RESUMO
AIM: The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. MATERIALS AND METHODS: All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was ad- ministered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. RESULTS: From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. CONCLUSION: The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established dur- ing controlled clinical trials.
Assuntos
Antineoplásicos/uso terapêutico , Arabinonucleosídeos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Arabinonucleosídeos/efeitos adversos , Arabinonucleosídeos/farmacocinética , Ensaios Clínicos como Assunto , Humanos , Injeções Intravenosas , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacocinética , Intervalo Livre de Progressão , RecidivaRESUMO
The introduction of acute leukemia chemotherapy programs in clinical practice improved effectiveness of treatment and patients' survival rate. However there is a high incidence of anticancer drugs toxicity leading to a decrease in therapeutic effect of treatment. Acute lymphoblastic leukemia (ALL) is a leader among oncohematological pathologies in childhood and adolescence. Its share is 20 % of all malignancies and up to 75% of all leukemias. Treatment for ALL in childhood is one of the most impressive achievements of medicine in recent years. Modern chemotherapy programs can achieve healing in 80 % of patients with ALL, and the researchers are facing new challenges to achieve a high safety profile of treatment. Chemotherapy toxicity frequency varies from 5% to 30 %. This review presents summarized literature analysis on the clinical symptoms of toxic reactions and the ways to prevent and correct developed adverse drug reactions.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Thirty four patients with mucormycosis in 10 hospitals of St. Petersburg were observed in 2004-2013. The most frequent underlying diseases of mucormycosis were acute leukoses (64%). In 100% of the patients mucormycosis developed as a nosocomial infection. The risk factors, etiology, basic clinical signs and strategy in the treatment of mucormycosis were analyzed.
Assuntos
Antifúngicos/uso terapêutico , Infecção Hospitalar/microbiologia , Leucemia Linfocítica Crônica de Células B/microbiologia , Leucemia Mieloide Aguda/microbiologia , Mucormicose/microbiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Infecção Hospitalar/complicações , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/tratamento farmacológico , Mucormicose/mortalidade , Estudos Prospectivos , Rhizopus/efeitos dos fármacos , Rhizopus/crescimento & desenvolvimento , Rhizopus/isolamento & purificação , Fatores de Risco , Federação Russa , Análise de SobrevidaAssuntos
Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças do Sistema Nervoso Central/induzido quimicamente , Criança , HumanosRESUMO
AIM: To evaluate the efficiency of the original ALL-MB-2002 protocol within the multicenter study of treatment of acute lymphoblastic leukemia (ALL) in children. SUBJECTS AND METHODS: A total of 1873 primary patients with ALL aged 1 to 18 years, of whom 1544 patients were enrolled in this study, were notified at 36 clinics of Russia and Belarus from April 15, 2002, to January 1, 2008. RESULTS: With the median observation of 4.12 years, 7-year event-free survival (EFS) was 73 +/- 13%; overall survival (OS) 78 +/- 2%; relapse-free survival 82 +/- 1%. The rates of EFS and OS were equal and amounted to 76 +/- 2 and 80 +/- 2% in the standard-risk group (SRG) and intermediate-risk group (ImRG), respectively. In the high-risk group (HRG) patients, EFS and OS were as high as 30 +/- 6 and 37 +/- 6%, respectively. The frequency of relapses with central nervous system lesion was as much as 4.7% in all the patients, 6-year cumulative risk for isolated neurorecurrences being 2.5% in the SRG patients. Adolescents, patients with the baseline leukocytosis (more than 100 x 10(9)/l), and those with a splenic size of over 4 cm or more from the costal arch margin had substantially worse survival rates. A poor early response to therapy (on induction days 8 and 15) was also associated with its lower efficiency. CONCLUSION: Despite a considerable rise in the number of centers and a slight increase in the intensity of therapy, the results of the new ALL-MB-2002 protocol are as minimum equivalents obtained in the use of the previous ALL-MB-91 protocol. A significant improvement in the overall results of therapy and a reduction in the cumulative risk for isolated neurorecurrences were noted in the ImRG patients.