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Abstract Sjogren’s disease (SjD) is an autoimmune disease that is characterized not only by the sicca symptoms it causes but also by its systemic nature, which is capable of several and not yet fully understood extraglandular manifestations. To gain a clearer understanding of these manifestations as well as a better practical approach, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of the extraglandular manifestations present in ESSDAI (EULAR Sjogren´s syndrome disease activity index), followed by a voting panel with recommendations for clinical practice. This publication is complementary to others already published and covers cutaneous and hematological manifestations, with prevalence data generated by a meta-analysis of 13 clinical or laboratory manifestations and 6 clinical management recommendations.

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia. Patients who achieve sustained deep molecular response are eligible for treatment discontinuation. DES-CML is an ongoing, phase 2 multicentric discontinuation trial. Adult patients with CML in chronic phase with typical BCR::ABL1 transcripts, stable deep molecular response (MR4.5 IS) for two years, and no previous resistance were eligible. Patients underwent a phase of TKI dose de-escalation for six months before discontinuation. TKI was reintroduced at the previous dose if the patient lost major molecular response (MMR) at any time. This study aimed to assess the impact of BCR-ABL transcript kinetics during TKI de-escalation and discontinuation phases on treatment-free survival. So far, the study recruited 41 patients, and 38 patients discontinued therapy (4 were in the second discontinuation attempt). Eleven patients lost MMR, one during the de-escalation phase and ten after discontinuation. 24-month treatment-free survival was 66% (95% CI: 48-84%) in a median follow-up of 7 (1–30) months. No patient lost hematological response or had disease progression. A higher rate of molecular relapses occurred in patients with fluctuating BCR::ABL1 levels after the discontinuation phase (with loss of MR4.5, but no loss of MMR) (P=0.04, HR-4.86 (1.03-22.9) but not confirmed in the multivariate analysis. The longer duration of TKI treatment (P=0.03, HR-1.02, 95%CI - 1.00-1.04) and MMR (P=0.004, HR-0.95, 95%CI - 0.92-098) were independent factors of a lower relapse rate.

WHERE WE ARE?Patients with advanced-stage classical Hodgkin lymphoma (cHL) have a good prognosis. In most countries, the first-line treatment has been, for at least a couple of decades, the ABVD protocol. Depending on several factors such as age, presence of bulky disease, or extranodal involvement, around 75-80% of patients are cured with this regimen1. However, there are now new treatment recommendations for advanced-stage cHL. After 6 years of follow-up, the ECHELON-1 study showed overall survival (OS) benefit for brentuximab vedotin with AVD versus the standard ABVD2. This has never happened in previous direct comparative trials. Although the BV+AVD was already approved for first-line treatment of advanced-stage cHL patients, based on the gain of progression-free survival (PFS) published a couple of years ago, a benefit in OS makes a much stronger case. Peripheral neuropathy was a special concern, with about 2 out of 3 patients treated with BV+AVD experiencing some form of symptom. Mainly it was grades I 1 and 2, and the symptoms did resolve or improved in almost 90% of cases2. But the BV-AVD reign has already been challenged. The SWOG1826 study is a randomized, multicenter, phase 3 trial, that compares the combination of nivolumab with AVD (nivo-AVD) versus BV-AVD3. This is a large trial, with almost 1000 patients, that included patients between 12 and 83 years. The 1-year PFS rate was 94% versus 86% (HR 0.48, 99%CI 0.27-0.87; p=0.0005), in favor of Nivo-AVD. OS was similar (99% vs 98%), with a short median follow-up of 12.1 months. Interesting that both arms of this study were for a limited number of 6 cycles, something different that is normally done with checkpoint inhibitors (usually until the progression of the disease, unacceptable toxicity, or up to 2 years). So, a longer follow-up will be paramount to see if this advantage for nivo-AVD will hold in time. The toxicity profile was largely as expected and no new safety signals in both arms. On the other hand, the HD21 study looked at the association between BV and a similar backbone of the escalated BEACOPP (eBEACOPP), known as BrECADD4. This new regimen was compared in a multicenter, randomized, phase 3 non-inferiority trial, with the standard eBEACOPP. Using a PET-adapted strategy, where interim PET negative patients completed 4 total cycles versus 6 total cycles in PET positive, BrECADD was non-inferior to eBEACOPP. The 3y-PFS rate was 94.9% versus 92.3%, with a median observation time of 40 months. These impressive results compare favorably with BV-AVD in the ECHELON-1 study (6y PFS of 82.3%) and with Nivo-AVD in the SWOG study (1y PFS of 94%), but with all the restrictions of comparing different trials.WHAT TO EXPECT FOR THE FUTURE?Clearly, in one of the lymphomas with the best overall prognosis, the treatment landscape evolved. There are now at least 3 new options for the treatment of advanced-stage cHL in the first line, with better results than ABVD, the standard for a long time. As we continue to improve efficacy, toxicity remains an important issue. Longer follow-ups will be needed to see if we can have great results without impact in our patient's quality of life.

Introduction: The new world health organization (WHO) classification on lymphoid neoplasms, the WHO-HAEM5, renames the former group that double-hit lymphomas were in as “diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements (DLBCL/HGBL-MYC/BCL2)”. This is mainly to highlight that the presence of MYC and BCL2 rearrangements form a unique phenotype, different than the MYC and BCL6 rearrangements (present in the former classification). Those lymphomas are composed of large or intermediate or blastoid cells, with aggressive clinical course and tendency to be resistant to standard chemotherapy. It's a group ideal for new therapies, such as the bispecifics and CAR T-cells, but lack data to support this since are underrepresented in clinical trials. Retrospective studies, with its inherit bias, consistently points to worst prognosis and poor outcomes with standard RCHOP treatment. How to best approach this hard-to-treat lymphoma is still a matter of debate. Treatment considerations: Roughly 65% of patients with DLBCL are cure with 6 cycles of RCHOP. When considering this regimen for HGBL, event-free survival (EFS) has been reported as low as 20% in 3 years. More intensive regimens, like R-DA-EPOCH and R-CODOX/M-IVAC, could increase this response, based on retrospective studies, with EFS 3y close to 80%. The role of autologous transplant as consolidation is controversial, and it's not routinely indicated. However, there are data that patients treated with RCHOP could increase progression-free survival (PFS) with this strategy, perhaps eliminating the difference between more intensive regimens. The lack of a direct comparison in a randomize phase 3 study between RCHOP or more intensive protocols precludes a firm conclusion. In the Alliance/CALGB 50303 study, that compared RCHOP with R-DAEPOCH in patients with DLBCL and PMBCL, there were no differences in 2y PFS between arms. But the number of patients with MYC rearrangement was too small to any conclusion regarding HGBL. Dunleavy et al conducted a phase 2 study with R-DA-EPOCH in 53 patients with MYC-rearranged DLBCL (24 were double-hit). EFS 4y was 71% and overall-survival (OS) 4y was 77%. Although this looks pretty good compared to the historic RCHOP, it's not a randomize study. New therapies have emerged as possible rescue in the relapsed/refractory DLBCL population, a group of patients with a dismal prognosis. The chimeric antigen receptor (CAR) T-cells have become a new standard of care for those patients, when available. Albeit with a small number of patients, the three main products (axi-cell, tisa-cell and liso-cell), used for rescue of DLBCL patients, had shown activity against HGBL. That holds true in latter lines and as a first salvage treatment, as the recent trials comparing with autologous transplant. The zuma-12 is a phase 2 study with axi-cell as first-line of treatment with high-risk DLBCL patients, a population enriched with HGBL. Early reports are impressive, with nearly 80% of complete remissions. However, long term follow-up will be necessary to see with the responses are durable. Bispecifics are other very important players on that field, with the first reports of high activity in high-risk DLBCL, even after CAR T-cell failure. Conclusions: HGBL is an aggressive form of lymphoma, with tendency of a worst prognosis with conventional treatment. Intensive regimens seem to fare better than RCHOP, although with more toxicity and no randomize studies supporting this indication. New treatments, mainly CAR T-cells and bispecifics, are very promising and possibly will became standard of care for such patients but were in the therapy algorithm is still to be decide.

Objective: T-cell Brazil project started in April 2017 an ambispective study focusing to collecting epidemiological and clinical data from the most frequent subtypes of PTCL. Our goals are to obtain the frequency of subtypes by the five Brazilian macro regions; to investigate the clinical and biology characteristic; to create a routine pathological revision and to evaluate the OS, EFS in 5 years of follow-up. Methodology: Thirteen nine centers had approved by their Ethical Committee and using REDcap Platform by Vanderbilt are registering their cases. Descriptive and bivariate analyses, then it was applied Kaplan-Meier method and log-rank test to obtain survival estimates, using IBM-SPSS v.24 Results: The median age was 55 years (19-95); 56% male; Almost 72% had advanced stages, 28% ECOG ≥ 2; the distribution of main subtypes was: 31% PTCL-NOS; 18% ALCL, ALK-; 16% ATL; 13% ENKTL nasal and nasal type; 11% AITL; 7% ALCL, ALK+; 6% others (Table 1). 50% of patients were alive and the 24-month PFS and OS was 36% and 50%, respectively. OS by main subtypes was 48% PTCL-NOS; 61% ALCL, ALK-; 33% ATL; 46% ENKTL nasal/nasal type; 48% AITL; 80% ALCL, ALK+. Conclusion: This is the first experience cover all over the country, focusing also an educational and of interchanging experience network among the multidisciplinary health team in Brazil. The target of 500 was exceeded; however, the registry will go on until December as planned. All cases have been reviewed both in the registry and by pathologist Committee, and we esteem some cases will be excluded for different reasons and anyway it will help for future analyses if the number of registers is higher.

Objective: T-cell Brazil project started in April 2017 an ambispective study focusing to collecting epidemiological and clinical data from the most frequent subtypes of PTCL, among them the ATL. As of July 2022 T-cell Brazil database contained 81 (16%) ATL out of 520 registered cases. Our goals are to describe demographic and clinical features, analyze the overall and progression-free survival (OS and PFS), and try to identify factors that could influence outcome. Methodology: Brazilian Registry using REDcap Platform by Vanderbilt realized descriptive and bivariate analyses, then it was applied Kaplan-Meier method and log-rank test to obtain survival estimates, and besides that, it was used the Cox Regression to identify any factor that could influence the OS and PFS. Results: The median age was 52 years (24-91); 32 (39%) male; the majority of clinical subtypes were 52% lymphoma type; 81% received chemotherapy. The best response assessment after first-line treatment was: progression or no response in 31%; 26% complete response; 21% partial response, 21% not available (NA) due to death or on treatment; 34% of patients were alive and the 24-month OS and PFS was 33% and 21%, respectively. As predictors for PFS and OS were B symptom and elevated LDH values. Conclusion: This study, even recognizing a limited sample size, highlights the poor prognosis associated with ATL, mainly acute and lymphoma type, with high mortality rates. Hence, apparently, a good shot, it would be one of the bases for the prevention of ATL to establish a disease entity of “chronic active HTLV-1 infection” that defines high-risk carriers for ATL development, and then, enables preventive intervention.

O linfoma difuso de grandes células B é o tipo mais comum de linfoma agressivo. Os pacientes que não respondem à terapia de primeira linha têm um prognóstico ruim. O transplante de medula óssea representa um tratamento de salvamento eficaz e estabelecido para aqueles pacientes, com potencial curativo. O transplante autólogo utiliza células-tronco do paciente para salvamento após a quimioterapia mieloablativa em altas doses, enquanto o transplante alogênico depende de uma célula-tronco diferente para um efeito enxerto-versus-linfoma. Com toxicidade distinta e capacidade de induzir a remissão, essas terapias têm grande valor no manejo de pacientes com linfoma difuso de células B recidivante e refratário.

Diffuse large B-cell lymphoma is the most common type of aggressive lymphoma. Patients that don’t respond to first-line therapy have a poor prognosis. Bone marrow transplant represents an effective and established salvage treatment for those patients, with curative potential. Autologous transplant uses the patient stem cell for rescue after high-dose myeloablative chemotherapy, while allogenic transplant relies on a different stem cell for a graft-versus-lymphoma effect. With distinct toxicity and capacity to induce remission, those therapies have great value in the management of patients with relapsed and refractory diffuse large B-cell lymphoma.

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.

There has been a rapid increase in the volume of genomic data gathered from different cancers, this has helped to develop new tumor classifications as well as to select better tailored therapies for the patients. Some of the genomic markers identified are also prognostic and predictive factors. Additionally, many technologies have been used to investigate these alterations, each with different benefits and caveats. The Genomics Committee from the Sociedade Brasileira de Oncologia Clínica (SBOC) put together a group of specialists, from different regions of Brazil that work both in the private and public scenario, to gather and organize the information regarding the utility of somatic mutation testing in solid tumors. This special article summarizes their recommendations on how to better incorporate this information into clinical practice.