RESUMEN
Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults. Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen, has been proven effective in this patient subgroup. Nonetheless, low- and middle-income countries (LMICs) may present limited access to standard care treatments implemented elsewhere, warranting the need for further research to improve outcomes among vulnerable populations. In this study, we present the outcomes in terms of safety and effectiveness of using a modified CALGB 10403 regimen to reflect drug and resource availability in LMICs. Modifications included the use of Escherichia coli asparaginase,6-mercaptopurine instead of thioguanine and the use of rituximab among patients with CD20+. A total of 95 patients with a median age of 23 (range, 14-49) years treated with this modified scheme were prospectively assessed at 5 centers in Mexico and 1 in Guatemala. Among these, 87.8% achieved a complete response after induction. During follow-up, 28.3% of patients relapsed. Two-year OS rate was 72.1%. Factors associated with worse OS included hyperleukocytosis (hazard ratio [HR], 4.28; 95% confidence interval [CI], 1.81-10.10) and postinduction minimal residual disease (HR, 4.67; 95% CI, 1.75-12.44). Most patients presented hepatotoxicity (51.6% and 53.7% during induction and consolidation, respectively), and the treatment-related mortality was 9.5%. Overall, results highlight that implementing a modified CALGB 10403 regimen in Central America is feasible, and it is associated with improvements in clinical outcomes and a manageable safety profile.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Asparaginasa/efectos adversos , Mercaptopurina , Rituximab/uso terapéutico , Inducción de RemisiónRESUMEN
BACKGROUND: In the past decades, long-term survival outcomes for younger patients with acute myeloid leukemia (AML) have improved. Nonetheless, developing nations might be lagging behind, highlighting the need to assess real-world outcomes in such regions. METHODS: We performed a multicenter retrospective study, which included patients with AML diagnosed between January 2013 and December 2017 from 13 centers in Mexico. RESULTS: A total of 525 patients with AML met the inclusion criteria and were included in the study. Median age for the entire cohort was 47 years. The patients were classified according to cytogenetic risk: favorable 16.0%, intermediate 55.6%, and unfavorable 28.4%. Most patients received intensive chemotherapy (80.2%), and among these 74.1% underwent a 7 + 3 induction regimen. A complete remission was achieved in 71.3% of patients. Induction-related mortality occurred in 17.8% and we identify the following as independent risk factors: >60 years (odds ratio [OR] 2.09 [1.09-4.02]), Eastern Cooperative Oncology Group >2 (OR 4.82 [2.46-9.43]), prior solid tumor (OR 3.8 [1.24-11.59]) and active infection (OR 1.82 [1.06-3.12]). Further, allogeneic hematopoietic stem-cell transplantation (AlloHSCT) was performed in 8.2% in CR1. The 3-year overall survival (OS) was 34.8%. In a multivariate analysis, several factors were independently associated with a worse OS, including secondary AML (hazard ratio [HR] 2.14 [1.15-4.01]) and unfavorable cytogenetic risk (HR 1.81 [1.16-2.82]), whereas maintenance therapy (HR 0.53 [0.32-0.86]) and AlloHSCT (HR 0.40 [0.17-0.94]) were associated with better OS. CONCLUSIONS: This is the first multicenter report analyzing AML survival in Mexico. Challenges in this setting include a high induction-related mortality and low AlloHSCT rate, which should be addressed to improve outcomes.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Sistema de Registros , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Países en Desarrollo , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , México/epidemiología , Persona de Mediana Edad , Inducción de Remisión , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
Hemophagocytic lymphohistiocytosis is a syndrome characterized by pathological immune activation that may occur as either a primary a familial disorder (associated with genetic mutations), or as a sporadic condition, associated to infections, malignancies or autoimmune diseases. The clinical picture is characterized by a disproportionate inflammation that causes fever, cytopenias, splenomegaly, bone marrow hemophagocytosis, hypertriglyceridemia and hypofibrinogenemia. Syndrome-related mortality is high, so it is important to maintain a high index of suspicion and start early treatment with immunochemotherapy and bone marrow transplantation in primary and refractory cases. In this article, we review the clinical manifestations, pathology, diagnosis and treatment of these patients.