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Hypereosinophilia (HE) is defined as an eosinophil count exceeding 1500 cells/microL in peripheral blood in two tests, performed with an interval of at least one month and/or anatomopathological confirmation of HE, with eosinophils comprising more than 20% of all nucleated cells in the bone marrow. Hypereosinophilic syndrome (HES) indicates the presence of HE with organ involvement due to eosinophil action, which can be classified as primary (or neoplastic), secondary (or reactive), and idiopathic. Cardiac involvement occurs in up to 5% of cases in the acute phase and 20% of the chronic phase of the disease, ranging from oligosymptomatic cases to fulminant acute myocarditis or chronic restrictive cardiomyopathy (Loeffler endomyocarditis). However, the degree of cardiac dysfunction does not directly correlate with the degree of eosinophilia. The cardiac involvement of HES occurs in three phases: initial necrotic, thrombotic, and finally necrotic. It can manifest as heart failure, arrhythmias, and thromboembolic phenomena. The diagnosis of cardiopathy is based on multimodality imaging, with an emphasis on the importance of echocardiography (echo) as the primary examination. TTE with enhanced ultrasound agents can be used for better visualization, allowing greater accuracy in assessing ventricular apex, and myocardial deformation indices, such as longitudinal strain, may be reduced, especially in the ventricular apex (reverse apical sparing). Cardiac magnetic resonance imaging allows the characterization of subendocardial late gadolinium enhancement, and endomyocardial biopsy is considered the gold standard in diagnosing cardiopathy. Treatment is based on the etiology of HES.

Background: Primary Raynaud's phenomenon (pRP) is difficult to distinguish from secondary (sRP). Although nailfold capillaroscopy (NFC) may detect early alterations, no universal criteria yet discriminate between pRP from sRP., Objectives: To create and validate two NFC scores that could distinguish pRP from sRP and that could predict systemic sclerosis (SSc), respectively., Methods: We performed NFC on two separate cohorts with isolated RP, and recorded number of capillaries per field, enlarged/giant capillaries, crossed/bizarre patterns, microhemorrhages, neoangiogenesis, rarefaction, edema, blood flow velocity, stasis. By multivariate regression analysis, we evaluated the adjusted prognostic role of these features in a derivation cohort of 656 patients. Results were used to construct algorithm-based prognostic scores (A and B). These scores were then tested on a confirmation cohort of 219 patients., Results: Score A was unable to discriminate sRP from pRP (low negative predictive values with high positive predictive values for any cut-point); score B was unable to discriminate progression to SSc or a SSc-spectrum disorder (low positive predictive values with high negative predictive values for lower cut-points)., Conclusion: NFC patterns, believed as specific, showed low discriminatory power and on their own are unable to reliably discriminate sRP from pRP or predict evolution to SSc.

Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Introduction: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome. After the introduction of imatinib mesylate (IM) in 2000, the natural history of the disease changed. Data on the treatment of CML with IM are from randomized clinical trials. Establishing whether these results can be reproduced or if caution is needed when extrapolating data to the general population with CML is essential., Objectives: To evaluate the molecular response (MR) in patients with chronic-phase CML (CML-CP) not included in clinical studies and correlate them with the responses obtained in clinical trials., Methods: Between January 2007 and January 2017, 227 patients newly diagnosed with CML-CP treated with IM as first-line treatment were included. This study is an observational, retrospective, and single-center study., Results: At a median follow-up time of 7.3 years, 60.3% of the 227 patients who started IM were still on IM. Early molecular response (EMR) at 3 and 6 months was achieved by 74.2% and 65%, respectively. The median time to a MMR was nine months. The MR4.0 and MR4.5 were 67.2% and 51.1%, respectively. The overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) of the patients who exclusively used IM were 91%, 91%, and 85.1%, respectively., Conclusion: The results presented are similar to those described in prospective and randomized trials, demonstrating that the outcomes are reproducible in the real world. EMR at 3 and 6 months reflects better long-term responses, including higher rates of deeper molecular responses. Considering treatment costs, the absence of literature evidence of an impact on overall survival demonstrated by first-line second-generation tyrosine kinase inhibitors (TKIs), and the global OS of 85.8%, imatinib mesylate (IM) is still an excellent therapeutic option., (© 2023. The Author(s).)

Background: Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients´ medical records were retrospectively reviewed., Results: One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, ≥ 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had ≥ 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG ≥ 2 were identified as independent risk factors for reduced survival., Conclusions: Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries., (© 2022. The Author(s).)

Introduction: Systemic Mastocytosis comprises a group of neoplastic diseases characterized by clonal expansion and infiltration of mast cells into several organs. The diagnosis and treatment of this disease may be challenging for non-specialists., Objective: Make suggestions or recommendations in Systemic Mastocytosis based in a panel of Brazilian specialists., Method and Results: An online expert panel with 18 multidisciplinary specialists was convened to propose recommendations on the diagnosis and treatment of Systemic Mastocytosis in Brazil. Recommendations were based on discussions of topics and multiple-choice questions and were graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Chart., Conclusion: Twenty-two recommendations or suggestions were proposed based on a literature review and graded according to the findings., Competing Interests: Conflicts of interest AMMC, AMS, AFS, FT, FLN, GFP, JLB, LLM, LFE, MGB and MVA declare no conflicts of interest. EDRPV has received research grants from Novartis, AbbVie and Onconova and presented scientific data in on behalf of Celgene and Novartis. FPSS has received research grants from Novartis, participated in advisory boards at Novartis and presented scientific data on behalf of Novartis, BMS, Amgen, AbbVie, Pfizer and Astellas. FSS has participated in advisory boards at Novartis. GAP has participated in advisory boards and presented scientific data on behalf of Novartis. KBBP has participated in advisory boards at Novartis, Astellas and GSK and presented scientific data on behalf of Novartis, Pintpharma, Wyeth, Janssen and EMS. PGB has participated in advisory boards at Novartis, Sanofi, AstraZeneca and Takeda. RCA has presented scientific data on behalf of Novartis., (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Treatment-free remission (TFR) is a new goal of chronic myeloid leukemia (CML) therapy. TFR is feasible when the patient has achieved a deep and stable molecular response and met the criteria required to ensure its success. Treatment discontinuation should not be proposed to the CML patient if minimum conditions are not met. In Brazil, for example, molecular tests (BCR::ABL1) are not broadly available, making it difficult to monitor the patients adequately., Objective: In this sense, providing TFR recommendations for Brazilian physicians are therefore necessary. These recommendations include the main criteria checklist to start the TKIs treatment discontinuing process in patients diagnosed with CML and the population-eligible characteristics for treatment discontinuation., Method: Age, risk score at diagnosis, TKI treatment duration, BCR::ABL1 transcripts type, depth of the molecular response for treatment discontinuation, treatment adherence, patient monitoring and withdrawal syndrome are essential factors to consider in TFR. After TKI discontinuation, BCR::ABL1 transcripts monitoring should be more frequent. When a major molecular response loss is observed during the monitoring of a patient in TFR, the TKI treatment should be resumed., Conclusion: These recommendations should serve as a basis for medical professionals interested in proposing TKI discontinuation for CML patients in clinical practice. It is important to highlight that, despite the benefits of TFR for the patients and the health system, it should only be feasible following the minimum standards proposed in this recommendation., Competing Interests: Conflicts of interest All authors received grants from Novartis to participate in the expert panel. No other competing interests were declared., (Copyright © 2022. Published by Elsevier España, S.L.U.)

This observational, multicenter study aimed to report the clinical evolution of COVID-19 in patients with chronic myeloid leukemia in Latin America. A total of 92 patients presented with COVID-19 between March and December 2020, 26% of whom were severe or critical. The median age at COVID-19 diagnosis was 48 years (22-79 years), 32% were 60 years or older, and 61% were male. Thirty-nine patients presented with at least one comorbidity (42.3%). Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. There was one case of reinfection. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; p  = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (100, 89, 50, and 33%, respectively; p  < 0.001).

Extraordinary progress has been made over the last decade in the treatment of multiple myeloma with the incorporation of new drugs, particularly proteasome inhibitors, immunomodulators, and monoclonal antibodies. The combined use of innovative drugs, already in the first lines of treatment, has led to an expressive increase in the survival of these patients. However, the approach to relapse remains a great challenge, and the disease continues to be incurable. In this scenario, modern immunotherapy has gained the limelight, especially with its recent use of CAR-T cells in clinical trials, as in the case of multiple myeloma, having the BCMA as the primary target. The results are impactful in the treatment of multiple myeloma patients who have had multiple relapses and are triple- and penta-refractory. In this Consensus, we have brought together a group of experts in multiple myeloma to discuss and forward their recommendations for the future, which we hope is very near, incorporating the CAR-T in our country., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

This manuscript summarizes the results of the consensus meeting composed of hematologists and cardiologists to establish recommendations for the prevention and follow-up of cardiovascular (CV) risk in patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKIs) from the point of view of clinical practice and from the perspective of hematology consultation. In the first medical appointment, the CV risk factors should be identified to perform the baseline risk stratification, based on the Brazilian Guideline of Dyslipidemia and Atherosclerosis Prevention Update (risk levels: very high, high, intermediate and low). Once stratified, the treatment of the CV risk factors should be administered. If the patient presents risk factors, such as hypertension, diabetes, renal disease, smoking and hypercholesterolemia, the evaluation and initial treatment may be done by the hematologist, being an option the request for evaluation by a specialist. If the patient has a history of previous CV disease, we recommend referral to a specialist. As the CV risk score is dynamic and the control of risk factors can reduce the patient risk, this expert consensus recommends that the re-evaluation of the CV risk after the baseline should be performed at 3 months, 6 months and 12 months. After this period, it should be done annually and, for specific patients, at the clinician's discretion. The evaluation of the baseline CV risk and the safe administration of a TKI allow the patient to benefit from the maximum treatment, avoiding unwanted effects., (Copyright © 2020 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Treatment-free survival (TFS) in chronic myeloid leukemia (CML) is a new goal. This prospective study aims to evaluate imatinib discontinuation's feasibility and safety in patients with deep molecular response MR4 (BCR-ABL1 < 0.01 % IS)., Methods: Study was approved by the ethical committee and registered at Clinicaltrials.gov (NCT03239886). Incluision criteria were: age ≥ 18y, chronic phase, first-line imatinib for 36 months, MR4 for 12 months, no previous transplant or resistance. Imatinib was resumed when two samples confirmed the loss of MMR. The primary endpoint was molecular recurrence-free survival (MRFS) at 24 months. Lymphocyte subpopulations were counted in peripheral blood before discontinuation., Results: 31 patients were included from Dec/2016 until Oct/2017. Median age was 54years, 58 % male, 58 % low Sokal, 65 % b3a2 transcripts, and 61 % were in MR4.5. Imatinib therapy's median time was 9.7y (3-14.9 y), median time of MR4 was 6.9y (1.6-10.3y). MRFS at 24 months was 55 % (95 % CI 39-75). Thirteen patients relapsed, 46 % after six months of discontinuation, and all patients recovered MMR. Median time to recover MMR was one month. MR4.5 was the only factor associated with MRFS. NK cells proportion at baseline was lower in patients with only MR4 who relapsed after discontinuation., Conclusion: With a median duration of sustained MR4 above five years, as recommended by most TKI discontinuation guidelines, the TFS was similar to previous studies. Only MR4.5 was associated with lower risk of relapse. Further studies are needed to evaluate whether patients with only MR4 and low NK cell levels are suitable for discontinuation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Few data are available regarding epidemiology and outcomes of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) in Latin America. Therefore, current models for MPN treatment are based in large cohorts of patients from Europe and North America. In this paper, we conducted a retrospective study to evaluate thrombotic and bleeding events in a cohort of patients with MPN from a reference center in Brazil. A total of 334 patients were included, being essential thrombocythemia the most common diagnosis. Here, we found that 41% of the MPN patients had a thrombotic event prior to the diagnosis. Thrombosis was more frequent in patients under 60 years-old. In a multivariable model, only JAK2 V617F mutation (OR 2.57 95% CI 1.58-4.18, p < 0.001) and presence of two cardiovascular risk factors (OR 1.90 95% CI 1.21-2.98, p < 0.005) were significant for thrombosis. The risk of thrombosis was similar among all subtypes of MPN. Cumulative incidence of thromboembolic event at 5 years from diagnosis was 5.8% (95% CI 3.5-8.9), which is similar to previous studies. The high incidence of thromboembolic events in younger patients suggests that socioeconomic disparities might have a role in the outcomes of MPN.

Objectives: The outcomes of refractory and relapsed acute myeloid leukemia (AML) patients in developing countries are underreported, even though the similar classic regimens are widely used., Methods: We conducted a retrospective comparison of "MEC" (mitoxantrone, etoposide, and cytarabine) and "FLAG-IDA" (fludarabine, cytarabine, idarubicin, and filgrastim) in adults with first relapse or refractory AML., Results: In total, 60 patients were included, of which 28 patients received MEC and 32 received FLAG-IDA. A complete response (CR) rate of 48.3% was observed. Of the included patients, 16 (27%) died before undergoing bone marrow assessment. No statiscally significant difference in CR rate was found between the two protocols (p=0.447). The median survival in the total cohort was 4 months, with a 3-year overall survival (OS) rate of 9.7%. In a multivariable model including age, fms-like tyrosine kinase 3 (FLT3) status, and stem-cell transplantation (SCT), only the last two indicators remained significant: FLT3-ITD mutation (hazard ratio [HR]=4.6, p<0.001) and SCT (HR=0.43, p=0.01)., Conclusion: In our analysis, there were no significant differences between the chosen regimens. High rates of early toxicity were found, emphasizing the role of supportive care and judicious selection of patients who are eligible for intensive salvage therapy in this setting. The FLT3-ITD mutation and SCT remained significant factors for survival in our study, in line with the results of previous studies.

The way rheumatoid arthritis is treated has changed dramatically with the introduction of anti-tumor necrosis factor (anti-TNF) biologics. Nevertheless, many patients still have less than adequate control of their disease activity even with these therapeutic regimens, and current knowledge fails to explain all the data already gathered. There is now a wide range of drugs from different classes of biologic disease-modifying anti-rheumatic drugs available (and soon this number will increase significantly), that provides the opportunity to address each patient as a particular case and thereby optimize medical intervention. Currently available biologics for the treatment of rheumatoid arthritis apart from anti-TNF-based therapies are reviewed, along with an analysis of the new insights they provide into the pathogenesis of the disease and a discussion of future prospects in the area.

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Unlabelled: Hypertrophic cranial pachymeningitis (HCP) is an uncommon disorder characterized by localized or diffuse thickening of the dura mater, and it usually presents with multiple cranial neurophaties. It has been associated with a variety of inflammatory, infectious, traumatic, toxic and neoplasic diseases, when no specific cause is found the process is called idiopathic. The infectious cases occur in patients under systemic immunosuppression, which have an evident contiguous source or those who have undergone neurosurgical procedures. We describe a case of a 62-year-old immunosuppressed woman with diabetes and rheumatoid arthritis, which had HCP and osteomyelitis of the skull base caused by pseudomonas aeruginosa, presenting with headache and diplopia. We believe this is the second documented case of pachymeningitis secondary to this microorganism. As a multifactorial disease, it is essencial to determine the specific causative agent of HCP before making treatment decisions, and great care is needed with immunocompromised patients., Keywords: Pseudomonas aeruginosa; Hypertrophic pachymeningitis; Ophtalmoplegia, optical neuropathy; Osteomyelitis; Skull base.

Background: Zidovudine (AZT) and didanosine (ddI) are antiretroviral drugs widely used in AIDS patients. Hypokalemia and hypomagnesemia are frequently encountered in AIDS patients using AZT and/or ddI., Objective: To verify the effects of AZT and ddI on rat renal function submitted to normal diet, low potassium diet and magnesium-free diet., Methods: Glomerular filtration rate and renal hemodynamic were measured in Wistar rats submitted to a normal or a potassium-depleted diet. The animals were given AZT, ddI for 15 days. Six groups of rats were studied: normal diet, normal diet + AZT, normal diet + ddI, low K diet, low K diet + AZT and low K diet + ddI. Three additional groups of rats submitted to magnesium depletion for 15 days were also studied: magnesium-free diet, magnesium-free diet + AZT and magnesium-free diet + ddI., Results: AZT and didanosine did not modify renal function of rats on a normal diet. However, in hypokalemic rats, both drugs produced a decrease in glomerular filtration rate and in renal blood flow consequent to renal vasoconstriction and associated with alterations in tubular function (characterized by an increased fractional excretion of sodium). Hypomagnesemia induced a decrease in glomerular filtration rate and in renal blood flow only in AZT-treated rats., Conclusion: Our data suggest that hypokalemia predisposes to AZT and ddI nephrotoxicity, while hypomagnesemia predisposes only to AZT nephrotoxicity. Thus, chronic AZT and ddI administration may produce acute renal failure in AIDS patients with hypokalemia and/or hypomagnesemia. Serum K and Mg levels should be carefully monitored in these patients.