RESUMEN
ABSTRACT: T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.
Asunto(s)
Leucemia-Linfoma de Células T del Adulto , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Mutación , Recurrencia , Enfermedad Crónica , Células ClonalesAsunto(s)
Anticuerpos Antivirales/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , COVID-19/inmunología , Quimioterapia de Inducción/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , SARS-CoV-2/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/sangre , COVID-19/virología , Niño , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/virología , PronósticoRESUMEN
PURPOSE: We tested whether blinatumomab (Blina) is effective as a toxicity-sparing alternative to first-line intensive chemotherapy in children and young persons (CYP) with B-ALL who were chemotherapy-intolerant or chemotherapy-resistant. METHODS: Data were collected for consecutive CYP (age 1-24 years) with Philadelphia chromosome-positive or Philadelphia chromosome-negative B-ALL who received Blina as first-line therapy. Blina was given as replacement for postremission intensive chemotherapy to patients with chemotherapy intolerance or resistance. Blina responders received further chemotherapy (Blin-CT) or first remission hematopoietic stem-cell transplant (Blin-HSCT) if indicated. Event-free survival (EFS) and overall survival (OS) of the Blin-CT group were compared with those of matched controls treated with standard chemotherapy in the UKALL 2003 trial. Events were defined as death, relapse, or secondary cancer. RESULTS: From February 2018 to February 2023, 105 patients were treated, of whom 85 were in the Blin-CT group and 20 were in the Blin-HSCT group. A majority of Blin-CT patients received Blina for chemotherapy intolerance (70 of 85, 82%), and the group had a higher-risk profile than unselected patients with B-ALL. Blina was well tolerated with only one patient having a grade 3/4-related toxicity event, and of the 60 patients who were minimal residual disease-positive pre-Blina, 58 of 60 (97%) responded. At a median follow-up of 22 months, the 2-year outcomes of the 80 matched Blin-CT group patients were similar to those of 192 controls (EFS, 95% [95% CI, 85 to 98] v 90% [95% CI, 65 to 93] and OS, 97% [95% CI, 86 to 99] v 94% [95% CI, 89 to 96]). Of the 20 in the HSCT group, three died because of transplant complications and two relapsed. CONCLUSION: Blina is safe and effective in first-line treatment of chemotherapy-intolerant CYP with ALL.