Validation of WHO Classification-Based Prognostic Scoring System (WPSS) for Myelodysplastic

Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM)

By Matteo G. Della Porta,et al.

Supplemental material

Supplemental Table 1. Comparison of severe anemia defined by using specific hemoglobin thresholds vs. RBC transfusion dependency (Kendall’s Tau 0.52, P<.001).

RBC transfusion-dependency
Hemoglobin thresholds / No / Yes / Total
High / 1531 (81%) / 356 (19%) / 1887
Low / 158 (25%) / 471 (75%) / 629
Total / 1689 / 827 / 2516

Supplemental Table 2. Distribution (%) of MDS patients categorized by WPSS adopting transfusion-dependency vs. WPSS adopting specific Hb thresholds (Kendall’s Tau 0.91, P<.001).

WPSS score adopting transfusion-dependency
WPSS score adopting Hb thresholds / Very low / Low / Intermediate / High / Very high / Total
Very low / 481 (84,7) / 87 (15,3) / 0 / 0 / 0 / 568
Low / 34 (4,5) / 622 (81.8) / 32 (13.7) / 0 / 0 / 741
Intermediate / 0 / 32 (7.2) / 355 (79.4) / 60 (13.4) / 0 / 447
High / 0 / 0 / 17 (3.8) / 409 (91.5) / 21 (4.7) / 447
Very high / 0 / 0 / 0 / 11 (11.1) / 88 (88.9) / 99
Total / 515 / 741 / 476 / 480 / 109 / 2321

Supplemental Table 3. Distribution (%) of the IPSS-R based cytogenetic risk groups among different WHO categories.

IPSS-R based cytogenetics
WHO 2008 categories / Very good / Good / Intermediate / Poor / Very poor / Total
RCUD / 35 (4%) / 728 (78%) / 117 (13%) / 26 (3%) / 22 (2%) / 928
RARS / 36 (6%) / 523 (80%) / 72 (11%) / 11 (2%) / 13 (2%) / 655
MDSdel5q / 0 / 209 (94%) / 3 (1%) / 4 (2%) / 7 (3%) / 223
RCMD / 66 (4%) / 1210 (77%) / 207 (13%) / 47 (3%) / 46 (3%) / 1576
RAEB1 / 27 (3%) / 580 (63%) / 138 (15%) / 61 (7%) / 122 (13%) / 928
RAEB2 / 13 (1%) / 604 (59%) / 157 (16%) / 74 (7%) / 168 (17%) / 1016
Total / 177 (3%) / 3854 (72%) / 649 (13%) / 223 (4%) / 378 (7%) / 5326

Abbreviations: refractory cytopenia with unilineage dysplasia (RCUD), refractory anemia with ring sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD, MDS with isolated deletion of 5q (MDSdel5q), refractory anemia with excess blasts (RAEB) type 1 and 2.

Supplemental Table 4. Integration of new cytogenetic features according to IPSS-R criteria into WPSS. In a first Cox multivariable model, single WPSS variables were included as covariates together with IPSSR-based cytogenetics. Score points for all categories of each prognostic feature are reported below. # Dxy for overall survival was 0.40, while Dxy for AML progression was 0.52

Variable / 0 / 1.2 / 1.6 / 2.4 / 3.6 / 4.8
WHO category / RCUD, RARS, MDSdel5q / RCMD / RAEB1 / RAEB2
Hb thresholds / High level / Low level
Cytogenetics
(IPSS-R criteria) / Very good / Good / Intermediate / Poor / Very poor

# Score - limits for risk categories: (lower bound - upper bound):

very low >=0 <=1.6

low >1.6 <=3

intermediate>3 <=4.4

high >4.4 <=5.6

very high >5.6 <=10

As a second step, a further analysis was carried out considering a weight of 1 for all categories of each prognostic feature as reported below. ## Dxy for overall survival was 0.43, while Dxy for AML progression was 0.53

Variable / 0 / 1 / 2 / 3 / 4
WHO category / RCUD, RARS, MDSdel5q / RCMD / RAEB1 / RAEB2
Hb thresholds / High level / Low level
Cytogenetics
(IPSS-R criteria) / Very good / Good / Intermediate / Poor / Very Poor

## Score - final categories:

very low = 0-1

low = 2

intermediate = 3

high = 4-5

very high > 5

Supplemental Table 5. Distribution (%) of MDS patients categorized into WPSS categories by WPSS-R including new cytogenetic features (Kendall’s Tau 0.96, P<.001).

WPSS score including new cytogenetic features
WPSS score / Very low / Low / Intermediate / High / Very high / Total
Very low / 1127 (99.9) / 1 (0,1) / 0 / 0 / 0 / 1128
Low / 85 (5.8) / 1390 (94.2) / 1 (0.1) / 0 / 0 / 1476
Intermediate / 12 (1.2) / 77 (7.7) / 887 (88.2) / 30 (3) / 0 / 1006
High / 0 / 11 (0.8) / 52 (4) / 1158 (88.8) / 83 (6.4) / 1304
Very high / 0 / 0 / 0 / 26 (6.3) / 386 (93.7) / 412
Total / 1124 / 1479 / 940 / 1214 / 469 / 5326

Supplemental Table 6. WPSS survival (months) related to age

WPSS prognostic risk categories
Very low / Low / Intermediate / High / Very high

All patients

/ 98 / 76 / 44 / 21 / 9

Ages

<=55 / 207 / NR / 92 / 34 / 11
>55 to <=65 / 121 / 96 / 66 / 23 / 8
>65 to <=70 / 105 / 80 / 44 / 19 / 10
>70 to <=75 / 84 / 73 / 35 / 22 / 9
>75 / 61 / 51 / 32 / 18 / 8

Supplemental Table 7. Differentiating variables for survival: score values*

Parameter

/ Variables / Prognostic power (gain in Dxy) / Raw score Points

ECOG performance status

/ 0 vs. 1 vs. 2.4 / 0.01 / -0.6/0.1/0.9
Serum ferritin / <=170 vs. >170 to <= 350 vs. >350 to <=700 vs. > 700 ng/ml / 0.03 / -0.6/-0.2/0.2/0.6
Serum LDH / Normal vs. High / 0.01 / -0.2/0.4
Serum B2microglobulin / <= vs. > 2 g/ml / 0.05 / -0.6/-0.2/0.3/0.8
Marrow fibrosis / No vs. Yes / NANS / -

*Based on both multivariate p ≤0.001 and gain in Dxy concordance coefficient/predictive

value (Cox proportional hazard models).

NANS = Not applicable as gain in Dxy is not statistically significant

**To include the impact of one of the above listed features on survival risk, the

appropriate raw score point/decimal should be added to the WPSS score (before

categorization) and the resulting score should be categorized. The inclusion of more than one feature at a time in this table is not permitted as more complicated weighing systems would then be required.

Examples:

Patient 1:

- WPSS score without inclusion of a differentiating feature: 1 ("Low")

- serum ferritin >700 ng/ml (raw score point=0.6)

- resulting WPSS score: 1.6; Thus, adjusted WPSS risk category: "Intermediate"

Patient 2:

- WPSS score without inclusion of a differentiating feature: 2 ("Intermediate”)

- ECOG performance status grade 2 (raw score point=0.9)

- resulting WPSS score: 2.9; Thus, adjusted risk category: "High"

Supplemental Figure 1. Survival based on patient ages > 60 years vs < 60 years related to their WPSS prognostic risk-based categories (Kaplan-Meier curves). Age-related differential survivals are shown for patients in all groups, particularly for those in lower risk categories.

Time (months)Time (months)

Supplemental Figure 2. Outcome of the WPSS population stratified according to additional clinical features, including performance status, serum ferritin, LDH, b2-microglobulin and marrow fibrosis

A) ECOG performance status