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Cancer ; 127(22): 4213-4220, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34343352


BACKGROUND: Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. Although lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare with intensive chemotherapy (IC) for R/R AML. METHODS: Outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN) were compared with IC-based regimens including idarubicin with cytarabine, with or without cladribine, clofarabine, or fludarabine, with or without additional agents. Propensity scores derived from patient baseline characteristics were used to match DEC10-VEN and IC patients to minimize bias. RESULTS: Sixty-five patients in the DEC10-VEN cohort were matched to 130 IC recipients. The median ages for the DEC10-VEN and IC groups were 64 and 58 years, respectively, and baseline characteristics were balanced between the 2 cohorts. DEC10-VEN conferred significantly higher responses compared with IC including higher overall response rate (60% vs 36%; odds ratio [OR], 3.28; P < .001), complete remission with incomplete hematologic recovery (CRi, 19% vs 6%; OR, 3.56; P = .012), minimal residual disease negativity by flow cytometry (28% vs 13%; OR, 2.48; P = .017), and lower rates of refractory disease. DEC10-VEN led to significantly longer median event-free survival compared with IC (5.7 vs 1.5 months; hazard ratio [HR], 0.46; 95% CI, 0.30-0.70; P < .001), as well as median overall survival (OS; 6.8 vs 4.7 months; HR, 0.56; 95% CI, 0.37-0.86; P = .008). DEC10-VEN was independently associated with improved OS compared with IC in multivariate analysis. Exploratory analysis for OS in 27 subgroups showed that DEC10-VEN was comparable with IC as salvage therapy for R/R AML. CONCLUSION: DEC10-VEN represents an appropriate salvage therapy and may offer better responses and survival compared with IC in adults with R/R AML.

Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes , Citarabina , Decitabina , Humanos , Pontuação de Propensão , Sulfonamidas
Haematologica ; 102(10): 1709-1717, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28729302


Vosaroxin is an anti-cancer quinolone-derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥60 years of age with newly diagnosed acute myeloid leukemia (n=58) or myelodysplastic syndrome (≥10% blasts) (n=7) in a phase II non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m2 on days 1 and 4 with decitabine 20 mg/m2 on days 1-5 every 4-6 weeks for up to seven cycles. Due to a high incidence of mucositis the subsequent 43 patients were given vosaroxin 70 mg/m2 on days 1 and 4. These 65 patients, with a median age of 69 years (range, 60-78), some of whom with secondary leukemia (22%), adverse karyotype (35%), or TP53 mutation (20%), are evaluable. The overall response rate was 74% including complete remission in 31 (48%), complete remission with incomplete platelet recovery in 11 (17%), and complete remission with incomplete count recovery in six (9%). The median number of cycles to response was one (range, 1-4). Grade 3/4 mucositis was noted in 17% of all patients. The 70 mg/m2 induction dose of vosaroxin was associated with similar rates of overall response (74% versus 73%) and complete remission (51% versus 41%, P=0.44), reduced incidence of mucositis (30% versus 59%, P=0.02), reduced 8-week mortality (9% versus 23%; P=0.14), and improved median overall survival (14.6 months versus 5.5 months, P=0.007). Minimal residual disease-negative status by multiparametric flow-cytometry at response (± 3 months) was achieved in 21 of 39 (54%) evaluable responders and was associated with better median overall survival (34.0 months versus 8.3 months, P=0.023). In conclusion, the combination of vosaroxin with decitabine is effective and well tolerated at a dose of 70 mg/m2 and warrants randomized prospective evaluation. NCT01893320.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/análogos & derivados , Biomarcadores , Decitabina , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Naftiridinas/administração & dosagem , Neoplasia Residual , Indução de Remissão , Análise de Sobrevida , Tiazóis/administração & dosagem , Resultado do Tratamento
SSM Popul Health ; 3: 411-418, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29349234


In the United States, associations between attained education and adult health typically are larger for those from disadvantaged childhood backgrounds. However, it remains unclear how specific key childhood indicators contribute to these adult health patterns, especially outside the United States. Drawing on the 2014 European Social Survey (20 countries; N=31544), we investigate the key childhood and adolescent indicators of parental education, childhood financial strain, and any serious household conflict growing up, given how these early exposures are known to correlate strongly with both educational attainment and adult health. In regressions with country fixed effects, we find across Europe that higher levels of education are more strongly linked to lessened adult depressive symptoms when childhood disadvantage is present in terms of lower levels of parental education or higher childhood financial strain specifically. However, adjusted predictions reveal that childhood financial strain contributes to this heterogeneity in educational returns far more strongly than parental education. For self-rated health, only childhood financial strain enhances estimated educational health benefits when considering all key childhood social and economic factors jointly. Similarly, childhood financial strain in particular enhances educational protection against overall rates of disease in adulthood. Overall, our findings support prior work on United States data revealing higher educational health returns given childhood disadvantage. At the same time, our findings across three distinct adult health indicators suggest the particular importance of childhood financial strain to understanding heterogeneity in educational health returns.

West Indian med. j ; 49(suppl.4): 21-2, Nov. 9, 2000.
Artigo em Inglês | MedCarib, MedCarib | ID: med-380


OBJECTIVE: Bicycle spoke injuries represent a peculiar pattern of injury sustained when a child's foot becomes trapped in the spokes of a bicycle. The aim of this study was to higlight the types of injuries sustained and their associated morbidity. METHODS: A retrospective review was made of all children who had sustained a bicycle spoke injury between 1997 and 1999 and who had been admitted to the Bustamante Hospital for Children. Sixty cases were identified but thirteen were excluded, leaving 47 for analysis. Demographic details of each child, along with relevant clinical data, were retrieved. Where indicated, radiographs were reviewed and the data were analysed using the SPSS statistical package. RESULTS: There were 26 males and 21 females (mean age 5 years ñ 22.2 SD; age range 2-10 years). Sixty-four per cent were aged 0-5 years. The mean time to presentation was 4.4 days, although most patients were from the Corporate Area. The commonest injuries (74 percent) were abrasions of varying depths along with lacerations and friction burns. The lateral and medial aspects of the ankle were injured most often (62 percent). Six cases (13 percent) had fractures. Antibotics were required in 77 percent of cases and surgery in 30 percent. Hospitalisation was for a mean of 9 (SD ñ 9.3) days. Time to healing of the soft tissue wounds was a mean of 17 (SD ñ 24.4) days. Two children (4.3 percent) had permanent residual deformities. CONCLUSION: Bicycle spoke injuries caused significant morbidity to the study children. Adequate parental supervision of children on bicylces, along with the recognition that these are not trivial injuries, would go a long way in reducing the associated morbidity.(Au)

Criança , Humanos , Feminino , Masculino , Pré-Escolar , Traumatismos do Pé/complicações , Morbidade/tendências , Jamaica , Estudos Retrospectivos , Traumatismos do Tornozelo/diagnóstico