RESUMO
BACKGROUND: Intermittent treatment with tyrosine kinase inhibitors (TKIs) is an option for elderly chronic myeloid leukemia (CML) patients who are often candidates for life-long treatment. MATERIALS AND METHODS: The Italian phase III multicentric randomized Optimize TKIs Multiple Approaches (OPTkIMA) study aimed to evaluate if a progressive de-escalation of TKIs is able to maintain the molecular remission (MR)3.0 and to improve Health-Related Quality of Life (HRQoL) in CML elderly patients. RESULTS: A total of 215 patients in stable MR3.0/MR4.0 were randomized to receive an intermittent TKI schedule 1 month ON-1 month OFF for 3 years (FIXED arm; n = 111) vs. a progressive de-escalation TKI dose up to one-third of the starting dose at the 3rd year (PROGRESSIVE arm; n = 104). Two hundred three patients completed the 3rd year of OPTkIMA study. At the last follow-up, MR3.0 loss was 27% vs. 46% (P = .005) in the FIXED vs PROGRESSIVE arm, respectively. None of these patients experienced disease progression. The 3-year probability of maintaining the MR3.0 was 59% vs. 53%, respectively (P = .13). HRQoL globally improved from the baseline to the 3rd year, without any significant difference between the 2 arms. After the 3rd year, the proportion of patients who was address to TKI discontinuation in the 2 arms was 36% (FIXED) vs. 58% (PROGRESSIVE) (P = .03). CONCLUSIONS: The intensification of intermittent TKI therapy is associated with a higher incidence of MR3.0 loss, but those patients who maintain the MR3.0 molecular response at the end of the study have been frequently considered eligible for TFR. The HRQoL generally improved during the de-escalation therapy in both randomization arms.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Inibidores de Proteínas Quinases , Qualidade de Vida , Humanos , Idoso , Masculino , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Feminino , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Itália , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
Spontaneous splenic rupture (SSR) is a rare life-threatening emergency. In hematological settings, it is uncommon in acute myeloid leukemia (AML). We report an atypical case of SSR in a 73-year-old male with AML where a prompt imaging ultrasound assessment played a key role. Performed noninvasively at bedside, it allowed rapid imaging diagnosis, confirming its essential role even in the presence of hematological disease.
RESUMO
BACKGROUND: Intermittent treatment with TKIs is an option for the great majority (70%-80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. METHODS: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0 ) and to improve Health Related Quality of Life (HRQoL). RESULTS: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0 /MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients' HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). CONCLUSIONS: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0 /MR4.0 in 81% of the patients during the first 12-24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Itália , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores Sexuais , Fatores de TempoRESUMO
Hepatosplenic T cell lymphoma (HSTCL) is a type of hematologic neoplasia with a poor prognosis and a high frequency of refractoriness to conventional chemotherapy. The results obtained by high dose chemotherapy followed by autologous stem cells transplantation seem to be a more effective option but still unsatisfactory. Also the role of allogeneic stem cell transplantation is still unclear, although the few cases reported on the literature would seem to show good results in overall survival rates. In this paper, we reported the patient׳s medical history affected by a αß variant of hepatosplenic T cell successfully rescued with a haploidentical transplant.
RESUMO
The aim of the present study was to investigate the outcome of 94 adult patients with myelodysplasia (MDS) who received an allogeneic stem cell transplant between January 1995 and September 2010 in two Italian hematology centers. At the time of transplant, 53 patients (56%) had relapsed/refractory disease. The cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was 33% (95% confidence interval [CI] 21-45%) and 78% (95% CI 66-90%), respectively. The cumulative incidence of transplant-related mortality (TRM) at 100 days was 13% (95% CI 6-21%). The 2-year progression free survival (PFS) and overall survival (OS) were 41% (95% CI 31-51%) and 49% (95% CI 38-59%), respectively. On multivariate analysis, advanced disease stage at transplant was the major independent variable associated with an inferior 2-year PFS (HR 3.66, 95% CI 1.98-6.76) and OS (HR 3.68, 95% CI 1.95-6.93). Use of an alternative donor was an independent variable associated with TRM (HR 3.18, 95% CI 1.31-7.72). In conclusion, our data suggest that disease status at the time of transplant is the major predictor for improved PFS and OS, and treatments required to reach this goal may have value in leading to an improved outcome.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Recidiva , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do TratamentoRESUMO
Side effects of chemo-radiotherapy reduce the quality and also the survivability of patients. The consequent fatigue and infections, related to myelodepression, act to reduce the dose-intensity of the protocol. Late side effects of chemo-radiotherapy include secondary tumours, acute myeloid leukemias and cardiotoxicity. Side effects of chemotherapy are related to oxidative stress produced by the treatment. Oxidative stress also reduces the efficacy of the treatment. Antioxidative treatment with natural (dietetic) or chemical agents has been reported to reduce the toxicity of chemo-radiotherapy and improve the efficacy of treatment. We here report our experience with SEQEX, an electromedical device that generates Extremely Low Frequency ElectroMagnetic Fields (ELF-EMF) to produce endogenic cyclotronic ionic resonance, to reduce myelotoxicity consequent to ABVD protocol in patients with Hodgkin's lymphoma.
Assuntos
Antineoplásicos/efeitos adversos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Campos Eletromagnéticos , Doença de Hodgkin/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Hemoglobinas/metabolismo , Doença de Hodgkin/imunologia , Doença de Hodgkin/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacosRESUMO
Contamination of autologous graft by tumor, in addition to incomplete tumor eradication, can partly explain why relapse remains the commonest cause of treatment failure after autologous stem cell transplantation (ASCT) in patients with malignant hematologic disorders. Monitoring of minimal residual disease (MRD) is now recognized as an important diagnostic tool for assessment either of the response to treatments aimed at maximal cytoreduction and the individual risk of relapse. In order to improve cure rates, many strategies to achieve in vivo or in vitro reduction, if not eradication, of residual disease have been proposed. We discuss the significance of MRD and the role of purging in the ASCT setting, focusing on acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma and follicular lymphoma.