Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.

RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.

Determination of time-dependent partition coefficients for several pesticides using diffusion theory.

Diffusion-retarded partitioning of pesticides with aggregated soils results in a time-dependent partition coefficient (Kd') which is different at equilibrium from the partition coefficient derived from conventional 24-h batch studies (Kd) measured on dispersed soil. An experiment was undertaken to determine the importance of Kd' for the prediction of pesticide concentrations in solutions bathing artificial soil aggregates and to determine whether diffusion theory could accurately predict the concentrations. Two clay soils were mixed with polyacrylamide to create artificial aggregates of 0.8, 1.4 and 1.7 cm diameter when dry. After saturation, the aggregates were immersed in solutions containing isoproturon or a mixture of isoproturon, chlorotoluron and triasulfuron. The decline with time of the pesticide concentrations in the bathing solution was monitored and the results were compared with predictions from a diffusion-based model. The effective diffusion coefficients of the compounds were obtained by either fitting the non-linear diffusion model to the data (D(ef)) or by independent calculations based on the properties of the compounds and of the aggregates (D(ec)). The diffusion model was able to predict the temporal variation in pesticide concentrations in the bathing solution reasonably well whether D(ef) or D(ec) values were used. However, equilibrium concentrations in solution were sometimes overestimated due to increased sorption with time at the particle scale. Overall, the ratio between D(ef) and D(ec) ranged from 0.23 to 0.95 which was a reasonable variation when compared to the range of aggregate sizes used in the experiments and of the Kd values of the compounds.