5  The MDS Natural History Study

Key Tables from the MDS Natural History Study

Author

Ashwin Kishtagari

Published

August 19, 2026

Show code 
library(gt)
library(dplyr)
library(tibble)

5.1 Overview

  • This document presents the key tables from “A novel approach to defining progression in MDS and precursor myeloid conditions in The MDS Natural History Study” (DeZern et al., ADV-2025-018770R1, NCT02775383).

  • The MDS NHS enrolled 1,177 individuals with MDS or precursor conditions from 102 US centers.

5.2 Table 1: Definitions of Progression Metrics

Show code 
tibble::tribble(
  ~Category, ~Event, ~Specification, ~N,
  "Worsening Disease", "Follow-up local site re-diagnosis",
  "Baseline at-risk with subsequent re-diagnosis of MDS or AML<30%, or progression to AML\u226530%, >30d after enrollment", 87L,
  "Worsening Disease", "Change in BM blasts",
  "Increase in BM blasts \u226550% from baseline to \u22655%", 81L,
  "Worsening Disease", "Change in ANC",
  "Drop in ANC \u226550% from max/baseline to <1,000 cells/\u00b5L, not on therapy", 132L,
  "Worsening Disease", "Change in platelets",
  "Drop in platelet count \u226550% from max/baseline to <100,000/\u00b5L, not on therapy", 204L,
  "Worsening Disease", "Change in hemoglobin",
  "Drop in Hg \u22651.5 g/dL from max/baseline to <10 g/dL, not on therapy/transfusions", 12L,
  "Disease-Directed Therapy", "End therapy: progression",
  "Documented reason for ending therapy indicates progression, >30d after enrollment", 35L,
  "Disease-Directed Therapy", "End therapy: worsening cytopenia",
  "Documented reason indicates worsening cytopenia/decline, >30d post enrollment", 3L,
  "Disease-Directed Therapy", "Initiation of disease-directed therapy",
  "Initiation of disease-directed therapy \u226590d after enrollment", 132L,
  "Disease-Directed Therapy", "Re-initiation of therapy",
  "Initiation of therapy in patients not on therapy \u226590d", 30L,
  "Disease-Directed Therapy", "Stem cell transplant",
  "Receipt of stem cell transplant therapy", 43L,
  "Transfusion Dependency", "RBC transfusion: to low dependency",
  "Non/minimally dependent to low dependent (5\u201311 units/6 mo), not on active therapy", 62L,
  "Transfusion Dependency", "RBC transfusion: to high dependency",
  "Non/minimally dependent to high dependent (\u226512 units/6 mo), not on active therapy", 19L,
  "Disease-Related Death", "MDS/AML-related death",
  "Primary cause of death: MDS, AML, CMML, or Leukemia", 113L
) |>
  gt(groupname_col = "Category") |>
  cols_label(
    Event = md("**Progression Event**"),
    Specification = md("**Specifications**"),
    N = md("**N**")
  ) |>
  tab_header(
    title = md("**Table 1. Definitions of Progression Metrics**"),
    subtitle = md("*Refined clinical and pathologic criteria for the MDS NHS*")
  ) |>
  tab_footnote(
    footnote = "Data freeze August 1, 2025. Total unique individuals with \u22651 event: N = 468.",
    locations = cells_column_labels(columns = N)
  ) |>
  tab_style(
    style = list(cell_fill(color = "#f0f7ff"), cell_text(weight = "bold")),
    locations = cells_row_groups()
  ) |>
  cols_width(Event ~ px(260), Specification ~ px(420), N ~ px(55)) |>
  tab_options(
    table.font.size = px(13),
    heading.title.font.size = px(17),
    heading.subtitle.font.size = px(13),
    table.border.top.color = "#1a5276",
    table.border.top.width = px(3),
    heading.border.bottom.color = "#1a5276",
    column_labels.border.bottom.color = "#1a5276",
    column_labels.border.bottom.width = px(2),
    row_group.border.top.color = "#7fb3d8",
    table_body.hlines.color = "#e8e8e8"
  ) |>
  opt_row_striping()
Table 5.1: Definitions of metrics of progression used in the MDS NHS analysis
Table 1. Definitions of Progression Metrics
Refined clinical and pathologic criteria for the MDS NHS
Progression Event Specifications N1
Worsening Disease
Follow-up local site re-diagnosis Baseline at-risk with subsequent re-diagnosis of MDS or AML<30%, or progression to AML≥30%, >30d after enrollment 87
Change in BM blasts Increase in BM blasts ≥50% from baseline to ≥5% 81
Change in ANC Drop in ANC ≥50% from max/baseline to <1,000 cells/µL, not on therapy 132
Change in platelets Drop in platelet count ≥50% from max/baseline to <100,000/µL, not on therapy 204
Change in hemoglobin Drop in Hg ≥1.5 g/dL from max/baseline to <10 g/dL, not on therapy/transfusions 12
Disease-Directed Therapy
End therapy: progression Documented reason for ending therapy indicates progression, >30d after enrollment 35
End therapy: worsening cytopenia Documented reason indicates worsening cytopenia/decline, >30d post enrollment 3
Initiation of disease-directed therapy Initiation of disease-directed therapy ≥90d after enrollment 132
Re-initiation of therapy Initiation of therapy in patients not on therapy ≥90d 30
Stem cell transplant Receipt of stem cell transplant therapy 43
Transfusion Dependency
RBC transfusion: to low dependency Non/minimally dependent to low dependent (5–11 units/6 mo), not on active therapy 62
RBC transfusion: to high dependency Non/minimally dependent to high dependent (≥12 units/6 mo), not on active therapy 19
Disease-Related Death
MDS/AML-related death Primary cause of death: MDS, AML, CMML, or Leukemia 113
1 Data freeze August 1, 2025. Total unique individuals with ≥1 event: N = 468.

5.3 Table 2: Patient Population Characteristics

Show code 
char_data <- tibble::tribble(
  ~Characteristic, ~AllMDS, ~ICUS_IDUS, ~CCUS, ~P1,
  ~LR_MDS, ~HR_MDS, ~UNK_MDS, ~P2,

  "Female", "178 (30%)", "123 (50%)", "82 (29%)", "0.018",
  "94 (30%)", "56 (38%)", "28 (23%)", "",
  "Male", "407 (70%)", "124 (50%)", "197 (71%)", "",
  "221 (70%)", "93 (62%)", "93 (77%)", "",

  "<60 years", "44 (8%)", "63 (26%)", "19 (7%)", "<0.001",
  "24 (8%)", "17 (11%)", "3 (2%)", "0.090",
  "60\u201369 years", "116 (20%)", "66 (27%)", "54 (19%)", "",
  "63 (20%)", "33 (22%)", "20 (17%)", "",
  "70\u201379 years", "274 (47%)", "80 (32%)", "119 (43%)", "",
  "142 (45%)", "69 (46%)", "63 (52%)", "",
  "80\u201389 years", "131 (22%)", "37 (15%)", "80 (29%)", "",
  "75 (24%)", "26 (17%)", "30 (25%)", "",
  "\u226590 years", "20 (3%)", "1 (0%)", "7 (3%)", "",
  "11 (3%)", "4 (3%)", "5 (4%)", "",

  "White", "539 (92%)", "211 (85%)", "256 (92%)", "0.020",
  "293 (93%)", "135 (91%)", "111 (92%)", "0.648",
  "Black or African American", "26 (4%)", "16 (6%)", "6 (2%)", "",
  "12 (4%)", "7 (5%)", "7 (6%)", "",
  "Asian", "4 (1%)", "7 (3%)", "5 (2%)", "",
  "1 (0%)", "1 (1%)", "2 (2%)", "",

  "Hispanic or Latino", "22 (4%)", "18 (7%)", "9 (3%)", "0.027",
  "13 (4%)", "3 (2%)", "6 (5%)", "0.366",
  "Not Hispanic or Latino", "544 (93%)", "218 (88%)", "256 (92%)", "",
  "290 (92%)", "141 (95%)", "113 (93%)", "",

  "Never smoked", "250 (43%)", "139 (56%)", "122 (44%)", "<0.001",
  "145 (46%)", "52 (35%)", "53 (44%)", "0.118",
  "Smoker", "334 (57%)", "108 (44%)", "157 (56%)", "",
  "170 (54%)", "96 (65%)", "68 (56%)", "",

  "No prior cancers", "412 (70%)", "195 (79%)", "199 (71%)", "0.082",
  "225 (71%)", "101 (68%)", "86 (71%)", "0.830",
  "Prior cancers (\u22651)", "173 (30%)", "52 (21%)", "80 (29%)", "",
  "90 (29%)", "48 (32%)", "35 (29%)", ""
) |>
  mutate(Section = case_when(
    Characteristic %in% c("Female", "Male") ~ "Sex \u2014 no. (%)",
    Characteristic %in% c("<60 years", "60\u201369 years", "70\u201379 years",
                          "80\u201389 years", "\u226590 years") ~ "Age Group \u2014 no. (%)",
    Characteristic %in% c("White", "Black or African American",
                          "Asian") ~ "Race \u2014 no. (%)",
    Characteristic %in% c("Hispanic or Latino",
                          "Not Hispanic or Latino") ~ "Ethnicity \u2014 no. (%)",
    Characteristic %in% c("Never smoked", "Smoker") ~ "Smoking History \u2014 no. (%)",
    TRUE ~ "Prior Cancer \u2014 no. (%)"
  ))

char_data |>
  gt(groupname_col = "Section") |>
  cols_label(
    Characteristic = "",
    AllMDS = md("**All MDS**<br>(N=613)"),
    ICUS_IDUS = md("**ICUS/IDUS**<br>(N=264)"),
    CCUS = md("**CCUS**<br>(N=300)"),
    P1 = md("***P***"),
    LR_MDS = md("**LR-MDS**<br>(N=330)"),
    HR_MDS = md("**HR-MDS**<br>(N=159)"),
    UNK_MDS = md("**UNK-MDS**<br>(N=124)"),
    P2 = md("***P***")
  ) |>
  tab_header(
    title = md("**Table 2. Characteristics of the National MDS Study Population**"),
    subtitle = md("*Comparison across diagnostic categories*")
  ) |>
  tab_spanner(
    label = md("**By Overall Diagnosis**"),
    columns = c(AllMDS, ICUS_IDUS, CCUS, P1)
  ) |>
  tab_spanner(
    label = md("**MDS by IPSS-R Risk**"),
    columns = c(LR_MDS, HR_MDS, UNK_MDS, P2)
  ) |>
  tab_style(
    style = cell_text(weight = "bold", color = "#1a5276"),
    locations = cells_body(columns = c(P1, P2))
  ) |>
  tab_style(
    style = list(cell_fill(color = "#eaf2fa"), cell_text(weight = "bold")),
    locations = cells_row_groups()
  ) |>
  tab_footnote(
    footnote = md("P-values from Fisher\u2019s Exact tests (proportions) and Kruskal-Wallis tests (continuous).")
  ) |>
  tab_footnote(
    footnote = md("LR-MDS: IPSS-R \u2264 3.5; HR-MDS: IPSS-R > 3.5; UNK-MDS: IPSS-R not calculated.")
  ) |>
  tab_options(
    table.font.size = px(12),
    heading.title.font.size = px(17),
    heading.subtitle.font.size = px(13),
    table.border.top.color = "#1a5276",
    table.border.top.width = px(3),
    heading.border.bottom.color = "#1a5276",
    column_labels.border.bottom.color = "#1a5276",
    column_labels.border.bottom.width = px(2),
    row_group.border.top.color = "#7fb3d8",
    table_body.hlines.color = "#e8e8e8"
  ) |>
  opt_row_striping()
Table 5.2: Characteristics of the National MDS Study population
Table 2. Characteristics of the National MDS Study Population
Comparison across diagnostic categories
By Overall Diagnosis
MDS by IPSS-R Risk
All MDS
(N=613)		 ICUS/IDUS
(N=264)		 CCUS
(N=300)		 P LR-MDS
(N=330)		 HR-MDS
(N=159)		 UNK-MDS
(N=124)		 P
Sex — no. (%)
Female 178 (30%) 123 (50%) 82 (29%) 0.018 94 (30%) 56 (38%) 28 (23%)
Male 407 (70%) 124 (50%) 197 (71%) 221 (70%) 93 (62%) 93 (77%)
Age Group — no. (%)
<60 years 44 (8%) 63 (26%) 19 (7%) <0.001 24 (8%) 17 (11%) 3 (2%) 0.090
60–69 years 116 (20%) 66 (27%) 54 (19%) 63 (20%) 33 (22%) 20 (17%)
70–79 years 274 (47%) 80 (32%) 119 (43%) 142 (45%) 69 (46%) 63 (52%)
80–89 years 131 (22%) 37 (15%) 80 (29%) 75 (24%) 26 (17%) 30 (25%)
≥90 years 20 (3%) 1 (0%) 7 (3%) 11 (3%) 4 (3%) 5 (4%)
Race — no. (%)
White 539 (92%) 211 (85%) 256 (92%) 0.020 293 (93%) 135 (91%) 111 (92%) 0.648
Black or African American 26 (4%) 16 (6%) 6 (2%) 12 (4%) 7 (5%) 7 (6%)
Asian 4 (1%) 7 (3%) 5 (2%) 1 (0%) 1 (1%) 2 (2%)
Ethnicity — no. (%)
Hispanic or Latino 22 (4%) 18 (7%) 9 (3%) 0.027 13 (4%) 3 (2%) 6 (5%) 0.366
Not Hispanic or Latino 544 (93%) 218 (88%) 256 (92%) 290 (92%) 141 (95%) 113 (93%)
Smoking History — no. (%)
Never smoked 250 (43%) 139 (56%) 122 (44%) <0.001 145 (46%) 52 (35%) 53 (44%) 0.118
Smoker 334 (57%) 108 (44%) 157 (56%) 170 (54%) 96 (65%) 68 (56%)
Prior Cancer — no. (%)
No prior cancers 412 (70%) 195 (79%) 199 (71%) 0.082 225 (71%) 101 (68%) 86 (71%) 0.830
Prior cancers (≥1) 173 (30%) 52 (21%) 80 (29%) 90 (29%) 48 (32%) 35 (29%)
P-values from Fisher’s Exact tests (proportions) and Kruskal-Wallis tests (continuous).
LR-MDS: IPSS-R ≤ 3.5; HR-MDS: IPSS-R > 3.5; UNK-MDS: IPSS-R not calculated.

5.3.1 Laboratory Values at Baseline

Show code 
tibble::tribble(
  ~Measure, ~AllMDS, ~ICUS_IDUS, ~CCUS, ~P1,
  ~LR_MDS, ~HR_MDS, ~UNK_MDS, ~P2,

  "Hemoglobin, g/dL",
  "10.1 (8.7\u201311.5)", "11.9 (10.0\u201313.6)", "11.9 (10.3\u201313.5)", "<0.001",
  "10.5 (9.1\u201311.8)", "9.1 (8.0\u201310.2)", "10.1 (8.9\u201311.8)", "<0.001",

  "Platelets, \u00d710\u2079/L",
  "125 (79\u2013219)", "167 (103\u2013248)", "138 (96\u2013195)", "<0.001",
  "139 (91\u2013237)", "84 (53\u2013143)", "135 (82\u2013247)", "<0.001",

  "ANC, \u00d710\u2079/L",
  "1.9 (1.1\u20133.1)", "2.6 (1.6\u20134.1)", "2.9 (1.8\u20134.1)", "<0.001",
  "2.1 (1.3\u20133.2)", "1.1 (0.7\u20132.0)", "2.2 (1.4\u20133.9)", "<0.001",

  "Follow-up time, years",
  "1.6 (0.7\u20133.0)", "1.8 (1.1\u20133.0)", "1.8 (0.9\u20133.3)", "0.054",
  "2.0 (1.0\u20133.9)", "0.9 (0.4\u20131.8)", "1.3 (0.6\u20132.2)", "<0.001"
) |>
  gt() |>
  cols_label(
    Measure = md("**Measure \u2014 median (IQR)**"),
    AllMDS = md("**All MDS**"),
    ICUS_IDUS = md("**ICUS/IDUS**"),
    CCUS = md("**CCUS**"),
    P1 = md("***P***"),
    LR_MDS = md("**LR-MDS**"),
    HR_MDS = md("**HR-MDS**"),
    UNK_MDS = md("**UNK-MDS**"),
    P2 = md("***P***")
  ) |>
  tab_spanner(
    label = md("**By Overall Diagnosis**"),
    columns = c(AllMDS, ICUS_IDUS, CCUS, P1)
  ) |>
  tab_spanner(
    label = md("**MDS by IPSS-R Risk**"),
    columns = c(LR_MDS, HR_MDS, UNK_MDS, P2)
  ) |>
  tab_style(
    style = cell_text(weight = "bold", color = "#922b21"),
    locations = cells_body(columns = c(P1, P2), rows = P1 == "<0.001")
  ) |>
  tab_style(
    style = cell_text(color = "#1a5276"),
    locations = cells_body(columns = c(P1, P2), rows = P1 != "<0.001")
  ) |>
  tab_options(
    table.font.size = px(13),
    table.border.top.color = "#1a5276",
    table.border.top.width = px(3),
    heading.border.bottom.color = "#1a5276",
    column_labels.border.bottom.color = "#1a5276",
    column_labels.border.bottom.width = px(2),
    table_body.hlines.color = "#e8e8e8"
  ) |>
  opt_row_striping()
Table 5.3: Baseline laboratory values by diagnostic category
Measure — median (IQR)
By Overall Diagnosis
MDS by IPSS-R Risk
All MDS ICUS/IDUS CCUS P LR-MDS HR-MDS UNK-MDS P
Hemoglobin, g/dL 10.1 (8.7–11.5) 11.9 (10.0–13.6) 11.9 (10.3–13.5) <0.001 10.5 (9.1–11.8) 9.1 (8.0–10.2) 10.1 (8.9–11.8) <0.001
Platelets, ×10⁹/L 125 (79–219) 167 (103–248) 138 (96–195) <0.001 139 (91–237) 84 (53–143) 135 (82–247) <0.001
ANC, ×10⁹/L 1.9 (1.1–3.1) 2.6 (1.6–4.1) 2.9 (1.8–4.1) <0.001 2.1 (1.3–3.2) 1.1 (0.7–2.0) 2.2 (1.4–3.9) <0.001
Follow-up time, years 1.6 (0.7–3.0) 1.8 (1.1–3.0) 1.8 (0.9–3.3) 0.054 2.0 (1.0–3.9) 0.9 (0.4–1.8) 1.3 (0.6–2.2) <0.001

5.4 Table 3: Cumulative Incidence of Progression

Show code 
tibble::tribble(
  ~RiskGroup, ~Year1, ~Year3, ~Year5,
  "ICUS/IDUS",                       "5 (3\u20138)",      "25 (18\u201332)",   "38 (27\u201350)",
  "CCUS",                            "8 (5\u201311)",     "29 (22\u201335)",   "43 (31\u201355)",
  "MDS: IPSS-R \u2264 1.5",         "13 (7\u201320)",    "49 (39\u201359)",   "63 (51\u201373)",
  "MDS: IPSS-R > 1.5\u20133.0",     "28 (21\u201335)",   "53 (44\u201360)",   "60 (51\u201368)",
  "MDS: IPSS-R > 3.0\u20134.5",     "40 (30\u201350)",   "74 (63\u201383)",   "79 (66\u201387)",
  "MDS: IPSS-R > 4.5\u20136.0",     "54 (38\u201367)",   "79 (60\u201389)",   "79 (60\u201389)",
  "MDS: IPSS-R > 6.0",              "80 (65\u201389)",   "84 (69\u201392)",   "84 (69\u201392)"
) |>
  gt() |>
  cols_label(
    RiskGroup = md("**Risk Group**"),
    Year1 = md("**1-Year**<br>% (95% CI)"),
    Year3 = md("**3-Year**<br>% (95% CI)"),
    Year5 = md("**5-Year**<br>% (95% CI)")
  ) |>
  tab_header(
    title = md("**Table 3. Cumulative Incidence of Progression**"),
    subtitle = md("*Stratified by diagnostic category and IPSS-R score*")
  ) |>
  tab_style(
    style = list(cell_fill(color = "#fdedec"), cell_text(weight = "bold")),
    locations = cells_body(rows = 7)
  ) |>
  tab_style(
    style = cell_fill(color = "#fef9e7"),
    locations = cells_body(rows = 5:6)
  ) |>
  tab_style(
    style = cell_fill(color = "#eafaf1"),
    locations = cells_body(rows = 1:2)
  ) |>
  tab_style(
    style = cell_text(size = px(14)),
    locations = cells_body()
  ) |>
  tab_footnote(
    footnote = "Expanded clinical definition: worsening disease, transfusion dependency, therapy changes, disease-related death."
  ) |>
  tab_options(
    table.font.size = px(13),
    heading.title.font.size = px(17),
    heading.subtitle.font.size = px(13),
    table.border.top.color = "#1a5276",
    table.border.top.width = px(3),
    heading.border.bottom.color = "#1a5276",
    column_labels.border.bottom.color = "#1a5276",
    column_labels.border.bottom.width = px(2),
    table_body.hlines.color = "#e8e8e8",
    table.width = pct(80)
  )
Table 5.4: Cumulative incidence of progression by risk group and IPSS-R strata
Table 3. Cumulative Incidence of Progression
Stratified by diagnostic category and IPSS-R score
Risk Group 1-Year
% (95% CI)		 3-Year
% (95% CI)		 5-Year
% (95% CI)
ICUS/IDUS 5 (3–8) 25 (18–32) 38 (27–50)
CCUS 8 (5–11) 29 (22–35) 43 (31–55)
MDS: IPSS-R ≤ 1.5 13 (7–20) 49 (39–59) 63 (51–73)
MDS: IPSS-R > 1.5–3.0 28 (21–35) 53 (44–60) 60 (51–68)
MDS: IPSS-R > 3.0–4.5 40 (30–50) 74 (63–83) 79 (66–87)
MDS: IPSS-R > 4.5–6.0 54 (38–67) 79 (60–89) 79 (60–89)
MDS: IPSS-R > 6.0 80 (65–89) 84 (69–92) 84 (69–92)
Expanded clinical definition: worsening disease, transfusion dependency, therapy changes, disease-related death.

5.5 Table 4: Disease Progression Types by Baseline Group

Show code 
tibble::tribble(
  ~Category, ~Event, ~ICUS_IDUS, ~CCUS, ~LR_MDS, ~HR_MDS, ~UNK_MDS,

  "Worsening Disease", "Local site re-diagnosis",
  "5 (11.9%)", "5 (7.7%)", "6 (3.5%)", "7 (6.0%)", "3 (5.6%)",

  "Worsening Disease", "Change in ANC",
  "10 (21.7%)", "10 (15.4%)", "33 (19.4%)", "17 (14.7%)", "7 (13.0%)",

  "Worsening Disease", "Change in platelet count",
  "21 (45.7%)", "25 (38.5%)", "33 (19.4%)", "12 (10.3%)", "13 (24.1%)",

  "Worsening Disease", "Change in hemoglobin",
  "2 (4.3%)", "5 (7.7%)", "1 (0.6%)", "1 (0.9%)", "0 (0.0%)",

  "Worsening Disease", "Change in BM blasts",
  "1 (2.2%)", "2 (3.1%)", "19 (11.2%)", "13 (11.2%)", "5 (9.3%)",

  "Disease-Directed Therapy", "End therapy: non-response",
  "0 (0.0%)", "0 (0.0%)", "0 (0.0%)", "1 (0.9%)", "0 (0.0%)",

  "Disease-Directed Therapy", "End therapy: progression",
  "0 (0.0%)", "1 (1.5%)", "6 (3.5%)", "8 (6.9%)", "3 (5.6%)",

  "Disease-Directed Therapy", "New therapy >90d post enrollment",
  "1 (2.2%)", "11 (16.9%)", "43 (25.3%)", "18 (15.5%)", "8 (14.8%)",

  "Disease-Directed Therapy", "New therapy >90d after no therapy",
  "0 (0.0%)", "1 (1.5%)", "0 (0.0%)", "5 (4.3%)", "0 (0.0%)",

  "Disease-Directed Therapy", "Transplant",
  "1 (2.2%)", "0 (0.0%)", "6 (3.5%)", "20 (17.2%)", "3 (5.6%)",

  "Transfusion Dependency", "No \u2192 low dependency",
  "4 (8.7%)", "5 (7.7%)", "15 (8.8%)", "2 (1.7%)", "4 (7.4%)",

  "Transfusion Dependency", "No \u2192 high dependency",
  "0 (0.0%)", "0 (0.0%)", "5 (2.9%)", "1 (0.9%)", "3 (5.6%)",

  "Disease-Related Death", "Disease-related death",
  "1 (2.2%)", "0 (0.0%)", "3 (1.8%)", "11 (9.5%)", "5 (9.3%)",

  "Total", "Total unique individuals progressed",
  "46", "65", "170", "116", "54"
) |>
  gt(groupname_col = "Category") |>
  cols_label(
    Event = md("**Progression Event**"),
    ICUS_IDUS = md("**ICUS/IDUS**<br>(N=247)"),
    CCUS = md("**CCUS**<br>(N=279)"),
    LR_MDS = md("**LR-MDS**<br>(N=315)"),
    HR_MDS = md("**HR-MDS**<br>(N=149)"),
    UNK_MDS = md("**UNK-MDS**<br>(N=121)")
  ) |>
  tab_header(
    title = md("**Table 4. Disease Progression Types by Baseline Disease Group**"),
    subtitle = md("*Index progression events \u2014 n (% of those who progressed)*")
  ) |>
  tab_style(
    style = list(cell_fill(color = "#eaf2fa"), cell_text(weight = "bold")),
    locations = cells_row_groups()
  ) |>
  tab_style(
    style = list(
      cell_fill(color = "#1a5276"),
      cell_text(color = "white", weight = "bold", size = px(13))
    ),
    locations = cells_body(rows = Event == "Total unique individuals progressed")
  ) |>
  tab_style(
    style = cell_text(size = px(12)),
    locations = cells_body()
  ) |>
  tab_footnote(
    footnote = "Percentages represent proportion of progressed patients within each diagnostic group."
  ) |>
  tab_options(
    table.font.size = px(12),
    heading.title.font.size = px(17),
    heading.subtitle.font.size = px(13),
    table.border.top.color = "#1a5276",
    table.border.top.width = px(3),
    heading.border.bottom.color = "#1a5276",
    column_labels.border.bottom.color = "#1a5276",
    column_labels.border.bottom.width = px(2),
    row_group.border.top.color = "#7fb3d8",
    table_body.hlines.color = "#e8e8e8"
  ) |>
  opt_row_striping()
Table 5.5: Index progression events by category and baseline diagnosis
Table 4. Disease Progression Types by Baseline Disease Group
Index progression events — n (% of those who progressed)
Progression Event ICUS/IDUS
(N=247)		 CCUS
(N=279)		 LR-MDS
(N=315)		 HR-MDS
(N=149)		 UNK-MDS
(N=121)
Worsening Disease
Local site re-diagnosis 5 (11.9%) 5 (7.7%) 6 (3.5%) 7 (6.0%) 3 (5.6%)
Change in ANC 10 (21.7%) 10 (15.4%) 33 (19.4%) 17 (14.7%) 7 (13.0%)
Change in platelet count 21 (45.7%) 25 (38.5%) 33 (19.4%) 12 (10.3%) 13 (24.1%)
Change in hemoglobin 2 (4.3%) 5 (7.7%) 1 (0.6%) 1 (0.9%) 0 (0.0%)
Change in BM blasts 1 (2.2%) 2 (3.1%) 19 (11.2%) 13 (11.2%) 5 (9.3%)
Disease-Directed Therapy
End therapy: non-response 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.9%) 0 (0.0%)
End therapy: progression 0 (0.0%) 1 (1.5%) 6 (3.5%) 8 (6.9%) 3 (5.6%)
New therapy >90d post enrollment 1 (2.2%) 11 (16.9%) 43 (25.3%) 18 (15.5%) 8 (14.8%)
New therapy >90d after no therapy 0 (0.0%) 1 (1.5%) 0 (0.0%) 5 (4.3%) 0 (0.0%)
Transplant 1 (2.2%) 0 (0.0%) 6 (3.5%) 20 (17.2%) 3 (5.6%)
Transfusion Dependency
No → low dependency 4 (8.7%) 5 (7.7%) 15 (8.8%) 2 (1.7%) 4 (7.4%)
No → high dependency 0 (0.0%) 0 (0.0%) 5 (2.9%) 1 (0.9%) 3 (5.6%)
Disease-Related Death
Disease-related death 1 (2.2%) 0 (0.0%) 3 (1.8%) 11 (9.5%) 5 (9.3%)
Total
Total unique individuals progressed 46 65 170 116 54
Percentages represent proportion of progressed patients within each diagnostic group.

5.6 Table 5: Clinical Monitoring Recommendations

Show code 
tibble::tribble(
  ~Feature, ~ICUS, ~IDUS, ~CCUS, ~LR_MDS, ~HR_MDS,

  "Cytopenias",
  "\u2713", "\u2014", "\u2713", "\u2713", "\u2713",

  "Dysplasia",
  "\u2014", "\u2713", "\u2014", "\u2713", "\u2713",

  "Clonality",
  "\u2014", "\u2014", "\u2713", "\u2713", "\u2713",

  "Risk of transformation",
  "\u2191", "\u2191", "\u2191\u2191", "\u2191\u2191\u2191", "\u2191\u2191\u2191\u2191\u2191",

  "CBC monitoring",
  "1\u20132\u00d7/year",
  "1\u20132\u00d7/year",
  "2\u20134\u00d7/year",
  "4\u20138\u00d7/year; increase as treatment starts",
  "With active therapy and treatment",

  "NGS approach",
  "Every 1.5\u20132 years; repeat at increased interval if platelets \u2193\u226550% or Hg \u2193\u22651.5 g",
  "Every 1.5\u20132 years; repeat at increased interval if platelets \u2193\u226550% or Hg \u2193\u22651.5 g",
  "Every 1\u20131.5 years; consider earlier interval with mutations of increased progression rates",
  "Every 1\u20131.5 years; repeat with clinical need for new therapy; consider earlier with high-risk mutations",
  "With disease change; pre-BMT; repeat with clinical need for new therapy",

  "BM approach",
  "Pending count decline; repeat warranted for declining counts suggesting worsening disease",
  "Pending count decline; repeat warranted for declining counts suggesting worsening disease",
  "Every other year; consider earlier with high-risk mutations or adverse prognostic significance",
  "1\u20132\u00d7/year pending mutations (SF3B1 may not require if anemia progression alone); consider earlier with adverse mutations",
  "1\u20132\u00d7/year; consider earlier with mutations of increased progression rates or adverse prognostic significance",

  "Clinical approach",
  "Observation; driven by risk of progression metrics",
  "Observation",
  "Observation",
  "Observation vs clinical trial; interventions to alleviate cytopenia symptoms; HMA/BMT for later/refractory stages",
  "Clinical trials; HMA/BMT"
) |>
  gt() |>
  cols_label(
    Feature = md("**Feature**"),
    ICUS = md("**ICUS**"),
    IDUS = md("**IDUS**"),
    CCUS = md("**CCUS**"),
    LR_MDS = md("**LR-MDS**"),
    HR_MDS = md("**HR-MDS**")
  ) |>
  tab_header(
    title = md("**Table 5. Considerations for Clinical Monitoring by Diagnosis**"),
    subtitle = md("*Surveillance recommendations from the MDS NHS steering committee*")
  ) |>
  # Risk of transformation row: color-coded

  tab_style(
    style = list(cell_fill(color = "#fdedec"), cell_text(weight = "bold")),
    locations = cells_body(columns = HR_MDS, rows = Feature == "Risk of transformation")
  ) |>
  tab_style(
    style = cell_fill(color = "#eafaf1"),
    locations = cells_body(columns = c(ICUS, IDUS), rows = Feature == "Risk of transformation")
  ) |>
  tab_style(
    style = cell_fill(color = "#fef9e7"),
    locations = cells_body(columns = CCUS, rows = Feature == "Risk of transformation")
  ) |>
  tab_style(
    style = cell_fill(color = "#fdf2e9"),
    locations = cells_body(columns = LR_MDS, rows = Feature == "Risk of transformation")
  ) |>
  # Bold the first 4 feature rows
  tab_style(
    style = list(cell_fill(color = "#f8f9f9"), cell_text(weight = "bold", size = px(13))),
    locations = cells_body(
      rows = Feature %in% c("Cytopenias", "Dysplasia", "Clonality", "Risk of transformation")
    )
  ) |>
  tab_style(
    style = cell_text(size = px(12)),
    locations = cells_body(
      rows = !(Feature %in% c("Cytopenias", "Dysplasia", "Clonality", "Risk of transformation"))
    )
  ) |>
  cols_width(
    Feature ~ px(140),
    ICUS ~ px(160),
    IDUS ~ px(160),
    CCUS ~ px(190),
    LR_MDS ~ px(220),
    HR_MDS ~ px(190)
  ) |>
  tab_footnote(
    footnote = "BM = bone marrow; BMT = bone marrow transplant; HMA = hypomethylating agents; NGS = next-generation sequencing."
  ) |>
  tab_options(
    table.font.size = px(12),
    heading.title.font.size = px(17),
    heading.subtitle.font.size = px(13),
    table.border.top.color = "#1a5276",
    table.border.top.width = px(3),
    heading.border.bottom.color = "#1a5276",
    column_labels.border.bottom.color = "#1a5276",
    column_labels.border.bottom.width = px(2),
    table_body.hlines.color = "#e8e8e8"
  )
Table 5.6: Recommendations for clinical monitoring by diagnosis
Table 5. Considerations for Clinical Monitoring by Diagnosis
Surveillance recommendations from the MDS NHS steering committee
Feature ICUS IDUS CCUS LR-MDS HR-MDS
Cytopenias ✓ — ✓ ✓ ✓
Dysplasia — ✓ — ✓ ✓
Clonality — — ✓ ✓ ✓
Risk of transformation ↑ ↑ ↑↑ ↑↑↑ ↑↑↑↑↑
CBC monitoring 1–2×/year 1–2×/year 2–4×/year 4–8×/year; increase as treatment starts With active therapy and treatment
NGS approach Every 1.5–2 years; repeat at increased interval if platelets ↓≥50% or Hg ↓≥1.5 g Every 1.5–2 years; repeat at increased interval if platelets ↓≥50% or Hg ↓≥1.5 g Every 1–1.5 years; consider earlier interval with mutations of increased progression rates Every 1–1.5 years; repeat with clinical need for new therapy; consider earlier with high-risk mutations With disease change; pre-BMT; repeat with clinical need for new therapy
BM approach Pending count decline; repeat warranted for declining counts suggesting worsening disease Pending count decline; repeat warranted for declining counts suggesting worsening disease Every other year; consider earlier with high-risk mutations or adverse prognostic significance 1–2×/year pending mutations (SF3B1 may not require if anemia progression alone); consider earlier with adverse mutations 1–2×/year; consider earlier with mutations of increased progression rates or adverse prognostic significance
Clinical approach Observation; driven by risk of progression metrics Observation Observation Observation vs clinical trial; interventions to alleviate cytopenia symptoms; HMA/BMT for later/refractory stages Clinical trials; HMA/BMT
BM = bone marrow; BMT = bone marrow transplant; HMA = hypomethylating agents; NGS = next-generation sequencing.

5.7 Key Findings Summary

Show code 
tibble::tribble(
  ~Group, ~AnnualRate, ~FiveYearCum, ~KeyPredictors,

  "HR-MDS (IPSS-R > 3.5)",
  "~23%", "79\u201384%",
  "TP53 mutation; higher mutation number; poor/very poor cytogenetic score",

  "LR-MDS (IPSS-R \u2264 3.5)",
  "~15%", "60\u201363%",
  "TP53, ASXL1, IDH2 mutations; higher mutation number; female sex",

  "CCUS",
  "~7%", "43%",
  "Higher quantity of mutations",

  "ICUS/IDUS",
  "~7%", "38%",
  "Higher platelet count"
) |>
  gt() |>
  cols_label(
    Group = md("**Diagnostic Group**"),
    AnnualRate = md("**Annual Progression Rate**"),
    FiveYearCum = md("**5-Year Cumulative Incidence**"),
    KeyPredictors = md("**Significant Predictors of Progression**")
  ) |>
  tab_header(
    title = md("**Key Findings: Progression Rates and Predictors**"),
    subtitle = md("*Using refined clinical definitions from the MDS NHS*")
  ) |>
  tab_style(
    style = list(cell_fill(color = "#fdedec"), cell_text(weight = "bold")),
    locations = cells_body(rows = 1)
  ) |>
  tab_style(
    style = cell_fill(color = "#fef9e7"),
    locations = cells_body(rows = 2)
  ) |>
  tab_style(
    style = cell_fill(color = "#eafaf1"),
    locations = cells_body(rows = 3:4)
  ) |>
  tab_options(
    table.font.size = px(14),
    heading.title.font.size = px(17),
    heading.subtitle.font.size = px(13),
    table.border.top.color = "#1a5276",
    table.border.top.width = px(3),
    heading.border.bottom.color = "#1a5276",
    column_labels.border.bottom.color = "#1a5276",
    column_labels.border.bottom.width = px(2),
    table_body.hlines.color = "#d5d8dc",
    table.width = pct(92)
  )
Table 5.7: Summary of key annual progression rates and predictors
Key Findings: Progression Rates and Predictors
Using refined clinical definitions from the MDS NHS
Diagnostic Group Annual Progression Rate 5-Year Cumulative Incidence Significant Predictors of Progression
HR-MDS (IPSS-R > 3.5) ~23% 79–84% TP53 mutation; higher mutation number; poor/very poor cytogenetic score
LR-MDS (IPSS-R ≤ 3.5) ~15% 60–63% TP53, ASXL1, IDH2 mutations; higher mutation number; female sex
CCUS ~7% 43% Higher quantity of mutations
ICUS/IDUS ~7% 38% Higher platelet count
NoteCitation

DeZern AE, Gillis N, Otterstatter M, et al. A novel approach to defining progression in MDS and precursor myeloid conditions in The MDS Natural History Study. Blood Advances. 2025. Tracking no: ADV-2025-018770R1. NCT02775383.