Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting

Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson  > 0·91, P < 0·001). Multi-centre testing introduced variation in reported LSC percentages but was found to be below the clinical relevant threshold. Clear gating protocols resulted in all laboratories being able to perform LSC assessment of the validation set. Participating centres were nearly unanimously able to distinguish LSChigh (>0·03% LSC) from LSClow (<0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification

Clinical symptoms and chemotherapy completion in elderly patients with newly diagnosed acute leukemia: a retrospective comparison study with a younger cohort

<p>Abstract</p> <p>Background</p> <p>Cancer affects older adults disproportionately. The disease is often difficult to diagnose and treat due to co-morbidities and performance status, and patients tend to discontinue chemotherapy prematurely. There are no systemic studies of the reasons and factors that create a higher withdrawal rate in older acute leukemia patients. This study tried to understand the initial characteristics, blood counts and bone marrow measurements in older acute leukemia patients by comparing them with a younger group to provide information and assistance in early clinical diagnosis, treatment and reasons for treatment withdrawal.</p> <p>Methods</p> <p>Using retrospective medical record reviews, we examined clinical characteristics and chemotherapy completion status in the patients of two groups (age ≥ 60, n = 183 and age <60, n = 183) who were diagnosed with acute leukemia for the first time and were hospitalized in Union Hospital Affiliated with Fujian Medical University from 2004 to 2008.</p> <p>Results</p> <p>There were no statistical differences in initial presenting symptoms of fatigue (67.2% vs. 57.9%, <it>P</it>>0.05) and pallor (53% vs. 59.6%, <it>P</it>>0.05) between the two groups, but older patients demonstrated more underlying diseases including lung infections (25.7%, <it>P </it>= <0.001), cardiovascular disease (4.4%, <it>P </it>= 0.007), and hypertension (20.8%, <it>P </it>=< 0.001). The complete remission rate after chemotherapy (1 to 2 courses) was 49.5% in the older group and 66.7% in the younger group (χ²= 6.202, <it>P </it>= 0.013). The percentage of patients age 60 and older who prematurely discontinued chemotherapy (50.3%), mainly due to the influences of traditional Chinese concept of critical illness, financial difficulties, and intolerance to adverse reactions to chemotherapy, was significantly higher than that of younger patients (37.7%) (χ²= 5.866, <it>P </it>= 0.015).</p> <p>Conclusions</p> <p>A comprehensive approach to diagnosis, treatment selection, and toxicity management, and implementing strategies to enhance treatment compliance may improve outcomes in older adults with acute leukemia.</p

Arterial Embolization Hyperthermia Using As2O3 Nanoparticles in VX2 Carcinoma–Induced Liver Tumors

BACKGROUND: Combination therapy for arterial embolization hyperthermia (AEH) with arsenic trioxide (As(2)O(3)) nanoparticles (ATONs) is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As(2)O(3) nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee. METHODOLOGY/PRINCIPAL FINDINGS: In total, 60 VX(2) liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group) and received AEH with ATONs (Group 1), hepatic arterial embolization with ATONs (Group 2), lipiodol (Group 3), or saline (Group 4), on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C) was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs). Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups. CONCLUSIONS: ATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis