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Blood Adv ; 5(17): 3436-3444, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34461632


The expression of CD20 in precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD20+ ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD)-negative status postinduction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD-negative complete remission in patients with high-risk ALL. Given bortezomib's activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20+ precursor B-ALL. We conducted a phase 2 study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (aged >14 years) with CD20+, Philadelphia-negative precursor B-ALL; bone marrow MRD negativity at the end of induction was the primary end point. From December 2017 through August 2019, a total of 35 patients were enrolled. End-of-induction MRD-negative status was achieved in 70.9% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD-negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, event-free survival and overall survival rates were 78.8% (95% confidence interval, 66-94) and 78.7% (95% confidence interval, 65.8-94), respectively. There was no significant increase in toxicity with bortezomib and rituximab compared with the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen was active and well tolerated in de novo CD20+ Philadelphia-negative precursor B-ALL. This trial was registered with the Clinical Trials Registry-India as CTRI/2017/04/008393(

Linfoma de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Bortezomib/uso terapêutico , Criança , Humanos , Células Precursoras de Linfócitos B , Rituximab
Blood Adv ; 5(5): 1178-1193, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33635331


The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.

Citarabina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Transplante de Células-Tronco , Adulto Jovem