Yearly Budgetary Impact (Model Estimated Outputs).

<p>Yearly Budgetary Impact (Model Estimated Outputs).</p

Model calculated survival curves overlaid with observed clinical trial data [19].

<p>The survival curves derived from the estimated model were similar to those found in previous reported clinical trial data [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134587#pone.0134587.ref019" target="_blank">19</a>]</p

One-way sensitivity analyses based on the third-year budgetary impact.

<p>The estimated model was most sensitive to changes in the cost of ATO in the consolidation phase, in parameters determining the number of patients with APL, and in the cost of in-patient treatment and monitoring of AIDA patients during consolidation.</p

Cumulative Patient Counts by Health State at Year End (Model Estimated Outputs).

<p>^†The total number of patients may not add up to 82 per year due to rounding.</p><p>Cumulative Patient Counts by Health State at Year End (Model Estimated Outputs).</p

Clinical Transition Probabilities.

<p>Clinical Transition Probabilities.</p

Markov model of first-line chemotherapy with three disease states.

<p>Markov model of first-line chemotherapy with three disease states.</p

Additional file 1: Figures S1A, S1B, and S1C. of PML-RAR alpha induces the downmodulation of HHEX: a key event responsible for the induction of an angiogenetic response

Figure S1A Analysis of HHEX (top panel) and VEGF-A (middle panel) reported in 176 primary AMLs on the TCGA platform. The HHEX/VEGF-A ratio is reported in the bottom panel. Figure S1B Correlation between HHEX and VEGF-A levels observed in 18 primary APLs in the present study (p = 0.0484) and in 16 primary APLs in the TCGA data (p = 0.0284). Figure S1C Correlation between HHEX and VEGF-A levels observed in 18 primary APLs (p = 00484) and in 20 primary M5 AMLs in the TCGA data (p = 0.0174). (ZIP 689 kb

A: <i>In vitro</i> immunomodulatory effect of HD-MSCs and ALL-MSCs on HD-PBMCs.

<p>The graph shows the proliferation of healthy donor peripheral blood mononuclear cells (HD-PBMCs) stimulated with phytohemagglutinin (PHA) either in the presence or in the absence of HD-MSCs or ALL-MSCs, generated at disease onset and subsequent time-points of treatment (day+15; day+33; day+78). Each bar represents the percentage of proliferation of 10⁵ PBMCs, in the presence of two different MSC∶PBMC ratios (MSC∶PBMC ratio of 1∶2 and 1∶10), calculated by measuring ³H-thymidine incorporation after 3-day co-culture. The counts per minute (cpm) values at each cell concentration were normalized to the cpm of PBMCs without MSCs in each experiment. Each bar represents the mean ± SD of multiple experiments (each point being in triplicate) with MSCs obtained from 10 ALL patients (at each time-point) and 10 HDs. <b>B: </b><b>Quantification of cytokines and growth factors in supernatants of co-cultures of HD-MSCs and ALL-MSCs (isolated at day+0) with PBMCs, after 72-hour incubation with PHA.</b> An increase in anti-inflammatory cytokines (<i>i.e.</i> IL6, IL10 and TGFb) was detected in the presence of both HD-MSCs and ALL-MSCs, as compared with PHA-stimulated PBMC cultures. A decrease in pro-inflammatory cytokines and growth factors (GM-CSF, IL2 and IFNg) was revealed in supernatants collected from the same co-cultures. Each bar represents the mean +/−SD of the results from experiments performed with the same HD- and ALL-MSC samples employed in the PBMC proliferation assays. Results are expressed as pg/ml.</p

Proliferative capacity of ALL-MSCs as compared with HD-MSCs.

<p>Calculated cumulative population doublings (PDs) from P1 to P5 of MSCs isolated from HDs and from ALL patients at diagnosis and at following time-points of treatment, namely day+15, +33 and +78. The data represent the mean of 10 HD-MSCs and 10 ALL-MSCs. P values less than 0.05 were considered to be statistically significant.</p

Mean percentage of proliferation of healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with PHA in the presence of HD-MSCs, as compared with ALL-MSCs generated at day+0; +15; +33; +78 at two different MSC∶PBMC ratios (1∶2; 1∶10).

<p>Each value represents the mean ± SD of multiple experiments (each point being in triplicate). PBMC proliferation stimulated with PHA in the absence of MSCs was 71.80%. P values less than 0.05 were considered to be statistically significant.</p