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(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.
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During a 2-year period, 157 consecutive episodes of respiratory virus infections that occurred in 130 patients with upper or lower respiratory tract infection were analyzed for respiratory viruses. A respiratory virus was identified in 75 episodes (48%), and several viruses were found in 13 episodes: there were a total of 56 influenza A virus infections, 14 respiratory syncytial virus infections, 8 adenovirus infections, 8 infections with parainfluenza virus types 1 or 3, and 7 enterovirus infections. On multivariate analysis, the only variable that predicted progression to pneumonia in patients with an upper respiratory tract infection was the presence of respiratory syncytial virus, whereas lymphocytopenia had a nonsignificant trend. Also, among the 38 patients who had pneumonia at any time during the episode, both respiratory syncytial virus and lymphocytopenia were commonly found. For both epidemiological and therapeutic considerations, frequent screening for respiratory viruses should be incorporated into the routine diagnostic study of patients with hematologic malignancies.
Assuntos
Neoplasias Hematológicas/complicações , Infecções Respiratórias/virologia , Adenoviridae/isolamento & purificação , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Neoplasias Hematológicas/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Estudos Prospectivos , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Fatores de RiscoRESUMO
About 15-20% of patients with Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy ± radiotherapy still die following relapse or progressive disease. The outcome might be influenced by gene polymorphisms influencing chemotherapy metabolism. We studied 126 patients with HL treated with the ABVD regimen. We analyzed glutathione S-transferases (GSTT1, GSTM1 and GSTP1), cytochromes P450 (CYP3A4 and CYP2D6), UGT1A1 and BLMH gene polymorphisms and their association with clinical and outcome variables. Patients with a GSTM1 genotype associated with extensive or ultrahigh activity had a probability of 93.8% to achieve a complete response, while the remainder of the patients had a probability of 82.3% (p = 0.04). This variable maintained its statistical significance in multivariate analysis (hazard ratio 3.7, 95% confidence interval 1-13, p = 0.05). Patients with an extensive or ultrahigh GSTM1 genotype had better prognostic factors than those with poor or intermediate genotypes (hemoglobin level, p = 0.003; serum albumin, p = 0.05; and International Prognostic Score, p = 0.038). Thus, in the treatment of HL, clinical determinants might be more relevant than the pharmacogenetic parameters analyzed to date.
Assuntos
Doença de Hodgkin/genética , Doença de Hodgkin/terapia , Farmacogenética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Enzimático do Citocromo P-450/genética , Feminino , Seguimentos , Genótipo , Glutationa Transferase/genética , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo Genético , Estudos Prospectivos , Radioterapia/efeitos adversos , Resultado do Tratamento , Adulto JovemAssuntos
Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/etiologia , Proteínas de Fusão Oncogênica , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Fatores de Poliadenilação e Clivagem de mRNA , Benzamidas , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-IdadeRESUMO
Bendamustine is a alkylating agent with a purine-like benzamidazole ring currently approved in Europe for indolent non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma. Our aim was to analyze retrospectively the efficacy and toxicity of bendamustine in NHL and CLL in Spain in the bendamustine Compassionate Use Program. Patients with relapsed/refractory NHL or CLL were eligible. Any regimen containing bendamustine was eligible. 109 patients were included from 22 institutions. Forty-nine patients had indolent NHL, 18 aggressive NHL and 42 CLL, being 44 patients (40%) refractory to previous treatment. 63% of patients had adverse events grade 3-4, mainly hematological. Overall response rate (ORR) was 66%, complete responses 30%. ORR observed in refractory patients was 45%. The median progression-free survival (PFS) was 13 months. Outcome was influenced by histology, number of previous treatments, resistance to previous chemotherapy and type of response achieved with bendamustine. Alone or in combination, bendamustine shows a meaningful clinical antitumor activity in patients with relapsed or refractory NHL or CLL, with an acceptable toxicity profile.
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Antineoplásicos Alquilantes/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Compostos de Mostarda Nitrogenada/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Cloridrato de Bendamustina , Ensaios de Uso Compassivo , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Compostos de Mostarda Nitrogenada/efeitos adversos , Estudos Retrospectivos , Espanha , Resultado do TratamentoRESUMO
Respiratory viruses (RVs) are known to be major causes of morbidity and mortality in recipients of hematopoietic stem cell transplants (HSCTs), but prospective long-term studies are lacking. We prospectively screened all adult HSCT recipients (172 allogeneic [alloHSCT] and 240 autologous [autoHSCT]) who underwent transplantation during a 4-year period (1999 to 2003) for the development of a first episode of symptomatic upper respiratory tract infections and/or lower respiratory tract infections (LRTI) by an RV. RVs studied were influenza A and B viruses (n=39), human respiratory syncytial virus (n=19), human adenoviruses (n=11), human parainfluenza viruses 1 to 3 (n=8), human enteroviruses (n=5), human rhinoviruses (n=3), and the recently discovered human metapneumoviruses (n=19). During the study, 51 and 32 cases of RV symptomatic infections were identified of alloHSCT and autoHSCT recipients (2-year incidence, 29% and 14%, respectively). Risk factors for progression of upper respiratory tract infection to LRTI included severe (<0.2x10(9)/L) and moderate (<0.2x10(9)/L) lymphocytopenia in alloHSCT (P=.02) and autoHSCT (P=.03). Death from LRTI was attributed to an RV in 8 alloHSCT recipients. Symptomatic RV had no effect on 2-year outcomes, with the possible exception of influenza A and B virus infections in autoHSCT: these were associated with nonrelapse mortality (P=.02). In conclusion, this prospective trial allows an estimation of the minimum incidence of a first RV infection in adult HSCT recipients and identifies risk factors for acquisition of an RV infection and progression to LRTI; this should aid in the design of future studies. In addition, human metapneumovirus should be added to the potentially serious causes of RV infections in HSCT.
Assuntos
Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Adulto , Idoso , Saúde da Família , Feminino , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Fatores de Risco , Fatores de Tempo , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Vírus/isolamento & purificaçãoRESUMO
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