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T. de Witte et al.
evaluated with the aim of estimating the prognostic impact of regular RBCT and to validate RBCT-free survival as an early clinical endpoint in this patient population. The refer- ence endpoint was progression-free survival (PFS), because both progression and death indicate the end of a relatively stable phase of LR-MDS.
A cohort of 1,267 patients with all relevant data available was included in this analysis. The patients were subdivided for the landmark analysis into four groups: no transfusions, >0 to <0.75 units/month (low transfusion dose), 0.75-1.75 units/month (mid transfusion dose) and >1.75 units/month (high transfusion dose). The greatest effect, compared to the non-transfused patients, occurred in patients receiving transfusions at low dose densities, since the impaired out- come of the mid and high transfusion density group was similar (Figure 2). In multivariable analysis, RBCT dose den- sity retained statistical significance at P<10-4.
Since treatment with ESA, lenalidomide and iron chela- tors may improve erythropoiesis and reduce the need for RBCT, these variables were included in the regression
model. This analysis resulted in an effect for the dose den- sity similar to the previous analyses at P<10-4.21 However, the dose density effect continues to increase beyond one unit per month after correction for the three interventions (ESA, iron chelation and lenalidomide) up until a dose of six units per month (Figure 3). The relative log ratios on PFS of this analysis clearly showed that the deleterious effect of transfusions already occurred at a very low transfusion bur- den (<3 units per 16 weeks as defined in the revised International Working Group, IWG) report, confirming the outcome of the landmark analysis (see above). It is impor- tant to realize that patients with a transfusion dose of 1-2 units per 16 weeks are considered to be untransfused in the recently revised IWG report, but are recommended to be studied in future clinical trials.21
Relevance of patient-reported outcomes in lower-risk myelodysplastic syndromes
Health related quality of life is an important patient- reported outcome (PRO). It provides specific information on
Figure 1. Kaplan-Meier plots of overall survival from land- mark according to the 6-month European LeukemiaNet MDS (EUMDS) classifier based on platelet drop >25% and red blood cell transfusion (RBCT)-dependency at landmark. Black: no criteria (no platelet drop >25% or RBCT-dependen- cy at landmark); red: either one of the two criteria; green: both criteria.
Figure 2. Kaplan-Meier plots of progression- free survival (PFS) according to transfusion status at the landmark of visit 3 (1 year after registration). Kaplan -Meier plot of PFS of patients receiving no transfusions (red line) or transfusions at a low dose density: from >0 to <0.75 units per month (green line); mid dose density: 0.75-1.75 units per month (purple line); high dose density >1.75 units per month (blue line).
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haematologica | 2020; 105(11)