Asunto(s)
Eosinofilia/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Trastornos Mieloproliferativos/tratamiento farmacológico , Proteínas de Fusión Oncogénica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Administración Oral , Eosinofilia/genética , Humanos , Linfoma/genética , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/genética , Inhibidores de Proteínas Quinasas/farmacología , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Metilación/efectos de los fármacos , Neoplasia Residual/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pronóstico , Recurrencia , RiesgoAsunto(s)
Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/genética , Tirosina Quinasa 3 Similar a fms/genética , Adulto , Anciano , Anciano de 80 o más Años , ADN (Citosina-5-)-Metiltransferasas/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Proteínas Nucleares/genética , Secuencias Repetidas en Tándem/genética , Adulto JovenRESUMEN
This corrects the article DOI: 10.1038/leu.2016.303.
RESUMEN
Most clinical trials exclude patients with poor performance or comorbidities. To study whether patients with these characteristics can be treated within a clinical trial, we conducted a study for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction or comorbidities. Primary endpoint was 60-day survival. Study included stopping rules for survival and response. Treatment consisted on a combination of azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were enrolled. Median follow-up was 7.4 months (0.3-29). Sixty-day survival was 83%. No stopping rules were met. Main adverse events (AEs) were grades 1 and 2 gastrointestinal toxicities. In view of these results, we expanded the study and treated 79 additional patients: 27 with azacitidine (AZA) and 52 with azacitidine and vorinostat (AZA+V). Median follow-up was 22.7 months (12.6-47.5). Sixty-day survival rate was 79% (AZA=67%, AZA+V=85%, P=0.07). Median overall survival was 7.6 months (4.5-10.7). Median event-free survival was 4.5 months (3.5-5.6). Main AEs included grades 1 and 2 gastrointestinal toxicities. Our results suggest this subset of patients can be safely treated within clinical trials and derive clinical benefit. Relaxation of standard exclusion criteria may increase the pool of patients likely to benefit from therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores , Médula Ósea/patología , Aberraciones Cromosómicas , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Resultado del TratamientoRESUMEN
Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27-89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) <1 year (N=28, 25%); group 2: relapsed/refractory AML with CRD ⩾1 year (N=5, 5%); group 3: untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome (MDS) or untreated myelofibrosis (MF; N=57, 52%); and group 4: AML evolving from MDS or relapsed/refractory MDS or MF (N=20, 18%). Treatment consisted of decitabine 20 mg/m(2) daily for 5 days and GO 3 mg/m(2) on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.
Asunto(s)
Aminoglicósidos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Azacitidina/análogos & derivados , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Aminoglicósidos/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Azacitidina/administración & dosificación , Azacitidina/efectos adversos , Decitabina , Femenino , Gemtuzumab , Humanos , Masculino , Persona de Mediana Edad , Lectina 3 Similar a Ig de Unión al Ácido Siálico/análisisAsunto(s)
Biomarcadores de Tumor/genética , Isocitrato Deshidrogenasa/genética , Mutación/genética , Síndromes Mielodisplásicos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: The clinical phenotype of patients with myeloproliferative neoplasms (MPNs) including primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET) whom manifest WHO grade 1 marrow fibrosis is poorly defined. Current IWG-MRT criteria require 2+ marrow fibrosis for diagnosis of post PV/ET myelofibrosis (MF). In contrast, the 2008 WHO definition of PMF does not require a minimum fibrosis threshold. METHODS: We retrospectively analyzed the clinical characteristics of 91 MPN patients with 1+ marrow fibrosis. We compared the clinical phenotype of sub threshold fibrosis PV/ET with that manifested by PMF. We applied the IWG-MRT criteria for post-PV/ET MF with the fibrosis component omitted and evaluated for percentage of criteria fulfillment. RESULTS: When IWG-MRT criteria were applied to the PV/ET group, 38/58 (66%) of patients fulfilled criteria for diagnosis of post-PV/ET myelofibrosis except for the 2+ fibrosis requirement. Comparison of sub threshold fibrotic PV/ET clinical phenotype to PMF revealed similar characteristics including heavy symptomatic burden (57% and 52%), presence of splenomegaly (43% and 55%), leukoerythroblastic blood smear (38% and 45%), and median hemoglobin (12.8g/dL and 11.1g/dL). CONCLUSION: MPN progression represents a biological spectrum and definitions of progression in ET/PV may benefit from criteria not restricted by degree of fibrosis.
Asunto(s)
Policitemia Vera/diagnóstico , Trombocitemia Esencial/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Policitemia Vera/patología , Trombocitemia Esencial/patologíaAsunto(s)
Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Anciano , Femenino , Humanos , Janus Quinasa 2/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Enfermedades Mielodisplásicas-Mieloproliferativas/tratamiento farmacológico , Enfermedades Mielodisplásicas-Mieloproliferativas/mortalidad , Enfermedades Mielodisplásicas-Mieloproliferativas/patología , PronósticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Arabinonucleósidos/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Arabinonucleósidos/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Humanos , Persona de Mediana Edad , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Vincristina/administración & dosificación , Vincristina/efectos adversosAsunto(s)
Transformación Celular Neoplásica/patología , GTP Fosfohidrolasas/genética , Leucemia Mieloide Aguda/genética , Proteínas de la Membrana/genética , Mutación/genética , Síndromes Mielodisplásicos/genética , Proteínas Proto-Oncogénicas/genética , Tirosina Quinasa 3 Similar a fms/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Pronóstico , Proteínas Proto-Oncogénicas p21(ras) , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Homoharringtonine is an alkaloid inhibitor of protein synthesis with activity in myeloid malignancies. We report a phase II pilot study of homoharringtonine in myelodysplastic syndrome (MDS). Induction consisted of homoharringtonine at 2.5 mg/m(2) via continuous infusion for 7 days. Maintenance was given every 4 weeks. Nine patients were enrolled: five with refractory anaemia with excess blasts, two with refractory anaemia with excess blasts in transformation, one each with refractory anaemia and chronic myelomonocytic leukaemia respectively. Median age was 70 years (55-84) and 6 (66%) were male. Per International Prognostic Scoring System (IPSS) two patients were intermediate-1, five intermediate-2 and two high-risk. Median chemotherapy courses were one (1-3). One patient (11%) responded with complete haematological and cytogenetic remission after one course. Eight patients did not respond (four had stable disease, two progressed to acute leukaemia and two died during induction - from aspergillus pneumonia and intracerebral haemorrhage respectively). Grade 3/4 myelosuppression seen in 56% (5/9). Serious non-haematological toxicities included one case of grade 4 left bundle branch heart block and one grade 3 nephrotoxicity. Median time between courses was 42 days (35-72 days). In conclusion homoharringtonine might have clinical activity in some patients with MDS.
Asunto(s)
Harringtoninas/administración & dosificación , Hematínicos/administración & dosificación , Síndromes Mielodisplásicos/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Femenino , Harringtoninas/efectos adversos , Hematínicos/efectos adversos , Homoharringtonina , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
The clinical features and outcomes of 148 patients with acute myeloid leukemia (AML) and 11q23 chromosomal abnormalities were compared with those of 2640 patients with non-11q23 AML. Patients with t(9;11) ), t(6;11) or other 11q23 balanced translocations (t(11;v)(q23;v)) presented at a younger age and with higher percentage of bone marrow blasts. Unbalanced 11q23 abnormalities were commonly associated with deletions of chromosomes 5q, 7q and/or complex karyotypes. In multivariate analysis, when compared with patients with non-11q23 AML and unfavorable-risk karyotype, there was a significant difference in overall survival (OS) for patients with t(9;11) (P=0.004), whereas there were no differences in OS for patients with t(6;11) (P=0.62), t(11;19) (P=0.20) and unbalanced 11q23 aberrations (P=0.85) or t(11;v)(q23;v) (P=0.59), indicating that t(9;11) has an independent intermediate prognostic significance, with all others being poor prognostic factors for OS; this was further confirmed by comparing them with patients with non-11q23 AML and intermediate-risk karyotype. Using intention-to treat analysis based on donor availability, we also noted that allogeneic stem cell transplant in first remission had a significant benefit toward improving OS (P<0.001) and relapse-free survival (P<0.001) in patients with AML and 11q23 abnormalities.
Asunto(s)
Cromosomas Humanos Par 11 , Leucemia Mieloide Aguda/genética , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Translocación Genética , Trasplante Homólogo , Adulto JovenRESUMEN
Liver malformations including lobe and segmental abnormalities are rare. We report a 65-year-old lady with complaints of breathlessness and fullness after meals for two months. Investigations revealed a diaphragmatic hernia on the right side with a bifid liver; the right lobe of the liver was among the hernia contents. The lady is asymptomatic after surgical repair.