Hypocellular acute myeloid leukemia in adults: analysis of the clinical outcome of 123 patients

Background

The hypocellular variant of acute myeloid leukemia accounts for less than 10% of all cases of adult acute myeloid leukemia. It is defined by having less than 20 percent of cellular bone marrow in a biopsy at presentation. It is unclear in the literature whether the outcome of hypocellular acute myeloid leukemia differs from that of non-hypocellular acute myeloid leukemia.

Design and Methods

We retrospectively analyzed all the cases reported to be hypocellular acute myeloid leukemia between 2000 and 2009. A second pathology review was conducted and the diagnosis was confirmed in all cases.

Results

One hundred twenty-three (9%) patients were identified: patients with hypocellular acute myeloid leukemia were older than those with non-hypocellular acute myeloid leukemia (P=0.009) and more frequently presented with cytopenias (P<0.001). Forty-one patients with hypocellular acute myeloid leukemia had an antecedent hematologic disorder and 11 patients had received prior chemo-radiotherapy for non-hematopoietic neoplasms. On multivariate analysis, overall survival, remission duration and event-free survival were comparable to those of other patients with acute myeloid leukemia.

Conclusions

The outcome of hypocellular acute myeloid leukemia does not differ from that of non-hypocellular acute myeloid leukemia.     

Age-related clinical characteristics and prognosis in non-senile adults with acute myeloid leukemia

<正>Objective To explore age-related clinical characteristics,early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at     

Correlation between CD34 expression and chromosomal abnormalities but not clinical outcome in acute myeloid leukemia

The hemopoletic stem cell marker CD34 has been reported to be a useful predictor of treatment outcome in acute myeloid leukemia (AML). Previous data suggested that CD34 expression may be associated with other poor prognosis factors in AML such as undifferentiated leukemia, secondary AML (SAML), and clonal abnormalities involving chromosome 5 and 7. In order to analyze the correlations between the clinicopathologic features, cytogenetic and CD34 expression in AML, we retrospectively investigated 99 patients with newly diagnosed AML: 85 with de novo disease and 14 with secondary AML (SAML). Eighty-six patients who received the same induction chemotherapy were available for clinical outcome. Defining a case as positive when ≥ 20% of bone marrow cells collected at diagnosis expressed the CD34 antigen, forty-five patients were included in the CD34 positive group. Ninety patients had adequate cytogenetic analysis. Thirty-two patients (72%) with CD34 positive AML exhibited an abnormal karyotype whereas 15 patients (28%) with CD34 negative AML had abnormal metaphases (P < 0.01). Monosomy 7/7q- or monosomy 5/5q- occurred in 10 patients and 8 of them expressed the CD34 antigen (P < 0.05). All patients with t(8;21) which is considered as a favorable factor in AML had levels of CD34 ≥ 20% (P < 0.05). We did not find any association between CD34 expression and attainment of complete remission, overall survival, or disease-free survival. In conclusion, the variations of CD34 expression in AML are correlated with cytogenetic abnormalities associated both with poor and favorable outcome. The evaluation of the correlations between CD34 antigen and clinical outcome in AML should take into account the results of pretreatment karyotype. © 1996 Wiley-Liss, Inc.     

CD56 and PGP expression in acute myeloid leukemia: impact on clinical outcome

BACKGROUND AND OBJECTIVES: Overexpression of P-glycoprotein (PGP), a multidrug-related (MDR) protein, is one of the most important factors responsible for reduced drug sensitivity in acute myeloid leukemia (AML). Recently, we demonstrated that the presence of CD56 antigen, an isoform of the neural adhesion molecule, in AML cells is a negative independent prognostic factor for the achievement of complete remission (CR) and correlates with shorter survival. Since in our previous report we observed a more frequent PGP expression in CD56+ patients, we hypothesized that the reduced response to chemotherapy in this group of patients was due to increased PGP-mediated drug efflux. To confirm this hypothesis in this study PGP and CD56 expression on AML cells was correlated with other clinical and biological features and treatment response. DESIGN AND METHODS: Immunophenotypic analysis, including evaluation of CD56 and PGP expression, was performed using multiparameter flow cytometry on fresh and/or cryopreserved blast cells, obtained after informed consent, from bone marrow and/or peripheral blood of 143 consecutive newly diagnosed AML cases at the time of diagnosis. Samples expressing CD56 in at least 15% or more cells were considered as positive (CD56+). PGP expression was expressed as a mean fluorescence index (MFI) i.e. as the ratio of sample mean fluorescence channel and the isotypic control mean fluorescence channel. RESULTS: Overall results showed that 67/143 cases were PGP-/CD56-, 23/143 were PGP+ /CD56+, 40/143 were PGP+/CD56- and the remaining 13/143 were PGP-/CD56+. CD56+ and PGP+ on AML cells significantly reduced the CR rate (83% in the PGP-/CD56- group vs 60% in the PGP-/CD56+ group, 46% in the PGP+/CD56- group and 58% in the PGP+/CD56+ group, p = 0.002). In addition we observed a significantly higher proportion of total failures in patients expressing PGP or CD56 compared to in the group not expressing either (73% vs 27%, respectively; p = 0.0001). CD56 and PGP overexpression influenced the overall survival: in fact, the median survival of CD56+ and PGP+ patients ranged from 10 to 23 months, while the actuarial survival of CD56-/PGP- patients at 5 years is 52% (p = 0.023). INTERPRETATION AND CONCLUSIONS: Our data underline the independent negative prognostic role of PGP and CD56 expression in acute myeloid leukemia. Since the mechanism by which CD56 reduces drug sensitivity is still unknown, further investigations are required.     

Allo-HSCT for acute myeloid leukemia with myelodysplastic-related changes: a clinical analysis

<正>Objective To evaluate the outcomes and prognostic factors of adults with acute myeloid leukemia with myelodysplastic-related changes( AML-MRC) who received allogeneic hematopoietic stem cell transplantation( alloHSCT).The genetic mutation lineage of patients with AML-MRC and the molecular mutation affecting the transplantation prognosis was discussed.     

Predictors of infarct size after primary coronary angioplasty in acute myocardial infarction from pooled analysis from four contemporary trials

Determinates of infarct size in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have been incompletely characterized, in part because of the limited sample size of previous studies. Databases therefore were pooled from 4 contemporary trials of primary or rescue PCI (EMERALD, COOL-MI, AMIHOT, and ICE-IT), in which the primary end point was infarct size assessed using technetium-99m sestamibi single-photon emission computed tomographic imaging, measured at the same core laboratory. Of 1,355 patients, infarct size was determined using technetium-99m sestamibi imaging in 1,199 patients (88.5%), at a mean time of 23 +/- 15 days. Median infarct size of the study population was 10% (interquartile range 0% to 23%; mean 14.9 +/- 16.1%). Using multiple linear regression analysis of 18 variables, left anterior descending infarct artery, baseline Thrombolysis In Myocardial Infarction grade 0/1 flow, male gender, and prolonged door-to-balloon time were powerful independent predictors of infarct size (all p <0.0001). Other independent correlates of infarct size were final Thrombolysis In Myocardial Infarction grade <3 flow (p = 0.0001), previous AMI (p = 0.005), symptom-onset-to-door time (p = 0.021), and rescue angioplasty (p = 0.026). In conclusion, anterior infarction, time to reperfusion, epicardial infarct artery patency before and after reperfusion, male gender, previous AMI, and failed thrombolytic therapy were important predictors of infarct size after angioplasty in patients with AMI assessed using technetium-99m sestamibi imaging and should be considered when planning future trials of investigational drugs or devices designed to enhance myocardial recovery.     

Treatment of relapsed and refractory acute myeloid leukemia with diaziquone and mitoxantrone: a CALGB phase I study

Twenty-one patients with relapsed or refractory acute myeloid leukemia (AML) were treated with mitoxantrone (12 mg/m2/day, days 1-3) and diaziquone (continuous infusion days 1-5). The dosage of diaziquone was increased for sequential cohorts of seven patients from 20 mg/m2/day to 24 mg/m2/day, and finally to 28 mg/m2/day to determine the maximum tolerated dose for this chemotherapy combination. Myelosuppression was the dose-limiting toxicity. The median time to recovery of blood counts was greater at the highest dose of diaziquone (48 days) than at the lower two doses (31 and 28 days). Other toxic effects were minimal. Overall, 9/21 (43%, 95% confidence interval, 0.22 to 0.66) patients achieved complete remission. We conclude that this combination of drugs shows sufficient antileukemic activity with acceptable toxicity to warrant further trials.     

Important factors improving outcome of young adults with acute lymphoblastic leukemia (ALL)

Four categories of important factors improving outcome of young adults and older adolescents with acute lymphoblastic leukemia (ALL) are biologic type, clinical trials, pediatric vs. adult treatment regimen, and psychosocial challenges. Overall, the outcome of ALL in the age group has improved and beginning to catch up with that in children, as exemplified by CALGB 10403, a pediatric treatment regimen. Each is dependent for optimum development, however, on progress in the others. Without adequate psychosocial support and improvement, progress in clinical trials, translational research, and pediatric regimen application is impaired. Without clinical trials, advances in translational research, optimal pediatric regimen application and adequate psychosocial research are restricted. Overall, we have improved the outcome and outlook of ALL in AYAs, as exemplified by CALGB 10403, but we and our current and future patients still have a long way to go.     

Cardiovascular outcome trials in obesity: A review

Obesity is a global epidemic associated with over 200 health complications and a significant risk of developing cardiovascular disease (CVD), partly by increasing classical risk factors such as lipid and glucose levels and blood pressure. Weight loss through lifestyle interventions, pharmacotherapy and/or bariatric surgery improves CV risk factors. Cardiovascular outcome trials (CVOTs) of anti‐obesity medications aim to evaluate the CV safety and benefits of pharmacotherapy. Many CVOTs in obesity have either failed to demonstrate a CV benefit or have been terminated prematurely because of safety issues, prompting regulatory agencies to define new requirements (based on those for CVOTs in type 2 diabetes [T2D]). CVOTs of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in T2D have demonstrated that some GLP‐1RAs reduce CV risk and may help inform future CVOTs in obesity, given the approval of liraglutide 3.0 mg for obesity. In this review, the evidence for the link between obesity and CVD is considered in the context of studies showing that weight loss improves markers of CV risk and risk of adverse CV events. The review also examines the CVOTs in obesity that have been conducted to date and those under way, such as the SELECT trial with subcutaneous semaglutide of 2.4 mg.     

Improved clinical outcome of acute myeloid leukemia with FLT3-ITD mutation treated with sorafenib

<正>Objective To analyze the efficacy of sorafenib on the treatment of patients diagnosed as acute myeloid leukemia(AML)with FLT3-ITD mutation.Methods From January 2012 to February 2015,42 cases of AML with FLT3-ITD mutation according to MICM(morphology,immunology,cytogenetics and molecular)diagnosis system in our hospital were retrospectively analyzed.Thirty-two     

A heavy metal baseline score predicts outcome in acute myeloid leukemia

Despite abundant epidemiological data linking metals to leukemia and other cancers, baseline values of toxic and essential metals in patients with leukemia and the clinical impact of these metals remain unknown. Thus, we sought to quantify metal values in untreated patients with acute myeloid leukemia (AML) and controls and determine the impact of metal values on AML patients' survival. Serum samples from patients with untreated AML and controls at Hospices Civils de Lyon were analyzed and compared for trace metals and copper isotopic abundance ratios with inductively coupled plasma mass spectrometry. Survival analysis was performed as a function of metal values, and a multi-metal score was developed for patients with AML. Serum samples were collected from 67 patients with untreated AML and 94 controls. Most patients had intermediate-risk cytogenetics (63.1%) without FLT3 internal tandem duplication mutations (75.6%) or NPM1 mutations (68.1%). Most metal values differed significantly between AML and control groups. Patients with lower magnesium and higher cadmium values had the worst survival rates, with only 36% surviving at 6 months (P = .001). The adverse prognostic effect of this combination was maintained on multivariate analysis. Based on this, we developed a novel metal score, which accounts for multiple relative abnormalities in the values of five toxic and five essential metals. Patients with a higher metal score had significantly worse survival, which was maintained on multivariate analysis (P = .03). This baseline metal scoring system was also prognostic when we applied it to a separate population of front-line AML patients.     

P-glycoprotein expression in adult acute myeloid leukemia: correlation with induction treatment outcome

Drug resistance has become a major cause of the treatment failure in patients with acute leukemia. P-glycoprotein (P-gp), which is associated with multidrug resistance (MDR) phenotype, has been reported to be an important predictor of the treatment outcome. The aim of this study was to analyze the value of P-gp expression in bone marrow cells as a predictor of the response to remission induction chemotherapy, as well as duration of remission in adult patients with newly diagnosed acute myeloid leukemia (AML). We examined the expression of P-gp in 31 patients using the monoclonal antibody UIC2. Direct immunofluorescent labeling was performed and samples were analyzed by flow cytomery. Kolmogorov-Smirnov test (D-value) was used to estimate UIC2 staining. A D > or = 0.3 for labeling of gated leukaemic blasts as compared to that of the isotypic control was defined positive (+) and compared to clinical data. P-gp expression was found in 14/31 (45.6%) patients, 17/31 (54.8%) of the samples were found P-gp negative(-). No correlation was found regarding age, sex and FAB subtype, altough 6/14 (43%) cases with more than 50% of cells having P-gp expression, were CD34+/CD7+. Complete remission rates were significantly lower in UIC2+ patients than in UIC2- cases (70% vs 35%, p < 0.01). Complete remission duration was also shorter in UIC2+ patients (6 vs 12.4 months). Our data indicate, that P-gp expression is a reliable marker of resistance to induction treatment in patients with de novo AML and can help to identify patients who may require alternative regimens designed to overcome therapy resistance.     

Drug-eluting stents in the treatment of intermediate lesions: pooled analysis from four randomized trials.

OBJECTIVES: To address the safety and efficacy of drug-eluting stents (DES) in the treatment of intermediate lesions, we performed a pooled analysis of four randomized DES versus bare-metal stent (BMS) trials and assessed outcomes among patients with intermediate lesions. BACKGROUND: Before the introduction of DES, intermediate coronary lesions were commonly managed based on physiologic or anatomic assessment of lesion severity. The DES may challenge this paradigm. METHODS: The study population involved 167 of 2,478 randomized patients (6.7%) with intermediate lesions (diameter stenosis <50% [mean 44%] by quantitative coronary angiography) from the Sirolimus-coated Bx Velocity Balloon Expandable Stent in the Treatment of Patients with De Novo Coronary Artery Lesions (SIRIUS), TAXUS-IV, and the First and Second First Use to Underscore Restenosis Reduction with Everolimus (FUTURE-I and -II) trials. End points examined included early (in-hospital and 30-day) and late (1-year) major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis, and follow-up angiographic restenosis. RESULTS: Patients with intermediate lesions randomized to DES versus BMS had low rates of 30-day MACE (1.1% vs. 4.0% respectively; p = 0.22). At one-year follow-up, patients treated with DES versus BMS had similar rates of cardiac death (0% vs. 2.7%, respectively; p = 0.11) and MI (3.4% vs. 5.4%; p = 0.49) but markedly lower rates of TVR (3.4% vs. 20.3%; p = 0.0004), MACE (5.6% vs. 25.4%; p = 0.0003), and binary angiographic restenosis (1.8% vs. 34.0%; p < 0.0001). No patient in either group developed stent thrombosis. CONCLUSIONS: Compared with BMS, treatment of intermediate lesions with DES appears safe and results in a marked reduction in clinical and angiographic restenosis. The efficacy of DES may require a reevaluation of current treatment paradigms for intermediate lesions.