBMTR). Although it has been improving over the last years, infrastructure and trained data managers are still lacking. The partnership between the Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) and the CIBMTR, allowed the return of Brazilian data registered in the CIBMTR, through the Data Back to Center (DBtC), in a standardized and organized way. With this database it was possible to know the demographic data and the outcomes of transplants performed in Brazil. Between 2012 and 2021, complete information of 7,982 transplants were reported to the CIBMTR from 31 Brazilian transplant centers. The consolidation of the Hematopoietic Stem Cell Transplantation Brazilian Registry (HSCTBR) using CIBMTR infrastructure, allowed the Brazilian Summary slides development and update. Despite the difference in the number of cases and of follow-up time, the results in this study were similar to those presented in the US Summary Slides.

Patients with multiple myeloma (MM) in clinical con­ditions to be referred to autologous hematopoietic stem cell transplantation (AHSCT) generally start therapy with an induction chemotherapy followed by high-dose alkylating and AHSCT. The ideal regimen and the number of pre-AHSCT induction is still a controversial subject, however, opting for at least three to four cycles of chemotherapy including a drug with immunomodulatory action, a protea­some inhibitor, with a corticosteroid, are advised as the first line before AHSCT.

Patients undergoing hematopoietic stem cell transplantation (HSCT) usually experienced respiratory muscle weakness. Inspiratory muscle training (IMT) at HSCT has not been studied yet. Thus, it is important to evaluate the safety, feasibility, and preliminary effectiveness of IMT for hospitalized patients undergoing HSCT with an unstable and acute clinical condition. This is a randomized controlled feasibility study. Thirty-one hospitalized patients undergoing HSCT were randomized to the conventional physical rehabilitation (CON) or to the IMT group (conventional physical rehabilitation + IMT). IMT was carried out at 40% of maximal inspiratory pressure (MIP), 5 sessions weekly, 10–20 min/session. Primary outcomes were safety and feasibility (recruitment, adherence, and attrition rates) of IMT. Secondary outcomes were respiratory strength, respiratory rate, oxygen saturation, and frequency of patients with oxygen desaturation, bleeding, dyspnea, and acute pulmonary edema. Patients were allocated to the IMT (N = 15; 43.6 years) or to the CON group (N = 16; 46.6 years). The recruitment rate was 100%, the adherence rate was 91%, and attrition was 13% to IMT. Two events were observed in 126 IMT sessions (1.5%). MIP increased in the IMT group (P

Introdução: Os linfomas são um conjunto de neoplasias linfoides em que há o acúmulo de linfócitos malignos nos linfonodos, causando linfonodomegalia. Os linfomas são responsáveis por 3% a 4% dos cânceres no mundo. Estimativa mundial apontou 390 mil novos casos e 199 mil óbitos por linfoma não Hodgkin e 65 mil novos casos e 25 mil óbitos por Linfoma de Hodgkin no ano de 2012. Sendo a busca por cuidados terapêuticos e a tentativa de solucionar problemas de saúde conduzem indivíduo e familiares por caminhos compreendidos como itinerário terapêutico Objetivo: Conhecer o itinerário terapêutico de pacientes portadores de linfoma atendidos na rede pública por serviço de saúde especializado. Material e Métodos: Estudo prospectivo e descritivo com dados coletados em um hospital de referência em oncologia na Zona da Mata Mineira, no estado de Minas Gerais, Brasil. Resultados: Participaram do estudo 32 pacientes, sendo 18 do sexo masculino (56,3%), com idade entre 7 e 80 anos, caracterizados principalmente por baixos níveis de escolaridade e renda. Prevaleceu o linfoma não Hodgkin representado por 23 sujeitos (71,9%). Um total de 24 pacientes (75%) necessitou passar por três ou mais médicos até a obtenção do diagnóstico definitivo. O tempo médio entre o aparecimento dos sintomas e a realização do diagnóstico foi de 9,77 meses. A baixa renda dos pacientes contribuiu para a demora na busca ou obtenção do primeiro atendimento à saúde (p = 0,05) e consequente diagnóstico do linfoma. Conclusão: A dificuldade de acesso aos serviços de atenção à saúde e a baixa suspeita diagnóstica para a doença por parte dos profissionais possivelmente influenciaram o atraso no estabelecimento do diagnóstico.

Background OCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of B-lymphocyte differentiation by controlling expression of B-cell specific genes. BCL-2 gene is a potent inhibitor of apoptosis and it is essential during B-cell differentiation into germinal center. These genes may be expressed in diffuse large B-cell lymphoma (DLBCL), but the role of BCL-2 in its prognosis has been contradictory, and OCT-1 has yet to be tested. Methods In this study, we aimed to investigate the prognostic impact of OCT-1 and BCL-2 expression in DLBCL treated in the real world with immunochemotherapy in a single center. BCL-2 and OCT-1 genes were available in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR was isolated from formalin-fixed paraffin-embedded samples. The values obtained for gene expression were transformed in categorical variable according to their median. Results Cohort median age was 54.5 years (15–84), 49 (50%) were male, 38/77 (49.4%) and 40/77 (51.9%) presented OCT-1 and BCL-2 expression ≥ median, respectively. The overall response rate (ORR) in all patients was 68.4% (67/98), 65,3% (64/98) of patients acquired complete response, and 3.1% (3/98) partial response, while 6.1% (6/98) were primary refractory. The median follow-up was 3.77 years (95% CI: 3.2–4.1), with 5.43 (95% CI: 2.2-NR) of overall survival (OS) and 5.15 years (95% CI: 2.9-NA) of progression free survival (PFS). OCT-1 ≥ median was associated with shorter OS at univariate analysis (p = 0.013; [HR] 2.450, 95% CI: 1.21–4.96) and PFS (p = 0.019; [HR] 2.270, 95%CI: 1.14–4.51) and BCL-2 gene overexpression presented worse PFS (p = 0.043, [HR] 2.008, 95% CI: 1.02–3.95). At multivariate analysis, OCT-1 overexpression was associated with poor PFS (p = 0.035, [HR] 2.22, 95% CI: 1.06–4.67). Conclusion In this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.

Background: Diarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. Methods: The role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. Results: Thirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value = 0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value = 0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value = 0.06). Conclusions: The high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation. Keywords: Stem cell transplant, Diarrhea, Etiological agent, Coccidia

Patients with multiple myeloma (MM) have an increased risk for severe infections due to both the disease and anti-myeloma therapies. During the COVID-19 pandemic, case series of MM patients have demonstrated a poor outcome in those who required hospitalization due to COVID-19, and there are few data regarding those managed out of hospitals or risk factors for hospitalization. In Brazil, where the scenario is of restricted resources to treat MM patients and large numbers of COVID-19 cases and related death, the outcome can be even worse. Objective: To assess risk factors and outcomes of COVID-19 in Brazilian patients with MM. This retrospective case series investigated 81 MM patients with documented COVID-19, managed in and out-hospital, from 8 states, representing 4 of 5 regions in Brazil. This study has been conducted by "Grupo Brasileiro de Mieloma" (GBRAM), and the present analyses included cases from April 2020 to July 2021. Clinical features and risk factors were analyzed with the severity of COVID-19 and outcomes (hospital admissions, intensive care unit (ICU) admission, ventilatory support, and death). The frequency of MM treatment modification due to COVID-19 was also accessed. There were 81 MM patients (male 50%; median age 63 years; and ISS III at diagnosis 25%) diagnosed with COVID-19. At least one comorbidity was present in 47 (58%) patients: most frequently hypertension and diabetes (56% and 27%). Twenty-eight (35%) patients had more than one comorbidity. At COVID episode, 21 (26%) patients had an active disease or progression disease, and 40% received at least two prior lines of treatment. COVID-19 management required hospitalization in 49 (61%), ventilatory support in 30 (40%) and ICU in 28 (35%). Hospitalization was associated with age (p=0.008), presence of comorbidity (p=0.02), hypertension (p=0.02), presence of fever (p=0.005) and low respiratory symptoms (p=0.003). Ventilatory support was more frequent in patients with cardiac disease (p=0.05), receiving immunomodulatory (p=0.03), or monoclonal drugs (p=0.006). Patients receiving corticosteroids (p=0.02), immunomodulatory (p=0.06), or monoclonal drugs (p=0.06) in MM treatment had a higher frequency of ICU admission. By adjusted multivariate analysis, age, the clinical presentation with fever and low respiratory symptoms (p In this series, COVID-19 MM patients had a very high frequency of hospitalization, ventilatory support requirement, ICU admission, and deaths due to COVID-19. Although not associated with increased mortality, prior therapy drug classes were associated with severity of manifestation in our series. We also observed a high frequency of MM treatment delay in recovered patients, and the post-COVID clinical impact should be more explored. The high mortality observed reinforces the importance of preventing COVID-19, such as social distancing, wearing masks, and vaccination. Disclosures De Queiroz Crusoe: Janssen: Research Funding. Hungria: Takeda: Honoraria; Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel ; Abbvie: Honoraria; Sanofi: Honoraria, Other: Support for attending meetings/travel .

Objective: The success of autologus hematopoietic stem cell transplantation relies on CD34+ cells' availability in peripheral blood (PB), which is affected by several factors as age, sex, type of the disease, treatments, and others. In that regard, this prospective study aimed to evaluate the influence of these factors, correlating them with the pre-apheresis CD34+ cell count. Method: Before autologous hematopoietic stem cell transplantation, CD34+ cells were quantified in the pre-apheresis PB and the final product. Then, after the determination of minimum CD34+ value, clinical and laboratory parameters were compared between patients with higher and lower CD34+ cells count. Results: Out of the 34 patients, 29 presented more than 20,000 leukocytes/μl. Patients who failed in the mobilization presented

Objectives: To compare the severity of oral mucositis and the frequency of gastrointestinal mucositis, and to observe if there is impact of these adverse effects on overall survival (OS), in patients who underwent CBV (carmustine, BCNU, and VP-16) and LEAM (lomustine, etoposide, Ara-C, and melphalan) conditioning for autologous hematopoietic cell transplantation (aHCT). Method: We collected retrospective data from medical records (n = 120) of transplantation and mucositis in the digestive tract of Hodgkin’s and non-Hodgkin’s lymphoma patients. Results: The frequency of OM grade 1 was higher in LEAM (36.76%) than in CBV (19.72%, p=0.038). There were no significant differences between the frequency of gastrointestinal mucositis in the two regimens (CBV - 52.11% and LEAM - 63.27%, p=0.305). CBV regimen exhibited lower 1-year overall survival (OS) than did LEAM (p=0.003). Oral mucositis grade ≥2 was associated with reduced OS in the CBV group (p=0.013). CBV regimen (HR=2.98, p 0.005) and oral mucositis grade ≥2 (HR=2.17, p=0.013) interfered negatively on the OS rate. Conclusion: Oral mucositis was more severe in CBV than in LEAM, decreasing the OS rate. Further studies with comprehensive follow-up and toxicity analyses must be undertaken to clarify the safety of LEAM conditioning in the digestive tract.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy, representing 30-40% of all non-Hodgkin's lymphomas (NHLs). They comprise a group of aggressive and heterogeneous neoplasms in terms of clinical presentation, response to therapy and prognosis. The OCT-1 gene is a member of the homodomain-POU family of transcriptional regulators of B-lymphoid differentiation. OCT-1 acts by controlling the expression of specific B-cell genes, such as BCL-2, a potent inhibitor of apoptosis that is essential for the differentiation of B-cells in the germinal center. These genes can be expressed in DLBCL, but the role of BCL-2 in its prognosis has been contradictory and the prognostic impact of the OCT-1 gene has not yet been tested in this lymphoma. Methods: In this observational, retrospective, single-center study, we investigated the prognostic impact of BCL-2 and OCT-1 gene expression in Brazilian patients with DLCBL treated with immunopolychemotherapy R-CHOP in a real-world context. The BCL-2 and OCT-1 genes were assessed in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR (qRT-PCR) was isolated from formalin-fixed and paraffin-embedded (FFPE) samples. The values obtained for gene expression were transformed into categorical variables according to their medians (6.27 for BCL-2 and 24.5 for OCT-1). The association between clinical and laboratory variables and results of gene expression was verified by the Fischer test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate analysis was performed using Cox's bivariate regression method and multivariate analysis using Cox multiple regression methodology. Results: The median age of the cohort was 54.5 years (15-84), 50% (49/98) were male, 49.4% (38/77) and 51.4% (40/77) showed expression of OCT-1 and BCL- 2 ≥ median, respectively. The clinical characteristics of the 98 Brazilian patients with DLBCL that comprised our cohort are summarized in Table 1. The overall response rate (ORR) in all patients was 68.4% (67/98), 65.3% (64/98) showed a complete response (CR), and 3.1% (3/98) showed partial response (PR), while 6.1% (6/98) were primary refractory. With a median follow-up of 3.77 years (95% CI: 3.2-4.1), the median overall survival (OS) was 5.43 years (95% CI: 2.2-NR) and the median progression-free survival (PFS) was 5.15 years (95% CI: 2.9-NR). The 5-year OS and PFS was 54.2% (42.2% -64.8%) and 52.0% (40.1-62.6%), respectively. In the univariate analysis OCT-1 ≥ median was associated with shortened OS (HR: 2.45, 95% CI: 1.21-4.96, p = 0.013) and PFS (HR: 2.27, 95% CI: 1.14-4.51, p = 0.019). Overexpression of BCL-2 was associated with worse PFS (HR: 2.00, 95% CI: 1.02-3.95, p = 0.043). Subgroup analysis showed that OCT-1 overexpression predominated in elderly individuals (≥ 60 years) in a statistically significant mode (29/38 cases - 76.3%, p = 0.029). It was also observed that overexpression of OCT-1 was associated with worse OS in the high-risk adjusted International Prognostic Index (aIPI) subgroup (p = 0.048) - Figure 1, and worse PFS in patients ≥ 60 years old (p = 0.025) - Figure 2. In the multivariate analysis, overexpression of OCT-1 was associated with poor PFS (HR: 2.22, 95% CI: 1.06-4.76, p = 0.035). Conclusion: In this study, we demonstrated that overexpression of the OCT-1 gene was an independent prognostic factor associated with adverse outcomes in Brazilian patients with DLCBL. We also show that in patients with unfavorable risk, such as the elderly and those with intermediate-high and high-risk IPI, overexpression of OCT-1 contributed to the identification of a very high-risk clinical-molecular subgroup, where the results with standard R-CHOP therapy are unsatisfactory, and they may benefit from intensified therapeutic strategies. Our results are preliminary and need to be validated in subsequent studies of prospective nature and with an expanded sample. Disclosures No relevant conflicts of interest to declare.

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.

Introduction Several factors may interfere with the response to hematopoietic stem cell transplantation (HSCT) in myelodysplastic syndrome (MDS). Objective To evaluate the effect of cell source and type of conditioning on HSCT outcome in MDS. Methods We analyzed data from 258 MDS patients from the Latin American transplant registry in Brazil and Uruguay from 1988 to 2019. The statistics were performed on SPSS v.23.1, considering significant p Results A predominance of males (56.2%) and Caucasian individuals (84.5%) was observed. The most frequent age group was 51 to 60 years (2 -79 years) (26%). When stratified according to the Prognosis Scoring System (IPSS-R), 0.78% were classified as very low risk, 11.2% as low risk, 24% as intermediate risk, 21.3% as high risk and 4.7% as very high risk. A total of 38% of patients could not be classified according to the IPSS-R due to lack of data, such as cytogenetics. In myeloablative conditioning (MAC) (78.7%) the regimens were (bulssulfan/fludarabine, bulssulfan/cyclophosphamide, with or without total body irradiation (ICT)). Reduced intensity (RIC) (15.9%) was (bulssulfan/fludarabine, bulssulfan/cyclosphosphamide at reduced doses, with or without ICT and FluMel). The cell source was bone marrow (BM) (52.7%), peripheral blood (PB) (45.3%) and cord blood (2%). Major post-HSCT complications included acute (37.2%) and chronic (28.7%) graft versus host disease (GVHD). Regarding the possible predictors of acute, chronic GvHD and death, there was an association between type of cell source and the death outcome (p = 0.0336). Moreover, there was a significant association between acute GvHD and conditioning regimen (p = 0.0127) and cell source (p = 0.0004). There was also an association of chronic GvHD with the conditioning regimen (p Conclusion The results demonstrate the impact of conditioning and cell source on the HSCT outcome and reinforce the need for an appropriate assessment for better conduction results optimization.

Background: Patients undergoing hematopoietic stem cell transplantation (HSCT) usually experienced respiratory muscle weakness. The inspiratory muscle training (IMT) at HSCT has not been studied yet. Objective: To evaluate the safety, feasibility and preliminary effectiveness of the IMT for hospitalized patients undergoing HSCT. Methods: This is a randomized controlled feasibility study. Patients hospitalized for HSCT were allocated to a control group (conventional therapy) or to a IMT group (IMT + conventional therapy). The IMT was carried out at 40% of maximal inspiratory pressure (MIP), 5 sessions weekly, 10-20 min/session. The primary outcomes were safety and feasibility (recruitment, adherence and attrition rates) of IMT. Respiratory strength, respiratory rate and oxygen saturation were evaluated at admission and hospital discharge. Symptoms related to the respiratory system (oxygen therapy, bleeding, dyspnea and acute pulmonary edema) were also evaluated. Results: Patients were allocated to a IMT group (N=15; 43.6 yr) or to a control group (N=16; 46.6 yr). The recruitment rate was 100%, the adherence rate to IMT was 91% and attrition was 20%. It was observed 2 events (vomiting; oxygen desaturation) in 126 sessions (1.5%). MIP increased in the IMT group (P Conclusions: The IMT is safe, feasible and improves the inspiratory muscle strength.

Background: Patients undergoing hematopoietic stem cell transplantation (HSCT) have to worsen of functional capacity during hospitalization. However, it is not known whether the respiratory muscle strength is related to functional capacity. Objective: We hypothesized that functional capacity change is correlated to respiratory muscle strength changes in patients during hospitalization for HSCT. Methods: This is a prospective, observational study. Thirty one patients (18 males; 45 years) hospitalized for HSCT were eligible for this study. Respiratory muscle strength (Maximal Inspiratory Pressure - MIP and Maximal Expiratory Pressure - MEP; MVD300 Globalmed®) and functional capacity (6-Minute Step Test – 6MST) were assessed at admission (before HSCT) and hospital discharge (after HSCT). The delta values (discharge minus admission hospital) were subjected to a simple linear regression (P Results: Patients were submitted to autologous (94%) or allogeneic (6%) HSCT and the majority have diagnosis of Hodgkin´s (22%) or Non-Hodgkin´s Lymphoma (19%) or Multiple Myeloma (48%). As expected, MIP (Δ MIP = 4,5 cmH2O; CI95% = -2,6 – 11,7 cmH2O) and MEP (Δ MEP = -3,9 cmH2O; CI95% = -11,0 – 3,0 cmH2O) were related to 6MST (Δ 6MST = -2,8 cmH2O; CI95% = -13,2 – 7,4 cmH2O) (MIP vs. 6MST: P=0.03, R=0.39; MEP vs. 6MST: P=0.02, R=0.41). Conclusions: The modifications observed in the functional capacity are related to the respiratory muscle strength changes in hospitalized patients undergoing HSCT.

Background: Patients undergoing hematopoietic stem cell transplantation (HSCT) have muscle weakness, as well as exhibit reduced cardiorespiratory fitness, which can add to dyspnea. Objectives: To evaluate whether the dyspnea is related to functional capacity and skeletal muscle strength in patients prior to HSCT. In addition, we hypothesize that physical variables were lower than normative values. Methods: Patients hospitalized for autologous HSCT were assessed at hospital admission in terms of dyspnea (mMRC), peripheral muscle strength of upper (Handgrip Test) and lower limbs (Sit-to-Stand Test - time to 10th repetition), respiratory muscle strength (manovacuometry; MIP and MEP) and functional capacity (6-Minute Step Test). Dyspnea and physical variables were subjected to a simple linear regression. Moreover, the performed physical variables were compared to the normative values (Student´s t-test). Results: Twenty-nine patients were included (16 males; 46 yr). Dyspnea was related to functional capacity (R=-0.50; P Conclusions: Dyspnea was related to functional capacity and inspiratory muscle strength. Moreover, functional capacity and peripheral muscle strength are impaired in patients prior to autologous HSCT.

It has been suggested that bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) can be valuable in the treatment of patients with myelodysplastic syndromes (MDS). However, the influence of this approach on HSCT outcomes remains poorly defined. Therefore, our objective was to investigate the influence of treatment before HSCT in patients with MDS. We retrospectively analyzed data from the Latin American registry of 258 patients from 17 Latin American centers who underwent HSCT from 1988 to 2019. Our data showed that there was pre-HSCT. We detected no significant difference regarding the impact on overall survival of treated and untreated patients before HSCT. Despite these data, the type of previous treatment among treated patients showed a significant difference in overall survival. Treatment with hypomethylating agents together with pre-HSCT chemotherapy seems to result in better survival of the studied population. These data correspond to the first results obtained through cooperative work between various centers in Latin America comparing the different approaches to patients and reflecting their reality and challenges. Therefore, the selection of pretransplant bridge therapy should be analyzed and focus given primarily to those approaches that result in better survival of patients with MDS.

The aim of the study was to compare the quality of life (QOL) of patients undergoing hematopoietic stem cell transplantation who improved their functional capacity during hospitalization (increased functional capacity group) with that of patients who maintained or decreased functional capacity during hospitalization (decreased functional capacity group).This observational, longitudinal study included 27 hospitalized patients undergoing hematopoietic stem cell transplantation. Patients were divided into increased functional capacity group (16 patients) and decreased functional capacity group (11 patients). Functional capacity (6-min step test), peripheral muscle strength (sit-to-stand test and handgrip strength), and QOL (European Organization for Research and Treatment of Cancer) were assessed at admission and at hospital discharge.Increased functional capacity patients had increased functional capacity and peripheral muscle strength of the lower and upper limbs at hospital discharge (P0.01,0.01, and 0.02, respectively). The patients in the increased functional capacity group demonstrated an increase in global health and reduced symptoms at discharge (P = 0.02 and 0.03, respectively). No significant differences were observed between groups in the functional domain.Patients undergoing hematopoietic stem cell transplantation, who have improved functional capacity at discharge, also experience an improved QOL, with no such improvement noted among patients who have stable or reduced functional capacity. We recommend that the treatment protocol for hospitalized patients undergoing hematopoietic stem cell transplantation include an exercise program aimed at improving functional capacity.

Background The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30–100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. Methods A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. Results Fourteen (6.1%) patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3%) were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection ( p -value = 0.002). There were no significant differences for the other variables analyzed. Conclusion The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

Supplemental Digital Content is available in the text., Objective The aim of this study was to analyze the prognostic value of the interim PET (iPET)-computed tomography (CT) (iPET-CT) after two cycles of immunochemotherapy with the R-CHOP protocol in patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) treated with a curative intent in combination with the neoplastic cell origin defined by Hans’s immunohistochemstry algorithm followed in a reference center for cancer treatment in Brazil. Materials and methods We prospectively evaluated 147 DLBCL patients treated with R-CHOP-21 to assess the value of the International Prognostic Index, iPET-CT, and cell of origin by immunohistochemistry as prognostic markers in the rituximab era. Fluorine-18 fluorodeoxyglucose PET-CT was performed after two cycles (iPET-CT) and at the end of treatment in 111 patients. Lymphoma cases were categorized into germinal center (GC) and nongerminal center subtypes by immunohistochemistry according to Hans’s algorithm. Results The median age of GC-DLBCL patients (52.7 years) was lower than that of nongerminal center-DLBCL patients (59.4 years) (P=0.021); in addition, it was lower in patients with negative iPET-CT findings (52.7 years) versus positive findings (59.4 years) (P=0.031). The overall survival at 48 months was 100% for iPET-CT-negative GC-DLBCL patients and 61.2% for iPET-CT-positive GC-DLBCL patients (P=0.002). Progression-free survival at 30 months was 100% for iPET-CT-negative GC-DLBCL patients and 60.3% for iPET-CT-positive GC-DLBCL patients (P=0.001). Conclusion We conclude that iPET-CT associated with cell origin identified a very good prognostic group in DLBCL patients treated with R-CHOP. Video Abstract: http://links.lww.com/NMC/A59

Introduction: An epidemiological database is an important tool to characterize the population disease distribution, long-term effects of the diseases, impact of evolving treatments, to identify adverse events (AE) and their possible mitigation and to improve the healthcare system. Another important reason to create a database is to rapidly identify, recruit and enroll individuals for research activities. Based on these, the Brazilian Multiple Myeloma Study Group (GBRAM) developed an electronic database platform with the intention of prospectively registering the MM cases diagnosed at Brazilian healthcare services. Methods: This is a prospective, multicenter, open, epidemiological study, based on an electronic system register. Patients diagnosed with MM after January 1, 2018 have been included. The eligibility criteria were: intent-to-treat (ITT) MM patients, aged over 18 years and under care in any healthcare system (private, public and academic). All clinical and laboratory data, prognostic profiling, treatment patterns and responses, AE and survival were compiled. The data were analyzed with the NCSS® 2020 software. This project is registered in the Brazilian study platform control (Plataforma Brasil) linked to federal health authorities by the number CAAE-05340918.3.1001.8098. Results: To date, 1,113 patients at 44 reference centers were included. The median age was 64 (25 -96) years and 578 (52%) were male. According to the ECOG performance status: 0 = 185 (16.5%), 1 = 257 (23.2%), 2 = 144 (13%), 3 = 105 (9.5%), 4 = 62 (5.5%) and the not available data (NA) = 359 (32.3%). The ISS 1, 2, and 3 were 219 (19.7%), 286 (25.7%) and 406 (36.5%), respectively, the NA being 202 (18.1%). MM isotypes were 524 (47.1%) IgG, 202 (18.2%) IgA, 192 (17.2%) free-light chain, 4 (0.5%) IgM, 7 (0.8%) biclonal, 9 (0.7%) non-secretor and 175 (15.5%) NA. Regarding the treatment backbone, 427 (38.4%) patients received immunomodulators (IMID- thalidomide), 277 (20.4%), proteasome inhibitors (PI-bortezomib), 84 (7.6%), the combination of PI + IMID, 72 (6.6%), combinations with anti-CD38 monoclonal antibody (Daratumumab) and 253 (27%), other treatments. Based on the ITT analysis of 1003 cases, 636 (63.4%) patients were planned for bone marrow transplantation (BMT) and 367 (36.6%) were ineligible. After a median follow-up of 14.0 months, 150 (23.6%) of the planned patients had undergone the procedure, 284 (44.7%) had not yet been submitted and 202 (31.7%) had NA data. The overall survival (OS) was 80.9% for the total group at 20 months, 73.5% for ineligible and 95.5% for eligible. There was a significant improvement in eligible patients who had performed BMT, as compared to those who had not, HR 0.15 (0.09 - 0.26), p < 0.0001. A total of 142 deaths (12.8%) occurred, 51 (36%) of them being during the first 180 days. Discussion: Due to the lack of a reliable national register and the undoubtable need for a better understanding of MM for the development of public health and patient support measures, GBRAM has developed and built an electronic platform. This epidemiological study prospectively enrolled patients diagnosed since January 2018 and is of a nationwide scope. To date, 1,113 new cases were included. Despite the short follow-up, this analysis has identified differences in survival, comparing ISS stratifications and whether a BMT was performed or not. Conclusion: This project demonstrates the feasibility and importance of electronic platforms in the compilation of MM populational data for a better understanding of the clinical characteristics, treatment patterns and outcomes in the real world, permitting a clearer perception of local issues and thus, addressing possible improvement in public healthcare policy, such as the improvement of BMT access. Disclosures De Queiroz Crusoe: Janssen: Research Funding. Aranha:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ache Pharmaceutics: Honoraria.

Internal tandem duplications (ITD) of FLT3 gene occur in about a third of acute promyelocytic leukemias (APL). We investigated the patterns of blood count, surface antigen, expression, chromosome aberrations, PML–RARa isoform, gene expression profile (GEP) and survival in 34 APL patients according to FLT3–ITD status. 97% had a t (15;17) and all of them carried PML–RARa gene fusion, 8 (23.5%) had a FLT3–ITD mutation. Presence of ITD was associated with higher Hb and WBC levels, bcr3 isoform, CD34 expression, CD2 or CD2/CD34 expression. In a multivariate analysis, Hb > 9.6 g/dL and WBC ≥ 20 × 10 9 /L were important factors for predicting ITD presence. GEP showed that FLT3–ITD carriers clustered separately, even when as few as 5 genes were considered. This study provides further evidence that FLT3–ITDs carriers constitute a biologically distinct group of APL patients.

The aim of this study was to analyze the influence of dietary supplementation with whey protein concentrate (WPC) in the incidence of oral mucositis (OM) in patients undergoing hematopoietic stem cell transplantation (HSCT).Patients were supplemented with a daily intake of WPC delivering 50% of the daily protein requirements (DPR) according to the Dietary Reference Intakes and classified later based on the amount of ingested supplement until OM median onset.We evaluated 73 patients. Forty-three were part of the historical control and 30 were supplemented with WPC. The OM had a mean duration of 5.3 d (SD 4.5), ranging from the day of the infusion of stem cells until the 17th day after infusion and a median of 5 d after infusion. OM duration was influenced by the conditioning protocol (P 0.01) and WPC (P = 0.01). Patients who consumed the WPC in an amount ≥40% of DPR had a 35% reduction in duration of OM, and the incidence of OM grades 3 and 4 was 11 times smaller. Body mass index, serum albumin, and adverse reactions, such as diarrhea, nausea and vomiting, dysphagia, dry mouth and drooling, showed no statistically significant differences.WPC intake ≥40% of DPR helped to reduce the severity and duration of OM. The use of WPC in patients undergoing HSCT was shown to be safe, encouraging new studies in this population to assess its action mechanism.

Azidothymidine (AZT) is an antiretroviral drug that affects cell proliferation, apoptosis, and the NF-κB pathway. As multiple myeloma (MM) presents with constitutive activation of NF-κB, we analyzed the effect of AZT on human MM cell lines. We evaluated the cytotoxic effect of AZT in human MM cell lines sensitive (8226/S) or resistant to doxorubicin (8226/DX5) and human T cell lymphoblast-like cells, uterine sarcoma cells, and HUVEC using MTT assay. Cytotoxicity was also evaluated in vivo in nude mice xenografted with 8226/S tumor. The effect of AZT on the expression of genes involved in cell proliferation, apoptosis, angiogenesis, and the NF-κB pathway was analyzed in the xenografts using real-time polymerase chain reaction. AZT was effective against both 8226/S and 8226/DX5 cells in a dose and time-dependent manner (p = 0.02) in vitro and promoted cell cycle arrest in S phase in these cells. The tumor volume was lower in mice treated with AZT compared to untreated mice (p = 0.0003). AZT down-regulated the pro-proliferative genes encoding AKT1, MYC, STAT1, MAPK8, MAPK9, CCL-3, Bcl-3, and cyclin D2; pro-angiogenenic genes encoding VEGF and IL8; and genes involved in cell adhesion (ICAM1 and FN1) and the NF-κB pathway. AZT up-regulated the expression of tumor suppressor gene FOXP1 and the pro-apoptotic genes encoding BID, Bcl-10, and caspase-8. Thus, we demonstrated the cytotoxic effect of AZT in human MM cell lines for the first time. Our data may provide the rationale for future clinical trials of AZT for treating MM.

CONTEXT AND OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) has been widely used for treating oncological and hematological diseases. Although HSCT has helped to improve patient survival, the risk of developing infection during hospitalization is an important cause of morbidity and mortality. This study aimed to analyze the infection profile during hospitalization and the associated risk factors among patients undergoing autologous HSCT at the University Hospital, Universidade Federal de Juiz de Fora. DESIGN AND SETTING: This was a cross-sectional study on patients undergoing autologous HSCT at a public university hospital. METHODS: Patients with febrile neutropenia between 2004 and 2009 were retrospectively evaluated regarding their infection profile and associated risk factors. RESULTS: Infection occurred in 57.2% of 112 patients with febrile neutropenia. The main source of infection was the central venous catheter (25.9%). Infection was chiefly due to Gram-positive bacteria, although Gram-negative-related infections were more severe and caused a higher death rate. Sex, age, skin color, nutritional status and underlying disease were not associated with the development of infection. Patients with severe mucositis (Grades III and IV) had a higher infection rate (P < 0.001). Patients who developed pulmonary complications during hospitalization had higher infection rates (P = 0.002). Infection was the main cause of death (57.1%) in the study sample. CONCLUSION: Strategies aimed at reducing infection-related mortality rates among patients undergoing autologous HSCT are necessary. CONTEXTO E OBJETIVO: O transplante de células-tronco hematopoiéticas (TCTH) vem sendo amplamente utilizado no tratamento das doenças onco-hematológicas. Embora o TCTH tenha colaborado para a melhora na sobrevida dos pacientes, o risco de desenvolver infecção no período de internação é uma importante causa de morbi-mortalidade. O presente estudo teve como objetivo analisar o perfil das infecções no período de internação e os fatores de risco associados entre os pacientes submetidos ao TCTH autólogo, no Hospital Universitário da Universidade Federal de Juiz de Fora. TIPO DE ESTUDO E LOCAL: Trata-se de um estudo transversal sobre pacientes submetidos a transplante autólogo, em um hospital público universitário. MÉTODOS: Foram analisados retrospectivamente os pacientes que apresentaram neutropenia febril no período de 2004 a 2009, com relação ao perfil infeccioso e os fatores de risco associados. RESULTADOS: A infecção foi determinada em 57,2% dos 112 pacientes com neutropenia febril. A principal fonte de infecção foi o cateter venoso central (25,9%). A infecção ocorreu principalmente devido a bactérias Gram-positivas, apesar de as infecções causadas por bactérias Gram-negativas terem sido mais graves e causado maior taxa de morte. Sexo, idade, cor da pele, estado nutricional e doença de base não estiveram associados com o desenvolvimento da infecção. Pacientes com mucosite grave (graus III e IV) apresentaram maior taxa de infecção (P < 0.001). Os pacientes que desenvolveram complicações pulmonares durante a internação apresentaram maiores taxas de infecção (P = 0,002). A infecção foi a principal causa do óbito (57,1%) na amostra estudada. CONCLUSÃO: São necessárias estratégias voltadas para a redução da taxa de mortalidade relacionada com infecção entre pacientes submetidos ao TCTH autólogo.