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The treatment and evolution of B-cell non-Hodgkin lymphoma (B-NHL) has undergone important changes in the last years with the emergence of targeted therapies, such as monoclonal antibodies, small molecules, antibody-drug conjugates, and bispecific antibodies. Nevertheless, a significant portion of patients remains refractory or relapsed (R/R) to the new therapeutic modalities, representing thus an unmet medical need. The use of CAR-T cells for the treatment of B-NHL patients has shown to be a promising therapy with impressive results in patients with R/R disease. The expectations are as high as the imminent approval of CAR-T cell therapy in Brazil, which it is expected to impact the prognosis of R/R B-NHL. The aim of this manuscript is to offer a consensus of specialists in the field of onco-hematology and cellular therapy, working in Brazil and United States, in order to discuss and offer recommendations in the present setting of the use of CAR-T cells for patients with B-NHL.

Allogeneic stem cell transplantation (HSCT) remains a potentially curative approach for acute lymphoblastic leukemia (ALL), especially for high-risk patients and those with relapsed/refractory disease, although its efficacy is offset by a not-negligible toxicity. Adult patients with ALL fare worse in developing countries, with little data about the HSCT in this setting. In this study, we aimed to describe outcomes and examine risk factors for overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and graft-versus-host disease (GVHD) after HSCT for ALL in Brazilian centers. This retrospective registry study included patients with ALL or ambiguous lineage leukemia age16 years who underwent a first HSCT at 5 Brazilian centers between January 2007 and December 2017. A total of 275 patients were included, with a median age of 31 years (range, 16 to 65 years). Thirty-five percent were Philadelphia chromosome-positive. A matched sibling donor was used in 53%, a matched unrelated donor (MUD) in 19%, a mismatched unrelated donor in 9%, a haploidentical donor in 19%, and umbilical cord blood in 5%. The engraftment failure rate was 1.5%. The 5-year cumulative incidence of acute grade II-IV was 54.2%, and that of chronic GVHD was 26.2%. Five-year CIR and NRM were 28.1% and 34.1%, respectively. Central nervous system involvement at diagnosis (hazard ratio [HR], 2.2) and disease status (HR, 1.8 for second or later complete response and 7.9 for refractory) were associated with increased relapse incidence, whereas the use of peripheral blood graft (HR, .51) and a haploidentical donor (HR, .4) significantly decreased relapse incidence. Five-year OS and LFS were 40.7% (95% confidence interval [CI], 35.1-47.1) and 37.8% (95% CI, 32.3-44.1), respectively. Patient age, donor age, and disease status were independently associated with OS and LFS. Pre-HSCT positivity of minimal residual disease (.01%) was associated with worse LFS (HR, 1.47) in available cases. This is the largest series of adults with ALL undergoing HSCT from Brazil reported to date. Although OS and LFS were similar to data reported in the literature, NRM was higher. Patient age and donor age outweighed donor type or graft source in our analysis. Interestingly, haploidentical HSCT was associated with lower CIR, whereas the use of MUDs was associated with higher NRM and GVHD rates. These results impact donor selection strategy in Brazil with the aim of offering timely HSCT for high-risk ALL patients in our setting.

The advent of newer second-line medical therapies (SLMT) for immune thrombocytopenia (ITP) has contributed to decreased rates of splenectomy, following a trend to avoid or delay surgery. We aimed to characterize the long-term outcomes of laparoscopic splenectomy (LS) for ITP at our institution, examining differences in LS efficiency when performed before or after SLMTs. Adults with primary ITP who underwent LS between 2002 and 2016 were identified. Retrospective review of electronic medical records was supplemented with telephone interviews. Treatment response was defined according to current guidelines as complete responders (CR), responders (R), and non-responders (NR). Kaplan–Meier estimates assessed relapse-free rates, and predictors of long-term response were investigated using logistic regression. 109 patients met inclusion criteria, from which 42% were treated with an SLMT before referral to LS. LS was completed in all cases, with no conversions or intraoperative complications. The perioperative morbidity was 7.3%, including 3 deep vein and 2 portal vein thrombosis, one reoperation for bleeding, and no mortalities. Splenectomy was initially effective in 99 patients (CR + R = 90.8%), and 10 patients were NR. At a median 62-month follow-up, 25 patients relapsed, resulting in a 68% CR + R rate. Proportion of CR + R was similar in patients who previously received SLMT and those who did not (61 vs. 76.7%, p = 0.08). CR + R patients were younger (45 vs. 53, p = 0.03), had higher preoperative platelet counts (36 vs. 19, p = 0.01), and experienced a higher increment in platelet counts during hospital stay (117 vs. 38, p

Introduction: Allogeneic stem-cell transplantation (HSCT) remains a potentially curative approach for acute lymphoblastic leukemia (ALL), especially for high-risk patients and those with relapsed/refractory disease, although its efficacy is offset by a not negligible toxicity. Adult patients with ALL fare worse in developing countries with low data about the HSCT in this setting. In this study, we aim to describe outcomes and examine risk factors for overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and graft-versus-host disease (GVHD) after HSCT for ALL in Brazilian centers. Methods: This is a retrospective registry study. Patients with ALL or ambiguous lineage leukemia above 16 years who underwent a first HSCT in 5 Brazilian centers between January 2007 and December 2017 were included. Kaplan-Meier method and competing risk analysis were used. Multivariable analysis (MVA) was performed using Cox regression and the Akaike's information criteria was used for model selection. Cut-offs for continuous variables were calculated through "findcut" R function. Center effect was evaluated by using frailty model. Results: Overall, 275 patients were included with a median age of 31y (range, 16-65). Philadelphia chromosome was found in 35%. Baseline characteristics are summarized in Table 1. Matched sibling donor (MSD), matched unrelated donor (MUD), mismatched unrelated donor (MMUD), haploidentical donor and umbilical cord were reported in 53%, 19%, 9%, 19%, and 5%, respectively. Total body irradiation (TBI) was used in 67% of myeloablative HSCT. Median time to HSCT in CR1 was 7.8 months. Engraftment failure rate was 1.5%. Median follow-up time was 6.4 y. Cumulative incidence of acute grade II-IV and chronic GVHD were 54.2% and 26.2%, respectively. In MVA, the use of MUD (HR=2.3) and increased donor age (HR=1.02) were associated with GVHD. Five-year CIR was 28.1% (95% CI 22.9-33.6) and 5-y NRM was 34.1% (95% CI 28.4-39.8). At D+100, NRM incidence was 22.6%. Central nervous system involvement at the diagnosis (HR=2.2), and disease status (HR 1.8 for CR2+, and HR 7.9 for refractory) increased relapse incidence, whereas the use of peripheral blood graft (HR=0.51) and haploidentical donor (HR=0.4) significantly decreased relapse incidence. In MVA, NRM was increased by patient's age (HR=1.04), refractory status (HR=4.2), MUD (HR=3.8) and donor age (HR=1.02). Center effect was significantly associated with relapse and NRM. Five-year OS and DFS were 40.7% (95% CI 35.1-47.1) and 37.8% (95% CI-32.3-44.1), respectively (Figure 1). Patient's age, donor age and disease status were independently associated with OS and DFS (Table 2). When GVHD (as a time-dependent variable) was introduced in the MVA for OS and DFS, it was associated with decreased OS (HR 4.2, p0.01%) was associated with worse DFS in univariate analysis (HR=1.47) in available cases. Conclusions: This is the largest series of ALL adults receiving HSCT from Brazil. While OS and DFS were similar to published data, NRM was higher. Patient's age and donor age outweighed donor type or graft source in our analysis. Interestingly, haploidentical HSCT related to lower CIR, whereas the use of MUD was associated with higher NRM and GVHD rates. These results impact on donor selection strategy in our country, aiming to timely offer HSCT for high-risk ALL patients in our setting. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction. COVID-19 pandemic has spread worldwide and reached HSCT centers in many countries. The first proven case of COVID-19 in Brazil was diagnosed in São Paulo by the end of February 2020. The Brazilian Society of Marrow Transplantation (SBTMO) promptly published local recommendations for the diagnosis and management of COVID-19 in HSCT centers. We describe the main clinical findings and outcomes of SARS CoV-2 infection and COVID-19 in 22 HSCT recipients from two Brazilian HSCT centers, followed up for at least 14 days. Methods. The detection of SARS CoV-2 infection was performed by RT-PCR in all transplant candidates before admission, and in all HSCT recipients with respiratory symptoms. Other respiratory viruses were also investigated by direct fluorescent assay (DFA) or RT-PCR. COVID-19 was managed according to the SBTMO recommendations. Results. From March to June 2020, SARS CoV-2 infection was detected in 5 asymptomatic patients (29.4%) and COVID-19 was diagnosed in 17 HSCT recipients with respiratory symptoms (7 AUTO, 6 MRD, 5 MUD and 4 HAPLO) at a median of 94 days after HSCT (range -6 to +1,850). The asymptomatic cases at diagnosis remained so during follow-up. Two asymptomatic patients were receiving the conditioning regimen when SARS CoV-2 was diagnosed. The median age at diagnosis was 39,2 (1-72) years. Five patients were children (1-12 years) and 17 were adults (19-72 years). Eleven patients (50%) had comorbidities, the most frequent being diabetes and hypertension. Fever, cough and diarrhea were the symptoms more frequently observed and occurred in 13 (76.4%), 7 (41.2%), and 5 (29.4%) of the 17 symptomatic patients, respectively. Symptoms such as anosmia and dysgeusia, which have been frequently associated with COVID-19 were not observed in this series. Eleven of the symptomatic patients (64.7%) showed altered CT or X-ray at diagnosis. Glass ground opacities were the images more frequently seen (63.6%). The median lymphocyte count was 619.5 (0-2,604) /mL. C-reactive protein and d-dimer ranged from 0.65 to 339 ng/mL and from 0.39 to 4,530 mg/L, respectively. Four (18%) HSCT recipients died (1 AUTO, 2 HAPLO, 1 MRD). COVID-19 was the cause of death in two of them. In the remaining two HAPLO HSCT recipients, KPC co-infection followed by septic shock had a major role in patients' death. Median age of patients who died was 39 (11-59) years, and two of them had comorbidities (hypertension and chronic lung disease). Conclusions. Symptoms of COVID-19 mimic other respiratory virus infections and specific diagnosis is mandatory. Interstitial pneumonia was frequent (around 65%). Clinical outcome of SARS Cov-2 infection or COVID-19 was moderate in the majority of the patients in the present series. However, the mortality rates observed in HSCT recipients (14.3% in AUTO; 20% in ALLO) were higher than in general population. Asymptomatic cases were seen in almost 30% of the patients, suggesting that frequent screening is necessary to control transmission in HSCT centers. Disclosures No relevant conflicts of interest to declare.

The advent of newer second-line medical therapies (SLMT) for immune thrombocytopenia (ITP) has contributed to decreased rates of splenectomy, following a trend to avoid or delay surgery. We aimed to characterize the long-term outcomes of laparoscopic splenectomy (LS) for ITP at our institution, examining differences in LS efficiency when performed before or after SLMTs.Adults with primary ITP who underwent LS between 2002 and 2016 were identified. Retrospective review of electronic medical records was supplemented with telephone interviews. Treatment response was defined according to current guidelines as complete responders (CR), responders (R), and non-responders (NR). Kaplan-Meier estimates assessed relapse-free rates, and predictors of long-term response were investigated using logistic regression.109 patients met inclusion criteria, from which 42% were treated with an SLMT before referral to LS. LS was completed in all cases, with no conversions or intraoperative complications. The perioperative morbidity was 7.3%, including 3 deep vein and 2 portal vein thrombosis, one reoperation for bleeding, and no mortalities. Splenectomy was initially effective in 99 patients (CR + R = 90.8%), and 10 patients were NR. At a median 62-month follow-up, 25 patients relapsed, resulting in a 68% CR + R rate. Proportion of CR + R was similar in patients who previously received SLMT and those who did not (61 vs. 76.7%, p = 0.08). CR + R patients were younger (45 vs. 53, p = 0.03), had higher preoperative platelet counts (36 vs. 19, p = 0.01), and experienced a higher increment in platelet counts during hospital stay (117 vs. 38, p 0.001) as well as 30-days postoperatively (329 vs. 124, p 0.001). Only a robust response in platelet count at 30-days postoperatively was independently associated with long-term response (OR 1.005, p = 0.006).LS was curative in 68% of patients, with no statistically significant difference when performed before or after SLMTs. Outcomes remain challenging to predict preoperatively, with only a robust increase in platelet counts on short term being associated with long-term response.

Introduction The Hematopoietic Stem Cell Transplantation Service (HSCT) of the Amaral Carvalho Hospital began its activities in August 1996. At first, an Excell® spreadsheet was applied, in which all the information concerning the HSCT performed in our service were included. The use of this tool had the purpose of organizing the HSCT service information. In 2009, we started to send data to the Center for International Blood and Marrow Transplant Research (CIBMTR). Due to the beginning of this new activity and the large amount of information requested by CIBMTR, an improvement in the previously used platform was felt necessary. Today there are 12 Brazilian active centers in the CIBMTR. According to a recent CIBMTR report (info request #1807-14), our center has reported an average of 43% of all first transplants performed in Brazil and reported to the CIBMTR in the last 4 years. Objective Due the lack of resources for large investments in the technology information area as a public center, and the need to improve the tool in use, another software was proposed to speed up the data collection, to organize the internal database and to report the data to the CIBMTR. Materials and Methods In 2013 a database was developed in Access® (Microsoft® Office), containing all the information requested in the CIBMTR forms and necessary for the analysis and control of the Service results. After entering all the data, the program is able to generate a report containing all information necessary to complete the pre-HSCT forms (Forms 2804, 2814, 2400 and 2402). Within the program there are links to carry out the risk calculation of VOD (hepatic veno-occlusive disease)/SOS (hepatic sinus obstructive syndrome) and DRI (disaster risk index). There is also a calculator for the HCT-CI (Hematopoietic cell transplant specific comorbidity index), using as a template the site http://www.hctci.org/Home. The post-HSCT data can also be inserted, making it possible to use the database to fill up all the CIBMTR follow-up forms. Results and Discussion With the development of this database program a great improvement was achieved in the quality of organization of internal data and in the timely report to the CIBMTR. Between 2011 and 2014 the average percentage of forms submitted within the proposed deadline was 25.5%, while between 2015 and July 2018 this average increased to 80.5%. Currently, approximately 200 HSCT are reported annually and around 900 post-transplant follow-up forms are sent. Conclusion As the new tool was developed by the data manager, we have the possibility to edit the program according to our needs and with the information requested by CIBMTR. Idealized for routine use, this tool allowed the organization of the information, in a large HSCT center with few resources, helping us to report 100% of the HSCT performed to the CIBMTR since 2009.

The rising success rate of solid organ (SOT) and haematopoietic stem cell transplantation (HSCT) and modern immunosuppression make transplants the first therapeutic option for many diseases affecting a considerable number of people worldwide. Consequently, developing countries have also grown their transplant programs and have started to face the impact of neglected tropical diseases (NTDs) in transplant recipients. We reviewed the literature data on the epidemiology of NTDs with greatest disease burden, which have affected transplant recipients in developing countries or may represent a threat to transplant recipients living in other regions. Tuberculosis, Leprosy, Chagas disease, Malaria, Leishmaniasis, Dengue, Yellow fever and Measles are the topics included in this review. In addition, we retrospectively revised the experience concerning the management of NTDs at the HSCT program of Amaral Carvalho Foundation, a public transplant program of the state of São Paulo, Brazil.