# Myelodysplastic syndromes / neoplasms (MDS)

Source: https://onco.cc/cancers/mds/  
OnCo record `mds` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Bone-marrow disorders where blood cells are made badly and too few reach the blood; a third progress to acute leukaemia. Treatment ranges from transfusions and growth factors to hypomethylating drugs and, for the fit, transplant.

## Summary

MDS are clonal myeloid neoplasms with ineffective haematopoiesis, cytopenias, dysplasia and variable risk of transformation to AML. Risk is stratified by IPSS-R and, since 2022, the molecular IPSS-M, which incorporates mutations (TP53 multi-hit, ASXL1, RUNX1, SF3B1 among 31 genes). The WHO 2022 and ICC classifications define genetically specified entities (SF3B1-mutant, del(5q), biallelic TP53) and renamed the group 'myelodysplastic neoplasms'.

Lower-risk disease is treated for anaemia: erythropoiesis-stimulating agents, lenalidomide for del(5q), luspatercept (MEDALIST 2020, COMMANDS 2023 first line), and imetelstat (IMerge, 2024) after ESA failure. Higher-risk disease is treated with hypomethylating agents (azacitidine, decitabine, oral decitabine-cedazuridine) and, for the fit with a donor, allogeneic transplant, the only cure. Three large phase 3 additions to azacitidine failed in 2023-24 (magrolimab ENHANCE, sabatolimab STIMULUS-MDS2, venetoclax VERONA), leaving azacitidine alone as the higher-risk standard.

Open problems: TP53-mutant MDS, post-HMA failure (median survival under six months), and how to use IPSS-M to time transplant.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; haematologic
- Group: haematologic
- Burden: MDS affects around 4-5 per 100,000 people per year overall, rising steeply with age (median age ~70), according to SEER.
- Subtypes: MDS with low blasts (MDS-LB); MDS with SF3B1 mutation (ring sideroblasts); MDS with del(5q); MDS with biallelic TP53 inactivation; MDS with increased blasts (IB1, IB2); Hypoplastic MDS; Therapy-related MDS
- Biomarkers: IPSS-R and IPSS-M risk; Cytogenetics (del(5q), -7, complex karyotype); NGS panel (SF3B1, TP53, ASXL1, RUNX1, TET2, DNMT3A, SRSF2, U2AF1); Blast percentage; Serum EPO level (ESA response prediction); Transfusion burden

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/mds/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/mds/#overview [2 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/mds/#what-it-is [9 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/mds/#finding-it [6 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/mds/#treating-it [4 settings, 1 regimen, 4 decisions with options]
- Evidence (own page): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/mds/evidence/ [33 trials, 3 key papers, 9 milestones]
- The science (own page): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/mds/science/ [45 targets, 5 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/mds/where-you-are/ [5 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/mds/#living-with-it [18 questions, 5 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/mds/coming/ [22 medicines, 33 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/mds/data/ [181 connected records]

## Standard of care

- Lower risk, anaemia: ESA if serum EPO <500; luspatercept first line (COMMANDS) or after ESA failure (MEDALIST); imetelstat after ESA failure (IMerge); lenalidomide for del(5q). ([Luspatercept](https://onco.cc/drugs/luspatercept/), [Imetelstat](https://onco.cc/drugs/imetelstat/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/))
- Higher risk, transplant candidate: Allogeneic HSCT, usually after hypomethylating-agent cytoreduction; BMT CTN 1102 showed a survival benefit for transplant in 50-75-year-olds. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [BMT CTN 1102](https://onco.cc/trials/bmt-ctn-1102/))
- Higher risk, not transplant candidate: Azacitidine (AZA-001) or decitabine / oral decitabine-cedazuridine until progression; supportive care and trials. ([Azacitidine](https://onco.cc/drugs/azacitidine/), [Decitabine + cedazuridine (oral)](https://onco.cc/drugs/decitabine-cedazuridine/))
- Supportive care, all risks: Transfusion, iron chelation for transfusional iron overload (TELESTO), infection management, G-CSF for neutropenic infection. ([Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/), [Growth factors: G-CSF and febrile neutropenia prevention](https://onco.cc/technologies/g-csf-growth-factors/), [TELESTO](https://onco.cc/trials/telesto/))

## State of the art

- IPSS-M (2022) reclassifies about half of patients relative to IPSS-R and is now the recommended risk model.
- Two new drugs for lower-risk anaemia in four years: luspatercept and imetelstat, both reducing transfusion dependence.
- Higher-risk MDS has had no new drug since azacitidine: the 2023-24 failures of magrolimab, sabatolimab and venetoclax combinations were a field-wide setback.
- Allogeneic transplant remains the only cure; reduced-intensity conditioning extends it to older patients.

## Open problems

- No drug has beaten azacitidine in higher-risk MDS.
- TP53-mutant and complex-karyotype disease: median survival about a year even after transplant.
- Clonal cytopenia of undetermined significance (CCUS): who to watch, who to treat.
- Post-HMA failure has no standard.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Myelodysplastic_syndrome
- IPSS-M (NEJM Evidence 2022): https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200008
- NCI PDQ: MDS: https://www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq

## Connected records

- cancers: [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Higher-risk myelodysplastic syndromes](https://onco.cc/cancers/mds-higher-risk/), [Lower-risk myelodysplastic syndromes](https://onco.cc/cancers/mds-lower-risk/), [Systemic mastocytosis](https://onco.cc/cancers/systemic-mastocytosis/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [CD47 and SIRP-alpha blockade](https://onco.cc/technologies/cd47-blockade/), [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/), [Ex vivo drug sensitivity screening in blood cancers (EXALT)](https://onco.cc/technologies/functional-precision-medicine-haematology/), [Growth factors: G-CSF and febrile neutropenia prevention](https://onco.cc/technologies/g-csf-growth-factors/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/), [TIM-3 blockade](https://onco.cc/technologies/tim3-blockade/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/)
- targets: [ASXL1](https://onco.cc/targets/asxl1/), [BCL-2](https://onco.cc/targets/bcl2/), [BCOR](https://onco.cc/targets/bcor/), [CD47](https://onco.cc/targets/cd47/), [CDA](https://onco.cc/targets/cda/), [Cereblon (CRBN)](https://onco.cc/targets/cereblon/), [CUL4A](https://onco.cc/targets/cul4a/), [DDB1](https://onco.cc/targets/ddb1/), [DDX41](https://onco.cc/targets/ddx41/), [DNA methyltransferase 3A (DNMT3A)](https://onco.cc/targets/dnmt3a/), [DNMT1 (DNA methyltransferase 1)](https://onco.cc/targets/dnmt1/), [ETV6](https://onco.cc/targets/etv6/), [FANCC](https://onco.cc/targets/fancc/), [GATA2](https://onco.cc/targets/gata2/), [KIR2DL1 (inhibitory KIR)](https://onco.cc/targets/kir2dl1/), [MPL (thrombopoietin receptor)](https://onco.cc/targets/mpl/), [MT-CO1](https://onco.cc/targets/mt-co1/), [MYSM1](https://onco.cc/targets/mysm1/), [POLA2](https://onco.cc/targets/pola2/), [POLD2](https://onco.cc/targets/pold2/), [POLD3](https://onco.cc/targets/pold3/), [POLD4](https://onco.cc/targets/pold4/), [POLE2](https://onco.cc/targets/pole2/), [POLE3](https://onco.cc/targets/pole3/), [PRIM1](https://onco.cc/targets/prim1/), [PRIM2](https://onco.cc/targets/prim2/), [RBX1](https://onco.cc/targets/rbx1/), [RRM2](https://onco.cc/targets/rrm2/), [RRM2B](https://onco.cc/targets/rrm2b/), [RUNX1](https://onco.cc/targets/runx1/), [SAMD9](https://onco.cc/targets/samd9/), [SAMD9L](https://onco.cc/targets/samd9l/), [SETBP1](https://onco.cc/targets/setbp1/), [SF3B1](https://onco.cc/targets/sf3b1/), [SH2B3](https://onco.cc/targets/sh2b3/), [SLX4](https://onco.cc/targets/slx4/), [SRSF2](https://onco.cc/targets/srsf2/), [TGFB1](https://onco.cc/targets/tgfb1/), [TGFB2](https://onco.cc/targets/tgfb2/), [TGFB3](https://onco.cc/targets/tgfb3/), [TIM-3](https://onco.cc/targets/tim3/), [TP53](https://onco.cc/targets/tp53/), [U2AF1](https://onco.cc/targets/u2af1/)
- drugs: [Allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq](https://onco.cc/drugs/tregzi/), [ARD103](https://onco.cc/drugs/ard103/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [Belumosudil](https://onco.cc/drugs/belumosudil/), [Bexmarilimab](https://onco.cc/drugs/bexmarilimab/), [Decitabine](https://onco.cc/drugs/decitabine/), [Decitabine + cedazuridine (oral)](https://onco.cc/drugs/decitabine-cedazuridine/), [Dorocubicel (UM171-expanded cord blood)](https://onco.cc/drugs/dorocubicel/), [Elritercept](https://onco.cc/drugs/elritercept/), [Eltrombopag](https://onco.cc/drugs/eltrombopag/), [Imetelstat](https://onco.cc/drugs/imetelstat/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Luspatercept](https://onco.cc/drugs/luspatercept/), [Magrolimab](https://onco.cc/drugs/magrolimab/), [Omidubicel](https://onco.cc/drugs/omidubicel/), [Ravulizumab](https://onco.cc/drugs/ravulizumab/), [Romiplostim](https://onco.cc/drugs/romiplostim/), [Sabatolimab](https://onco.cc/drugs/sabatolimab/), [Spartalizumab](https://onco.cc/drugs/spartalizumab/), [Treosulfan](https://onco.cc/drugs/treosulfan/), [Tuspetinib](https://onco.cc/drugs/tuspetinib/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- companies: [Aprea Therapeutics](https://onco.cc/companies/aprea-therapeutics/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Disc Medicine](https://onco.cc/companies/disc-medicine/), [Ellipses Pharma](https://onco.cc/companies/ellipses-pharma/), [Gamida Cell](https://onco.cc/companies/gamida-cell/), [Geron Corporation](https://onco.cc/companies/geron/), [Gilead Sciences (incl. Kite)](https://onco.cc/companies/gilead/), [medac](https://onco.cc/companies/medac/), [Novartis](https://onco.cc/companies/novartis/), [Orca Bio](https://onco.cc/companies/orca-bio/), [Otsuka Pharmaceutical](https://onco.cc/companies/otsuka/), [Ryvu Therapeutics](https://onco.cc/companies/ryvu-therapeutics/), [Shenzhen TargetRx](https://onco.cc/companies/shenzhen-targetrx/), [Taiho Pharmaceutical (Otsuka)](https://onco.cc/companies/taiho/), [Treadwell Therapeutics](https://onco.cc/companies/treadwell-therapeutics/)
- pathways: [CD47 / SIRPα (the 'don't eat me' signal)](https://onco.cc/pathways/cd47-sirpa/), [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [Mutant IDH / 2-hydroxyglutarate](https://onco.cc/pathways/idh-2hg/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- terms: [Ageing tissue and clonal fields: cancer as a disease of old tissue](https://onco.cc/terms/ageing-tissue-field-theory/), [Anaemia](https://onco.cc/terms/anaemia/), [Blasts (leukaemic blast cells)](https://onco.cc/terms/blasts/), [Cytopenias and myelosuppression](https://onco.cc/terms/cytopenias/), [Differentiation syndrome](https://onco.cc/terms/differentiation-syndrome/), [ELN 2022 risk classification](https://onco.cc/terms/eln-risk/), [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [Hypomethylating agents (azacitidine, decitabine)](https://onco.cc/terms/hma/), [Immunomodulatory drugs (IMiDs) and CELMoDs](https://onco.cc/terms/imid/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Secondary malignancy (therapy-related cancer)](https://onco.cc/terms/secondary-malignancy/)
- trials: [A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies](https://onco.cc/trials/nct05589896/), [A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study)](https://onco.cc/trials/nct04256317/), [A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia](https://onco.cc/trials/nct05883956/), [A Study of BGB-11417 in Participants With Myeloid Malignancies](https://onco.cc/trials/nct04771130/), [A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes](https://onco.cc/trials/nct05732103/), [A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular B](https://onco.cc/trials/nct06499285/), [A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies](https://onco.cc/trials/nct05428969/), [A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials](https://onco.cc/trials/nct04064060/), [AZA-001](https://onco.cc/trials/aza-001/), [BMT CTN 1102](https://onco.cc/trials/bmt-ctn-1102/), [Clinical Study of ARD103 CAR-T Therapy for Patients With R/R AML or MDS](https://onco.cc/trials/nct06680752/), [Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia](https://onco.cc/trials/nct03850574/), [Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia](https://onco.cc/trials/nct00003436/), [COMMANDS](https://onco.cc/trials/commands/), [First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult Patients](https://onco.cc/trials/nct05601726/), [IMerge](https://onco.cc/trials/imerge/), [Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)](https://onco.cc/trials/nct04313881/), [MEDALIST](https://onco.cc/trials/medalist/), [PBSS1113 in Combination With Azacitidine to Treat Patients With AML/MDS](https://onco.cc/trials/nct07761533/), [Precision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies](https://onco.cc/trials/nct05316701/), [Roll-over Study for Patients Who Have Completed a Prior Novartis-sponsored Sabatolimab (MBG453) Study and Are Judged by the Investigator to Benefit From Continued Treatment With Sabatolimab.](https://onco.cc/trials/nct05201066/), [RVU120 for Treatment of Anemia in Patients With Lower-risk Myelodysplastic Neoplasms](https://onco.cc/trials/nct06243458/), [Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant](https://onco.cc/trials/nct01744223/), [Study of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression](https://onco.cc/trials/nct07155226/), [Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia](https://onco.cc/trials/nct05320198/), [Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant](https://onco.cc/trials/nct03301168/), [Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)](https://onco.cc/trials/nct05308264/), [Study to Evaluate Imetelstat in Patients With High-Risk MDS or AML Failing HMA-based Therapy](https://onco.cc/trials/nct05583552/), [Study to Evaluate the Safety and Tolerability of EP0042](https://onco.cc/trials/nct04581512/), [TELESTO](https://onco.cc/trials/telesto/), [TGRX-814 Chinese Phase I/II in Patients With Hematological Malignancies](https://onco.cc/trials/nct06206174/), [Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome](https://onco.cc/trials/nct07216443/), [VERONA](https://onco.cc/trials/verona/)
- people: [Amer M. Zeidan](https://onco.cc/people/amer-zeidan/), [Marc H.G.P. Raaijmakers](https://onco.cc/people/marc-raaijmakers/), [Pierre Fenaux](https://onco.cc/people/pierre-fenaux/), [Uwe Platzbecker](https://onco.cc/people/uwe-platzbecker/)
- journals: [Clinical lymphoma, myeloma & leukemia](https://onco.cc/journals/clinical-lymphoma-myeloma-and-leukemia/), [Current hematologic malignancy reports](https://onco.cc/journals/current-hematologic-malignancy-reports/), [Leukemia & lymphoma](https://onco.cc/journals/leukemia-and-lymphoma/), [Leukemia research](https://onco.cc/journals/leukemia-research/)
- collections: [Leukemia & Lymphoma Society (LLS)](https://onco.cc/collections/leukemia-lymphoma-society/)
- key papers: [BMT CTN 1102: biologic assignment trial of reduced-intensity transplant by donor availability in patients aged 50 to 75 with advanced myelodysplastic syndrome](https://onco.cc/key-papers/paper-bmt-ctn-1102-transplant-older-mds-nakamura-jco-2021/), [COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions](https://onco.cc/key-papers/paper-commands-luspatercept-mds-lancet-2023/), [IMerge: imetelstat, a telomerase inhibitor, for transfusion-dependent lower-risk MDS after erythropoietin has failed](https://onco.cc/key-papers/paper-imerge-imetelstat-mds-lancet-2024/)
- institutions: [Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences](https://onco.cc/institutions/cams-hematology/), [Leipzig University Hospital / University Cancer Center Leipzig (UCCL)](https://onco.cc/institutions/university-hospital-leipzig/), [Montefiore Einstein Comprehensive Cancer Center](https://onco.cc/institutions/montefiore-einstein/), [Sylvester Comprehensive Cancer Center, University of Miami](https://onco.cc/institutions/sylvester-miami/), [USC Norris Comprehensive Cancer Center](https://onco.cc/institutions/usc-norris/)
- biomarkers: [IDH1 R132 mutation](https://onco.cc/biomarkers/idh1-r132/), [TP53 mutation and del(17p)](https://onco.cc/biomarkers/tp53-del17p/)

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JSON: https://onco.cc/api/v1/entities/mds.json