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Revised International Prognostic Scoring System for Myelodysplastic Syndromes

Peter L. Greenberg, Heinz Tuechler, Julie Schanz, Guillermo Sanz, Guillermo Garcia-Manero, Francesc Solé, John M. Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Alessandro Levis, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Christa Fonatsch, Michelle M. Le Beau, Marilyn L. Slovak, Otto Krieger, Michael Luebbert, Jaroslaw Maciejewski, Silvia M. M. Magalhaes, Yasushi Miyazaki, Michael Pfeilstöcker, Mikkael Sekeres, Wolfgang R. Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A. van de Loosdrecht, Ulrich Germing and Detlef Haase

Data supplements

Article Figures & Data

Figures

  • Figure 1

    IWG-PM patients marrow blast subgroups. Impact on survival. Survival related to MDS patients' individual marrow blast percent categories (Kaplan-Meier curves, Dxy 0.3, P < .001). The number of patients in each category and their proportional representation are shown in Table 1.

  • Figure 2

    IWG-PM patients marrow blast subgroups: Impact on AML evolution. Progression to AML related to MDS patients' individual marrow blast percent categories (Kaplan-Meier curves, Dxy 0.47, P < .001). The number of patients in each category and their proportional representation are shown in Table 1.

  • Figure 3

    Survival based on IPSS-R prognostic risk-based categories. Survival related to MDS patients' prognostic risk categories (Kaplan-Meier curves, n = 7012; Dxy 0.43, P < .001). The number of patients in each category and their proportional representation are shown in Table 1.

  • Figure 4

    AML evolution based on IPSS-R prognostic risk-based categories. Progression to AML related to MDS patients' prognostic risk categories (Kaplan-Meier curves, n = 6485; Dxy 0.52, P < .001). The number of patients in each category and their proportional representation are shown in Table 1.

  • Figure 5

    Survival based on patient ages > 60 years vs ≤ 60 years related to their IPSS-R 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.

  • Figure 6

    Age-adjusted IPSS-R risk categories. The nomogram describes predicted survival based on patient age and IPSS-R risk status (IPSS-RA). To determine an age-adjusted risk categorization, for example, follow the horizontal line, starting at the IPSS-R risk score 3.5 on the vertical axis (Int [Intermediate] risk category per Table 4) to the age of the patient and record the color at that point. If the patient is 45 years, the 3.5′-line and the vertical 45-year line cross in the gray field, placing the patient in the Low risk category, whereas if the patient is 95 years the 3.5′-line and the 95-year line cross in the yellow field, placing the patient in the Intermediate risk category. As indicated, for most patients in the Very high risk category there is no change of risk group, whereas for most patients in the lower risk categories there is greater possibility of category change. Note the “dotted” vertical line at 70 years, which is at the median age of the IWG-PM patient cohort from which the basic risk category scores were calculated (ie, without need for age correction for these patients). The formula to generate the age-adjusted risk score in the figure: (years − 70) × [0.05 − (IPSS-R risk score × 0.005)]. Example: For the 45-year-old patient with an IPSS-R risk score of 3.5 (Intermediate risk): (45-70) × [0.05 − (3.5 × 0.005)] = −0.81. Thus, 3.5-0.8 = 2.7 [age-adjusted IPSS-R score, IPSS-RA: Low risk].

  • Figure 7

    Comparison of IPSS-R and IPSS subgroups within the IWG-PM database patient cohort. Vertical axis represents IPSS-R categories' and horizontal axis, IPSS categories. The proportion of patients in each category is shown in Table 9. Kendall τ = 0.73.

Tables

  • Table 1

    Clinical variables of MDS patients

    No. of patients% of patientsSurvival years, medianDxy (95% CI; P*)No. of patients% of patientsAML/25% yDxy (95% CI; P*)
    Cytogenetics7012100.256485100.27
        Very good25545.4(.23-.26)2553NR(.24-.31)
        Good5069724.84657729.4
        Intermediate947132.7875142.5
        Poor28341.527641.7
        Very poor45870.745270.7
    BM blasts7012100.306485100.47
        0-2%3279475.9(.28-.32)300446NR(.44-.50)
        > 2- < 5%1266184.21172188.5
        5-10%1377192.31263202.2
        > 10%-30%1090161.31046161.0
        > 10%-20%(901)(13)(1.3)(860)(13)(0.93)
        > 20%-30%(189)(3)(1.4)(186)(3)(1.0)
    Hemoglobin, g/dL7012100.216485100.16
        ≥ 103377485.5(.19-.23)3109489.5(.12-.19)
        8-< 102464352.92286355.5
        < 81171172.01090172.4
    Platelets7012100.236485100.17
        ≥ 1004195605.1(.21-.25)3823598.7(.14-.21)
        50- < 1001469212.81368213.1
        < 501348191.61294203.1
    ANC7012100.116485100.16
        ≥ 0.85758824.4(.10-.13)5303829.2(.13-.19)
        < 0.81254181.91182181.9
    IPSS-R7012100.436485100.52
        Very low1313198.8(.42-.45)121219NR(.49-.55)
        Low2646385.323953710.8
        Intermediate1433203.01310203.2
        High898131.6857131.4
        Very high722100.8711110.7
    Sex7012100.076485100.04
        Male4243613.3(.05-.09)3962615.8(.00-.07)
        Female2769394.82523398.0(.030)
    Age7012100.056485−.02
        ≤ 60 y1582235.7(.03-.06)1489238.1(−.05-.01)
        > 60 y5430773.54996776.1(.082)
    ECOG Performance Status249636.16248938.09
        0751304.3(.13-.18)748308.8(.04-.15)
        11477592.21473596.3(.005)
        2-4268111.6268113.5
    Serum ferritin304943.16274742.11
        ≤ 350 ng/mL1602536.3(.13-.20)143552NR(.05-.17)
        > 350 ng/mL1447474.213124814.5(.004)
    Serum LDH425761.12413064.12
        Normal3103734.1(.10-.14)3007739.2(.08-.16)
        High1154272.11123273.2
    Serum β2-microglobulin100514.14 (.10-.18)100515.02 (−.08-.11)
        ≤ 2 g/mL263263.8263266.7(.498)
        > 2 g/mL742741.7742744.6
    Marrow fibrosis132319.04118318.05
        No1158885.2(.01-.07)10558914.5(−.01-.12)
        Yes165123.2(.004)128114.8(.069)
    RBC transfusion dependence293342.26264541.27
        No2003686.9(.23-.29)18086814.5(.22-.32)
        Yes930322.3837322.1
    IPSS7008100.376481100.48
        Low2625377.0(.35-.39)239437NR(.45-.51)
        Intermediate-12778403.62541396.1
        Intermediate-21126161.51074171.2
        High47970.947270.7
    • AML/25% indicates time for 25% of patients to develop AML.

    • * All univariate P values not explicitly stated are P < .001.

    • × 109/L.

  • Table 2

    MDS Cytogenetic Scoring System

    Prognostic subgroups, % of patientsCytogenetic abnormalitiesMedian survival,* yMedian AML evolution, 25%,* yHazard ratios OS/AML*Hazard ratios OS/AML
    Very good (4%*/3%)−Y, del(11q)5.4NR0.7/0.40.5/0.5
    Good (72%*/66%)Normal, del(5q), del(12p), del(20q), double including del(5q)4.89.41/11/1
    Intermediate (13%*/19%)del(7q), +8, +19, i(17q), any other single or double independent clones2.72.51.5/1.81.6/2.2
    Poor (4%*/5%)−7, inv(3)/t(3q)/del(3q), double including −7/del(7q), complex: 3 abnormalities1.51.72.3/2.32.6/3.4
    Very poor (7%*/7%)Complex: > 3 abnormalities0.70.73.8/3.64.2/4.9
    • OS indicates overall survival; and NR, not reached.

    • * Data from patients in this IWG-PM database, multivariate analysis (n = 7012).

    • Data from Schanz et al8 (n = 2754).

  • Table 3

    IPSS-R prognostic score values

    Prognostic variable00.511.5234
    CytogeneticsVery goodGoodIntermediatePoorVery poor
    BM blast, %≤ 2> 2%- < 5%5%-10%> 10%
    Hemoglobin≥ 108- < 10< 8
    Platelets≥ 10050-< 100< 50
    ANC≥ 0.8< 0.8
    • — indicates not applicable.

  • Table 4

    IPSS-R prognostic risk categories/scores

    Risk categoryRisk score
    Very low≤ 1.5
    Low> 1.5-3
    Intermediate> 3-4.5
    High> 4.5-6
    Very high> 6
  • Table 5

    IPSS-R prognostic risk category clinical outcomes

    No. of patientsVery lowLowIntermediateHighVery high
    Patients, %70121938201310
    Survival, all*8.85.33.01.60.8
    (7.8-9.9)(5.1-5.7)(2.7-3.3)(1.5-1.7)(0.7-0.8)
    Hazard ratio0.51.02.03.28.0
    (95% CI)(0.46-0.59)(0.93-1.1)(1.8-2.1)(2.9-3.5)(7.2-8.8)
    Patients, %64851937201311
    AML/25%*NR10.83.21.40.73
    (14.5-NR)(9.2-NR)(2.8-4.4)(1.1-1.7)(0.7-0.9)
    Hazard ratio0.51.03.06.212.7
    (95% CI)(0.4-0.6)(0.9-1.2)(2.7-3.5)(5.4-7.2)(10.6-15.2)
    • NR indicates not reached.

    • * Medians, years (95% CI), P < .001.

    • Median time to 25% AML evolution (95% CIs), P < .001.

  • Table 6

    IPSS-R survival related to age

    Ages, yIPSS-R prognostic risk categories
    Very lowLowIntermediateHighVery high
    All8.85.33.01.60.8
    ≤ 60NR8.85.22.10.9
    (13.0-NR)(8.1-12.1)(4.0-7.7)(1.7-2.8)(0.8-1.0)
    > 60-7010.26.13.31.60.8
    (9.1-NR)(5.3-7.4)(2.5-4.0)(1.5-2.0)(0.7-1.0)
    > 70-807.04.72.71.50.7
    (5.9-9.0)(4.3-5.3)(2.4-3.1)(1.3-1.7)(0.6-0.8)
    > 805.23.21.81.50.7
    (4.2-5.9)(2.8-3.8)(1.6-2.6)(1.2-1.7)(0.5-0.8)
    ≤ 60 (median, 52)NR8.85.22.10.9
    > 60 (median, 74)7.54.72.61.50.7
    ≤ 70 (median, 62)13.37.73.91.70.9
    > 70 (median, 77)5.94.22.51.40.7
    • Data are median (95% CI).

    • NR indicates not reached.

  • Table 7

    Mortality of MDS patients with or without AML evolution

    Risk categoryNo. (%) of patientsPatients who
    Died, no. (%)Died with AML, no. (%)Died without AML, no. (%)
    Very low1313350 (27)46 (13)304 (87)
    Low26461053 (40)174 (17)861 (83)
    Intermediate1433782 (55)205 (26)568 (74)
    High898633 (71)207 (33)421 (67)
    Very high722619 (86)193 (31)422 (69)
    Total70123437 (49)825 (24)2576 (76)
  • Table 8

    Refinements of the IPSS-R beyond the IPSS

    1. New marrow blast categories
        ≤ 2%, > 2%-< 5%, 5%-10%, > 10%-30%
    2. Refined cytogenetic abnormalities and risk groups
        16 (vs 6) specific abnormalities, 5 (vs 3) subgroups
    3. Evaluation of depth of cytopenias
        Clinically and statistically relevant cutpoints used
    4. Inclusion of differentiating features*
        Age, Performance Status, serum ferritin, LDH; β2-microglobulin
    5. Prognostic model with 5 (vs 4) risk categories
        Improved predictive power
    • * For survival.

    • Provisional.

  • Table 9

    Distribution (%) of IWG-PM patients who would previously have been categorized by IPSS now categorized by IPSS-R

    IPSSVery lowLowIntermediateHighVery High
    Low (37)4452400
    Intermediate-1 (40)64538101
    Intermediate-2 (16)01244530
    High (7)0031978
    Total1938201310
    • % indicated within rows. Kendall tau = 0.73.

  • Table 10

    IPSS-R prognostic risk category: clinical outcomes of Medical University of Vienna patients (n = 200)

    Very lowLowIntermediateHighVery high
    Patients, %213818148
    Survival
        All*9.36.33.41.20.6
        Hazard ratio0.812.14.39.4
        95% CI0.4-1.50.7-1.51.3-3.52.4-7.74.3-20.8
    AML transformation
        AML/25%*NRNR2.40.80.6
        Hazard ratio018.018.752.2
        95% CI0-∞0.3-3.93.1-20.57.0-49.713.8-198.2
    • NR indicates not reached.

    • * Medians, years (95% CI; P < .001).

    • Median time to 25% AML evolution (95% CI; P < .001).