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Outcomes in acute myeloid leukemia (AML) are dependent on patient- and disease-characteristics, treatment, and socioeconomic factors. AML outcomes between resource-constrained and developed countries have not been compared directly. We analyzed two cohorts: from São Paulo state, Brazil (USP, n = 312) and Oxford, United Kingdom (OUH, n = 158). USP cohort had inferior 5-year overall survival compared with OUH (29% vs. 49%, adjusted-p=.027). USP patients have higher early-mortality (23% vs. 6% p<.001) primarily due to multi-resistant Gram-negative bacterial and fungal infections. USP had higher 5-year cumulative incidence of relapse (60% vs. 50%, p=.0022), were less likely to undergo hematopoietic stem cell transplant (HSCT) (28% vs. 75%, p<.001) and waited longer for HSCT (median, 23.8 vs. 7.2 months, p<.001). Three-year survival in relapsed patients was worse in USP than OUH (10% vs. 39%, p<.001). Our study indicates that efforts to improve AML outcomes in Brazil should focus on infection prevention and control, and access to HSCT. [ABSTRACT FROM AUTHOR]

Immunosuppressive therapy (IST) using horse antithymocyte globulin (h-ATG) combined with cyclosporine (CsA) and eltrombopag is the standard care for aplastic anemia (AA) in patients without a suitable matched donor. However, in many countries, h-ATG use has been discontinued, leaving rabbit ATG (r-ATG), which has a lower response rates and poorer survival, as the only alternative. In previous studies, alemtuzumab (ALZ), a humanized monoclonal antibody targeting CD52, combined with CsA resulted in an adequate ORR in AA patients. This study describes a multicenter, international retrospective analysis of ALZ for treating AA. We analyzed a series of patients who received subcutaneous ALZ for AA in four centers in Brazil and the United Kingdom from March 2009 to January 2024. We analyzed 64 ALZ treatments in 61 AA adult patients, 76% with SAA or very severe aplastic anemia (VSAA). Overall response rate (ORR) was 59.4% at 12 months (complete: 21.9%, partial: 37.5%). Cumulative incidence (CI) of response was 54.7% at 6 months, and 59.4% at 12 months. Younger patients (under 65) had higher CI of response (67% vs. 31%, P=0.03), as well as patients treated with a total dose of 103 mg (70% vs. 38%, P=0.02). Overall survival (OS) was 86% at 1 year, 78% at 2 years, and 70% at 4 years, significantly higher in responders (90% vs. 44%, P<0.0001). Adverse events were of low grade, and infectious events were infrequent. Subcutaneous ALZ is a feasible, effective, and safe alternative to r-ATG for AA patients requiring immunosuppressive treatment where h-ATG access is limited., (Copyright © 2024 American Society of Hematology.)

Outside of clinical trials, few studies have addressed the outcomes of Ph+ acute lymphoblastic leukemia (ALL) in adults, especially from developing world. In this study, we conducted a multicenter analysis on the outcomes of patients aged > 15 years with Ph+ ALL, aiming to get to know an overview of the Brazilian experience as well as to explore baseline factors associated with relapse and mortality in our setting. Over these 10 years, patients were treated with diverse protocols, all of them always combined with a frontline tyrosine-kinase inhibitor. A total of 123 Ph+ ALL patients was included. Imatinib was the first line TKI in 97 %. The complete response rate was 79 %. The early death rate was 15 %, being associated with increasing age at diagnosis (p = 0.06). The use of intensive versus attenuated induction regimen was not associated with higher induction mortality (p = 0.99). Overall, 29 % of patients aged ≤ 60 years underwent allogeneic transplantation, 87 % in first CR. 4-year overall survival (OS) and relapse-free survival were 25 % and 24 %, respectively. The incidence of relapse (death as a competitor) was 29 %, while the non-relapse mortality was 42 %. Only age was independently associated with OS, and lactate dehydrogenase level and central nervous disease at diagnosis were related to relapse in our cohort. This is the first historical cohort multicenter study on Ph+ ALL from Brazil. Reporting these outcomes is essential to encourage public policies to expand access to new drugs and transplantation in middle-income countries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Currently, pediatric-inspired regimens are commonly applied to adults with acute lymphoblastic leukemia (ALL) after the recent recognition that these protocols improve survival. While asparaginase in whatever available formulation is a key component of modern treatment of ALL, many adult oncologists and hematologists struggle to deal with its particular toxicities in clinical practice. We reviewed toxicity outcomes of pegylated asparaginase (PEG-ASP) in adults with ALL treated in 3 reference centers in Brazil., Patients and Methods: This was a cross-sectional retrospective chart-review study encompassing patients aged 15 years and older diagnosed with ALL or ambiguous-lineage leukemia who received at least one dose of PEG-ASP, regardless of the adopted regimen., Results: A total of 57 patients were included (age range, 15-57 years). Most patients (70%) received 2000 IU/m 2 as the initial dose, by intravenous route (72%). The incidence of thromboembolic events was 17.5%, and the main site was cerebral venous sinus (4/10). Thrombosis was more frequent in patients receiving second-line treatment. In obese patients, grade 3 hepatotoxicity and hyperbilirubinemia were more common. Clinical pancreatitis (grade 3 or higher) was found in 2 of 57 cases. PEG-ASP had to be discontinued in 19.3% of exposed patients (11/57)., Conclusion: By reviewing the medical charts of adult patients with ALL from 3 reference centers, we found that our incidence of thrombotic and hepatic adverse events is similar to those reported in other trials involving PEG-ASP. Usually these effects should not preclude further use of the drug because most events are manageable in routine clinical practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aplastic anemia (AA) is a rare disorder characterized by suppression of bone marrow function, which can progress to myelodysplastic syndrome (MDS) or to acute myeloid leukemia (AML). To determine if there are characteristics in bone marrow biopsies in children and adults previously diagnosed with acquired AA, which could predict progression to MDS, we evaluated 118 hypocellular bone marrow biopsies from adults (76 patients) and children (42) diagnosed initially with acquired AA previously to any treatment. Histology was reviewed according to a detailed protocol including Bennett and Orazi criteria for hypocellular myelodysplastic syndrome (h-MDS) and Bauman et al. criteria for refractory cytopenia of childhood (RCC). Twelve patients (10.2%; 6 children and 6 adults) progressed to MDS after a median time of 56 months. Criteria described by Bennett and Orazi suggestive of h-MDS in bone marrow biopsies were detected in 16 cases (13.5%; 8 adults and 8 children), and none in patients that progressed to MDS/AML. Twenty adults' biopsies (26.3%) had the histological criteria used for the diagnosis of pediatric RCC, and none showed MDS/AML evolution. Ten children (23.8%) were reclassified morphologically as RCC, and only one progressed to MDS. In this population with acquired aplastic anemia (AAA), no histological/immunohistochemical (H/IHC) bone marrow findings could discriminate patients with higher risk for myeloid clonal progression, which questions the diagnosis of h-MDS/RCC based only on the finding of dysplasia in the cases without increased blasts and/or the characteristic genetic abnormalities., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to disclose regarding the current paper. The Institutional Review Board approved this retrospective study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disease which is treated on the basis of small studies, making the literature still scarce of reports, especially of those conducted in Latin America. Here we intend to describe clinical characteristics, rates of response, survival and second neoplasms in HCL patients treated in a reference center in Brazil. All patients diagnosed with HCL between July/1987 and Jun/2018 were included in this analysis. Fifty-four patients were included in this analysis. Median age at diagnosis was 55 years (range, 26-88), with 37% being above 60 years-old. Most patients were treated with cladribine in our cohort (n = 36; 68%), administered through intravenous continuous infusion. Remaining patients were firstly managed with splenectomy (n = 7; 13%), IFN (n = 6; 11%) and rituximab (n = 2; 4%). In a univariate analysis, platelet count and B2M level at diagnosis were statistically associated with CR achievement (p = 0.004 and p = 0.024, respectively). A median follow-up time of 9 years was calculated. Estimated 10-year overall survival was 91.1% (95% confidence interval, 77-97). In this cohort, 10 patients had any second neoplasm, diagnosed before or after HCL. Regarding the sites of cancer, 69% were of skin - 8/16 carcinoma-type and 3/16 melanoma-type. Our response and survival data are similar to those reported by literature, which reaffirms the role of purine analogs in current HCL management. With a very long follow-up we also have observed a high incidence of second neoplasm., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Although a considerable improvement in survival of patients with acute promyelocytic leukemia (APL) has been seen over the past decades, real-life outcomes seem to be worse than those reported by prospective studies. We aim to describe clinical characteristics and outcomes of adult patients diagnosed with APL in an academic hospital from the University of Sao Paulo., Patients and Methods: We retrospectively reviewed the medical charts of 61 patients with APL diagnosed between January 2007 and May 2017. Baseline clinical features and follow-up data were collected, focusing on early toxicity variables such as infection, bleeding, and thrombosis in the first 30 days from diagnosis., Results: Among the 61 patients with APL, 54 received any chemotherapy. All patients also received all-trans retinoic acid (ATRA). Bleeding events were the main cause of death before receiving chemotherapy. Most patients belonged to the intermediate (43%) and high-risk (41%) groups, according to Sanz score. The '7 + 3 + ATRA' regimen was the most used regimen (n = 38). An early death rate of 20% was found, predominantly owing to sepsis. After a median follow-up of 5 years, only 1 relapse was diagnosed. The overall survival at 5 years was 59%., Discussion: In comparison with prospective trials with ATRA-based regimens, we found an inferior overall survival, mostly on account of a high early-death rate. Our results are in line with other real-life retrospective reports published in the past decades., Conclusion: Results of real-life studies differ from those found by prospective trials. Accordingly, early actions and supportive care are still needed, aiming to decrease toxicity, especially in developing countries., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Acute lymphoblastic leukemia (ALL) in adults is an invariably aggressive and rare disease. Its treatment is based on the use of multidrug regimens, which have been improved since the 1970s. Few published data are available on the results of adult ALL treatment in Latin America., Materials and Methods: We retrospectively analyzed the data from 59 patients with ALL treated from 2009 to 2015 at Hospital of Clinics of University of São Paulo, using an adapted German Multicenter ALL (GMALL) protocol (07/2003)., Results: The median patient age was 35 years (range, 16-71 years), with 76% of new cases of B-cell lineage. Central nervous system involvement was present in 29%. Most patients were in the high-risk group, using the original GMALL criteria (68%). The early death rate was 17%, preventing early evaluation of the response in these patients. Despite a reasonable complete remission rate (76%), most patients eventually died of sepsis, especially during the induction phase and salvage regimens. The median overall survival was 17 months., Conclusion: Intensified chemotherapy protocols for adult ALL have succeeded in achieving better survival rates in adults, especially younger adults. The low overall survival found with GMALL in Brazil's public hospital denotes the importance of optimizing the adaptations of international protocols for treatment of ALL in nondeveloped countries and, in parallel, improving supportive care in public services., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Fanconi Anemia (FA) is a rare and heterogeneous genetic syndrome. It is associated with short stature, bone marrow failure, high predisposition to cancer, microcephaly and congenital malformation. Many genes have been associated with FA. Previously, two adult patients with biallelic pathogenic variant in Breast Cancer 1 gene (BRCA1) had been identified in Fanconi Anemia-like condition., Clinical Report: The proband was a 2.5 year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features. Her parents were third degree cousins. Routine screening tests for short stature was normal., Methods: We conducted whole exome sequencing (WES) of the proband and used an analysis pipeline to identify rare nonsynonymous genetic variants that cause short stature., Results: We identified a homozygous loss-of-function BRCA1 mutation (c.2709T > A; p. Cys903*), which promotes the loss of critical domains of the protein. Cytogenetic study with DEB showed an increased chromosomal breakage. We screened heterozygous parents of the index case for cancer and we detected, in her mother, a metastatic adenocarcinoma in an axillar lymph node with probable primary site in the breast., Conclusion: It is possible to consolidate the FA-like phenotype associated with biallelic loss-of-function BRCA1, characterized by microcephaly, short stature, developmental delay, dysmorphic face features and cancer predisposition. In our case, the WES allowed to establish the genetic cause of short stature in the context of a chromosome instability syndrome. An identification of BRCA1 mutations in our patient allowed precise genetic counseling and also triggered cancer screening for the patient and her family members., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)