Toxicity Profile of PEG-Asparaginase in Adult Patients With Acute Lymphoblastic Leukemia in Brazil: A Multicenter Cross-Sectional Study.

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/m2 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.

Outcomes of HIV-associated Burkitt Lymphoma in Brazil: High treatment toxicity and refractoriness rates - A multicenter cohort study.

BACKGROUND: Although the increased use of combined antiretroviral therapy (cART) has decreased the incidence of lymphomas HIV-associated, Burkitt lymphoma (BL) incidence remains stable. Reported outcomes on HIV-associated BL from developed countries seem to corroborate that the regimens do not need to be tailored to the HIV-positive population. MATERIALS AND METHODS: This is a retrospective multicenter cohort study from Brazil, including HIV-positive patients aged 15 years and above diagnosed with BL. RESULTS: A total of 54 patients were included. Median age was 39 years (range, 15-64). At diagnosis, advanced disease was found in 86% and 52% had a CD4+ count lower than 200 cells/mm3. Five patients died before starting any regimen. Among the remaining 49 patients, most were treated with Hyper-CVAD (53%) and CODOX-M IVAC (18%). Rituximab was used in frontline in only 16% of the patients. Primary refractory disease was found in 14%. A treatment-related mortality of 38.7% and a complete response rate of 44.9% were found. At 4 years, estimated overall survival (OS) was 39.8%. All relapsed and primary refractory patients eventually died. Remaining patients died from infections (24/34), despite antimicrobial prophylaxis and associated cART. CONCLUSION: Early mortality and toxicity were higher in our cohort than in developed countries. A faster diagnosis, better understanding of the biology of the disease, establishment of low toxicity regimens, inclusion of rituximab and improvement of supportive care may decrease the mortality of HIV-associated BL in developing countries.

Real-life Outcomes on Acute Promyelocytic Leukemia in Brazil - Early Deaths Are Still a Problem.

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.