Megestrol acetate therapy is a powerful appetite stimulant which led to weight gain, composed of both fat mass and fat-free mass. Megestrol acetate is well tolerated, with few and mild side-effects. If megestrol acetate therapy is started at the onset of anorexia, the use of more expensive, invasive and complicated techniques of nutritional support may be avoided.
Adhesive capsulitis affecting shoulders has been extensively studied by orthopedic surgeons, but few reports have been published on this condition when it affects other joints (hips, ankles). To our knowledge no pediatric cases have been reported. As its treatment requires prolonged physiotherapy and sometimes manipulation, a correct diagnosis is essential. We would like to emphasize the importance of having this condition in mind when one is regarding a differential diagnosis, also in children.
Primary refractory or relapsed acute myeloid or lymphoid leukemia are characterized by unsatisfactory response to current therapy and short survival. The therapeutic approach consists on salvage chemotherapy treatment followed by allogenic hematopoietic stem-cell transplantation (HSCT). FLAG (Fludarabine, Cytarabine and G-CSF) is an effective salvage therapy in this setting. The regimen is designed with intravenous (IV) Fludarabine. In a period of time there was no IV Fludarabine available in our Country, only an oral presentation. There are some bioequivalence studies of oral and IV Fludarabine, mostly in chronic lymphocytic leukemia/low grade lymphomas. Based of these studies we treated patients with FLAG with the equivalent dose of oral Fludarabine (dose 40 mg/m2 day). This is a comparative retrospective study of efficacy and toxicity of FLAG with oral and IV Fludarabine. Forty-four patients with relapsed or refractory acute leukemia were treated with FLAG between 2005 and 2013. The diagnoses were: Pre-B ALL (63.3%), AML (31.8%), APL (2.3%) and T-ALL (2.3%). The median age was 26.7 years and 63.6% were early relapses, 20.5% primary refractory and 15.9% late relapses. In 59.1% of the cases FLAG was the second line of treatment and in 40.9% it was the third or forth line. Twenty-one patients (47.7%) were treated with oral Fludarabine and 23 patients (52.3%) with IV Fludarabine. There were no differences between both groups. Results: Complete remission (CR) rate was 31.8% (33.3% for AML and 31% for ALL), 23.8% with oral Fludarabine and 39.1% with IV Fludarabine (P=0.342). Median overall survival (OS) was 8.07 months: 6.14 months with oral Fludarabine and 10.78 months with IV Fludarabine (P=0.363). There was a higher incidence of neutropenic fever with IV Fludarabine than with oral Fludarabine (100% vs. 76.2%, P= 0.019) as well as higher incidence of septic shock (34.8% vs. 0%, P=0.003) and a longer hospitalization (26.8 vs. 19.4 days, P=0.046). On univariate analysis, the factors associated with shorter overall survival were: number of lines of treatment (more than 1 previous to FLAG) (HR: 2.03, CI 95% 1.09-3.78; P=0.03) and septic shock (HR: 2.8, CI 95% 1.24-6.36; P=0.023). Factors associated with a higher survival were: CR with FLAG (HR: 0.26, CI 95% 0.12-0.58; P<0.001) and HSCT (HR: 0.15, CI 95% 0.02-1; P= 0.009). On multivariate analysis, factors that remained significant were number of lines of treatment (HR: 2.5, CI 95% 1.26-4.99; P= 0.009), septic shock (HR: 3.93, CI 95% 1.67-9.25; P=0.002) and CR with FLAG (HR: 0.18, CI 95% 0.08-0.44; P<0.001). There is a non significant tendency of better CR rates and OS with IV Fludarabine. There is a significative difference in toxicity with higher rates of neutropenic fever, septic shock and a longer hospitalization. Oral Fludarabine is effective for salvage treatment of primary refractory or relapsed acute lymphoid or myeloid leukemia. As far as we know there are no previous reports of oral fludarabine-containing FLAG in acute leukemia patients. The optimal dose needs to be determined. The prognosis is this group of patients is very poor and the responses are only transitory. Salvage chemotherapy should be used only as a bridge for HSCT. Disclosures No relevant conflicts of interest to declare.
Background:In the last decades, the outcome of patients with AML treated with intensive chemotherapy have improved, reaching long‐term overall survival (OS) >40%. This has been due to better supportive care and risk stratification with cytogenetic/molecular tests, increasingly access to transplant (HSCT) programs and more recently, new drugs. This improvement has not been equivalent in developing countries were the OS is lower. There are no multicentric studies with survival analysis in Mexico.Aims:To analyze the outcome of Mexican adult patients with AML treated with intensive chemotherapy.Methods:Multicentric and retrospective study, including patients with AML diagnosed between January 2013 and December 2017 in 13 centers in Mexico.Results:The information of 525 patients with AML with a median age of 47 years was recorded. Cytogenetics were available in 363/525 patients (69.1%). The patients were classified according to cytogenetic risk: favorable 16.0%, intermediate 55.6% and unfavorable 28.4%. FLT3 mutations were analyzed in 64 cases and positive in 22% and NPM1 mutations in 43 cases and positive in 12%. Other mutations were analyzed less frequently. The majority of the patients (80.2%) were treated with intensive chemotherapy. When comparing them with those receiving non‐intensive regimens, they were younger (43 vs. 70 years, p < 0.001), with less comorbidity (HCT‐CI≥ 3 11.2% vs. 32.7%, p < 0.001) and fewer secondary AML (10.5% vs. 26.9%, p < 0.001). The most common induction regimen was 7+3 in 74.1%. The complete remission (CR) rate was 71.3%. Induction related mortality occurred in 17.8% and we identify as independent risk factors: >60 years (OR=2.088), ECOG>2 (OR=4.820), prior solid tumor (OR=3.795) and active infection (OR=1.817). Some patients (28.9%) received maintenance therapy after consolidation: methotrexate and 6‐mercaptopurine (66.3%), cytarabine‐based (27.7%) or hypometilating agents (6%). Allogeneic HSCT was performed in 33 patients (8.2%) in first CR.The 3‐year overall survival (OS) was 34.8% (median OS of 13.9 months). Cytogenetic risk was significantly associated with survival, with median OS of 45.2, 20.5 and 12 months for favorable, intermediate and unfavorable cytogenetics (p = 0.001). Survival increased in patients with less comorbidities (16.6 vs. 8 months, p = 0.001) and in those who received allogenic HSCT in first remission (median NR vs. 10.6 months, p < 0.01). Interestingly, during remission, any maintenance therapy had a positive trend in survival compared to those with no maintenance: median NR vs. 27.1 months, p = 0.011; nevertheless, this advantage was only significant for patients receiving cytarabine‐based maintenance (p = 0.021) and for intermediate cytogenetic risk (p = 0.017). In a multivariate analysis, prognostic factors related to worse OS were secondary AML (HR=2.029) and high cytogenetic risk (HR=1.874), whereas maintenance therapy (HR=0.547) and allogeneic HSCT (HR=0.034) were associated with better OS.Summary/Conclusion:This is the first large multicentric report that analyses the outcome of adult AML patients in Mexico. The impact of cytogenetic risk on survival was like previous reports. The use of a cytarabine‐based maintenance is associated with better survival only in intermediate‐risk patients. We identified some short‐term challenges: to standardize supportive care in order to reduce induction‐related mortality and to expand access to cytogenetic/molecular testing and HSCT programs. This will be addressed in a prospective multicentric trial.image
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