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INTRODUCTION: Chronic myeloid leukemia (CML) is a malignant clonal disorder of hematopoietic stem cells characterized by a translocation of genetic material between chromosomes 9 and 22 resulting in the BCR-ABL fusion oncogene expression. Nilotinib is a potent second-generation tyrosine kinase inhibitor available as first line treatment. Among side effects QTc interval prolongation, pancreatitis, metabolic disorders and skin reactions are the most commonly seen. CASE REPORT: Here we describe a rare case of lichen planopilaris eruption that developed during therapy with nilotinib. MANAGEMENT & OUTCOME: Nilotinib dosage was reduced together with introduction of hydroxychloroquine with progressive improvement of alopecia. DISCUSSION: Collaboration with dermatologist and nilotinib dose reduction allowed to continue the drug maintaining major molecular response and patient's quality of life.
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Exantema , Leucemia Mielógena Crónica BCR-ABL Positiva , Liquen Plano , Resistencia a Antineoplásicos , Exantema/inducido químicamente , Proteínas de Fusión bcr-abl , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Liquen Plano/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas , Calidad de VidaRESUMEN
BCR-ABL1 kinase domain mutation testing in tyrosine kinase inhibitor (TKI)-resistant Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) patients is routinely performed by Sanger sequencing (SS). Recently, next-generation sequencing (NGS)-based approaches have been developed that afford greater sensitivity and straightforward discrimination between compound and polyclonal mutations. We performed a study to compare the results of SS and NGS in a consecutive cohort of 171 Ph+ ALL patients. At diagnosis, 0/44 and 3/44 patients were positive for mutations by SS and NGS respectively. Out of 47 patients with haematologic resistance, 45 had mutations according to both methods, but in 25 patients NGS revealed additional mutations undetectable by SS. Out of 80 patients in complete haematologic response but with BCR-ABL1 ≥0·1%, 28 (35%) and 52 (65%) were positive by SS and NGS respectively. Moreover, in 12 patients positive by SS, NGS detected additional mutations. NGS resolved clonal complexity in 34 patients with multiple mutations at the same or different codons and identified 35 compound mutations. Our study demonstrates that, in Ph+ ALL on TKI therapy, NGS enables more accurate assessment of mutation status both in patients who fail therapy and in patients with minimal residual disease above 0·1%.
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Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Anciano , Toma de Decisiones Clínicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Neoplasia Residual/epidemiología , Cromosoma Filadelfia/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Glucocorticoid treatment is the standard initial therapy for patients with immune thrombocytopenia (ITP). Despite a rate of 60-80% of initial remissions, only 30 to 50% of adults have a sustained response after discontinuation. Second line options are splenectomy, thrombopoietin-receptor agonists (TPO-RAs), rituximab and intravenous immunoglobulin. Third line treatments include a mix of immunosuppressive drugs (e.g. azathioprine, ciclosporin, etc.). Recently international guidelines have proposed a treatment algorithm formalizing TPO-RAs and splenectomy as second and third line respectively, confirming splenectomy as second line choice only in emergency. Here we present a single center observational retrospective study of eltrombopag as second line treatment. We evaluated 48 adult primary chronic ITP patients since 2003. Forty-four out of 48 patients received a first line treatment with glucocorticoids. Twenty-two (61%) patients needed a second line treatment: 18 received eltrombopag, 3 a second course of steroid and one patient underwent splenectomy. Every patient before starting eltrombopag or receiving splenectomy underwent bone marrow examination. Overall response rate to eltrombopag was 94% with a CR rate of 76% and a PR of 23%; only one patient was non responder, underwent splenectomy and received subsequent treatment with rituximab, romiplostim and cyclosporin obtaining CR. One patient developed an autoimmune pancytopenia about a month after starting TPO-RA and in addition to eltrombopag received steroid and rituximab with blood count improvement. After a median follow up of 21,1 months (range 0,4-64,7 months) 16 patients (89%) are still on therapy maintaining response. As regards safety, gastrointestinal side effects were rare and low grade; only one patient discontinued eltrombopag after few weeks, because of dizziness. One patient had a relapse of deep venous thrombosis while no major bleeding complications were observed. Our real-life single center experience confirms efficacy and safety of eltrombopag as second line treatment in chronic ITP patients.
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Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Receptores de Trombopoyetina/agonistas , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Although a wealth of efficacy and safety data is available for many tyrosine kinase inhibitors used in chronic myeloid leukemia (CML), there is a dearth of information on their impact on patients' health-related quality of life (HRQOL). The primary objective of this study was to evaluate HRQOL and fatigue outcomes in patients with CML receiving first-line therapy with nilotinib. METHODS: This was a multicenter, prospective study enrolling 130 patients with chronic-phase CML. HRQOL and fatigue were evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and its validated Fatigue module at the baseline and then at 3, 6, 12, 18, and 24 months. The primary prespecified HRQOL endpoints defined in the study protocol for longitudinal analysis were the Physical Functioning, Social Functioning, Role Functioning, and Fatigue scales. The remaining scales were investigated on an exploratory basis. RESULTS: The rate of baseline compliance with the HRQOL assessment was 95.4% (124 of 130), and the rate of overall compliance with HRQOL forms was 91%. Among the 4 prespecified primary HRQOL endpoints, statistically significant improvements over time were found for Physical Functioning (P = .013), Role Functioning (P = .004), and Fatigue (P < .001). Clinically meaningful improvements were found already 3 months after the treatment start. The baseline patient self-reported fatigue severity was an independent predictive factor for the achievement of a major molecular response with an odds ratio of 0.960 (95% confidence interval, 0.934-0.988; P = .005). CONCLUSIONS: For most patients, HRQOL improvements with nilotinib occur during the early phase of therapy and are maintained over time. Also, a more systematic HRQOL evaluation during the diagnostic workup of CML may help to predict clinical outcomes. Cancer 2018;124:2228-37. © 2018 American Cancer Society.
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Fatiga/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Fatiga/etiología , Fatiga/psicología , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/psicología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Autoinforme/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenAsunto(s)
Vacuna nCoV-2019 mRNA-1273/efectos adversos , Vacuna BNT162/efectos adversos , COVID-19/prevención & control , ChAdOx1 nCoV-19/efectos adversos , Púrpura Trombocitopénica Idiopática/etiología , SARS-CoV-2 , Vacunación/efectos adversos , Corticoesteroides/uso terapéutico , Adulto , Enfermedad de Hashimoto/complicaciones , Hemorragia/etiología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Recurrencia , Rituximab/uso terapéutico , Adulto JovenRESUMEN
Lymphoblastic lymphoma is a rare aggressive neoplasm of T-/B-precursors resembling acute lymphoblastic leukemia, with no or limited bone marrow involvement (<25%), that develops more frequently in children and young adults and is typically characterized by a grossly enlarged mediastinum, and whose diagnostic hallmark is the expression of a T-/B-precursor cell immunophenotype, the T-cell subset accounting for 90% of all cases. The adoption of pediatric-derived, intensive lymphoblastic leukemia-like protocols led to significantly improved results, with survival rates of about 70% and 90% in adults and children, respectively. Adequate central nervous system prophylaxis and mediastinal irradiation contributed to the therapeutic success; however, the role of radiation therapy is debated due to toxicity concerns and the excellent results obtained with radiation-free programs especially in pediatric patients. With these modern schedules, localized radiotherapy and/or hematopoietic stem cell transplants could be generally omitted, and considered only for high-risk patients identified through postinduction computed tomography/positron-emission tomography scans, minimal residual disease analysis, and new genetics and genomics. New clinical studies will have to confirm the value of these assays for risk-oriented therapy, while further therapeutic progress is expected from the introduction of new drugs and targeting agents.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animales , Biomarcadores , Terapia Combinada , Diagnóstico por Imagen , Descubrimiento de Drogas , Resistencia a Antineoplásicos , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Recurrencia , Factores de Riesgo , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Aberraciones Cromosómicas , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , ARN Mensajero/genética , Adulto , Anciano , Anciano de 80 o más Años , Monitoreo de Drogas , Femenino , Expresión Génica , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Riesgo , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/sangre , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n = 95) or nilotinib (n = 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation.
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About one-half of all Burkitt lymphoma (BL) patients are younger than 40 years, and one-third belong to the adolescent and young adult (AYA) subset, defined by an age between 15 and 25-40 years, based on selection criteria used in different reports. BL is an aggressive B-cell neoplasm displaying highly characteristic clinico-diagnostic features, the biologic hallmark of which is a translocation involving immunoglobulin and c-MYC genes. It presents as sporadic, endemic, or epidemic disease. Endemicity is pathogenetically linked to an imbalance of the immune system which occurs in African children infected by malaria parasites and Epstein-Barr virus, while the epidemic form strictly follows the pattern of infection by HIV. BL shows propensity to extranodal involvement of abdominal organs, bone marrow, and central nervous system, and can cause severe metabolic and renal impairment. Nevertheless, BL is highly responsive to specifically designed short-intensive, rotational multiagent chemotherapy programs, empowered by the anti-CD20 monoclonal antibody rituximab. When carefully applied with appropriate supportive measures, these modern programs achieve a cure rate of approximately 90% in the average AYA patient, irrespective of clinical stage, which is the best result achievable in any aggressive lymphoid malignancy to date. The challenges ahead concern the following: optimization of management in underdeveloped countries, with reduction of diagnostic and referral-for-care intervals, and the applicability of currently curative regimens; the development of lower intensity but equally effective treatments for frail or immunocompromised patients at risk of death by complications; the identification of very high-risk patients through positron-emission tomography and minimal residual disease assays; and the assessment in these and the few refractory/relapsed ones of new monoclonals (ofatumumab, blinatumomab, inotuzumab ozogamicin) and new molecules targeting c-MYC and key proliferative steps of B-cell malignancies.
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The study of minimal residual disease (MRD) in adult patients with acute lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk classification and is the best support for risk-specific therapy with or without allogeneic hematopoietic cell transplantation (HCT). Using case-specific sensitive molecular probes or multiparametric flow cytometry on marrow samples obtained from the end of induction until midconsolidation, MRD assays can detect up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0.01%; ie, ≥104). This cutoff, presently bound to technical limitations and subject to improvement, reflects the individual chemosensitivity and is strongly correlated with treatment outcome. The chance for cure is approximately 70% in the MRD-negative subset but only 20% to 30% in MRD-positive patients, in any diagnostic and risk subset. As shown by prospective trials from Germany, Italy, Spain, and France-Switzerland-Belgium, approximately 50% to 70% of unselected adult patients with Philadelphia-negative ALL achieve and maintain an early MRD response, whereas the remainder do not, including a substantial proportion of clinically standard-risk patients, and require an HCT to avert at least partially the risk of relapse. Along with the diffusion of more effective "pediatric-inspired" chemotherapy programs, the MRD analysis is an integral part of a modern management strategy, guiding the decision process to transplant or not, in which case nonrelapse mortality using HCT in first remission-still 10% to 20%-is totally abolished. The use of new agents such as monoclonal antibodies, small inhibitors, and chimeric antigen receptor T cells is opening a new era of MRD-directed therapies, that will further increase survival rates.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Niño , Supervivencia sin Enfermedad , Humanos , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Factores de RiesgoRESUMEN
INTRODUCTION: Novel targeted therapies and monoclonal antibodies can be combined with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1) before the transplant to reduce tumour burden, 2) as part of the conditioning in place of or in addition to conventional agents 3) after the transplant to allow long-term disease control. Areas covered: This review focuses on the current integration of new drugs with allo-SCT for the treatment of major hematological malignancies for which allo-SCT has been a widely-adopted therapy. Expert opinion: After having been used as single agent salvage treatments in relapsed patients after allo-SCT or in combination with donor lymphocyte infusions, many new drugs have also been safely employed before allo-SCT as a bridge to transplantation or after it as planned consolidation/maintenance. This era of new drugs has opened new important opportunities to 'smartly' combine 'targeted drugs and cell therapies' in new treatment paradigms that may lead to higher cure rates or longer disease control in patients with hematological malignancies.
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Antineoplásicos/uso terapéutico , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inhibidores de Proteínas Quinasas/uso terapéutico , Terapia Recuperativa , Trasplante HomólogoRESUMEN
Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. These treatments, variously targeting CD22, CD20 and CD19 antigens, yield unprecedented high rates of hematologic and molecular remissions even when used in monotherapy and in chemo-resistant or post-transplantation relapsed patients. Beside the encouraging results in relapsed/refractory disease, these agents may open a totally new era in the frontline management of this illness, redefining treatment standards and options for different risk subsets and placing the achievement of a molecular remission at the forefront of treatment objectives. The ever increasing importance of modern immunotherapy in improving treatment design and therapeutic outcome is reviewed.
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Inmunoterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/antagonistas & inhibidores , Terapia Combinada , Terapia Genética , Humanos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Terapia Molecular Dirigida , Estadificación de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismoRESUMEN
The introduction of newer cytotoxic monoclonal antibodies and chimeric antigen receptor modified T cells is opening a new age in the management of B-lineage adult acute lymphoblastic leukemia. This therapeutic change must be very positively acknowledged because of the limits of intensive chemotherapy programs and allogeneic stem cell transplantation. In fact, with these traditional therapeutic tools the cure can be achieved in only 40-50% of the patients. The failure rates are particularly high in the elderly, in patients with post-induction persistence of minimal residual disease and especially in refractory/relapsed disease. The place of the novel immunotherapeutics in improving the outcome of adult patients with B-lineage acute lymphoblastic leukemia is reviewed.
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Following the introduction of targeted therapy with tyrosine kinase inhibitors (TKI) at the beginning of the past decade, the outcome of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) has dramatically improved. Presently, the use of refined programs with first/second generation TKI's and chemotherapy together with allogeneic stem cell transplantation allow up to 50% of all patients to be cured. Further progress is expected with the new TKI ponatinib, overcoming resistance caused by T315I point mutation, other targeted therapies, autologous transplantation in molecularly negative patients, therapeutic monoclonal antibodies like inotuzumab ozogamicin and blinatumomab, and chimeric antigen receptor-modified T cells. Ph+ ALL could become curable in the near future even without allogeneic stem cell transplantation, minimizing the risk of therapy-related death and improving greatly the quality of patients' life.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Edad de Inicio , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Aberraciones Cromosómicas , Ensayos Clínicos como Asunto , Análisis Citogenético , Manejo de la Enfermedad , Resistencia a Antineoplásicos , Drogas en Investigación/uso terapéutico , Predicción , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Trasplante de Células Madre Hematopoyéticas , Humanos , Mesilato de Imatinib , Inmunofenotipificación , Incidencia , Terapia Molecular Dirigida , Piperazinas/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inhibidores de Proteínas Quinasas/clasificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Recurrencia , Resultado del TratamientoRESUMEN
Acute lymphoblastic leukemia (ALL) is curable in about 40-50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates.
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To test the recently developed EUTOS score in predicting optimal response to imatinib and the long-term outcome, 265 patients with early chronic phase chronic myeloid leukaemia treated with standard dose imatinib were analysed. Achievement of optimal response endpoints were higher in low-risk patients, though the difference was not statistically significant: PCyR at 6th month 86% vs 67% (p=0.06), CCyR at 12th month 80% vs 63% (p=0.09), MMR at 18th month 61% vs 36% (p=0.11). However, EUTOS score was predictive for the long-term response. With a median follow-up of 61 months, 53% high-risk patients experienced imatinib failure, compared to 23% in the low-risk group (p=0.013). Among high-risk patients, 4/17 (23%) progressed to accelerated/blastic phase or died, compared to 11/248 (5%) low-risk patients, with 5-year progression-free survival rates of 84±10% and 96±1%, respectively (p=0.04). Our data confirm that EUTOS score envisions the long-term outcome of imatinib therapy.