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Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies characterized by multilineage cytopenias, including anemia1

The World Health Organization (WHO) classifies MDS as neoplastic and therefore cancer2

  • MDS are characterized by:
    • Bone marrow dysfunction2,3
    • Dysplasia2,3
    • Genomic instability2
    • Peripheral blood cytopenia2,3
    • Ineffective hematopoiesis3

Anemia is present in the majority of patients with MDS1

  • At diagnosis, anemia is the most common cytopenia present in patients with MDS1*
  • 94% of patients with MDS received red blood cell (RBC) transfusions in the SEER-Sound registry of 783 patients from 2001 to 20074
    • 13% of all patients with MDS requiring RBC transfusions had ring sideroblasts4

*Determined in a database analysis of 7012 patients with untreated MDS from 11 countries for the International Working Group for the Prognosis of MDS (IWG-PM) project.1

Based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), MDS management approaches differ according to MDS subtype and severity of disease5

Patients with MDS may also have ring sideroblasts6

23% to 33% of patients with MDS have ring sideroblasts.
23% to 33% of patients with MDS have ring

Ring sideroblasts are part of the WHO 2016 classification of MDS7

  • The WHO 2016 recognizes 2 MDS subtypes specific to ring sideroblasts7:
    • MDS-RS with single lineage dysplasia (MDS-RS-SLD)
    • MDS-RS with multilineage dysplasia (MDS-RS-MLD)
  • MDS-RS subtype is identified with <5% bone marrow blasts and either7:
    • ≥15% ring sideroblasts in the bone marrow
    • ≥5% ring sideroblasts in the bone marrow and the presence of an SF3B1 mutation (identified through molecular testing)
  • MDS-RS is recognized as part of the ICD-10-CM coding system8
  • Ring sideroblasts may also be present at any level in other subtypes of MDS9
  • MDS/MPN-RS-T is a rare subtype recognized by the WHO 2016. It has similarities to MDS-RS but is characterized by specific clinical features7,10
    • These include anemia, bone marrow dysplasia with ring sideroblasts, and persistent thrombocytosis ≥450 x 109/L with proliferation of large and morphologically atypical megakaryocytes7

ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification.

Ring sideroblasts are erythroblasts with iron-loaded mitochondria associated with anemia9

Ring sideroblasts are erythroblasts with iron-loaded mitochondria associated with anemia.
Ring sideroblasts are erythroblasts with iron-loaded
mitochondria associated with anemia.

For illustrative purposes only.

  • Ring sideroblasts are identified by iron staining and the results can be found on pathology reports9
  • There is variability in how pathologists describe the presence of ring sideroblasts in pathology reports11

Consult with your pathologist about how ring sideroblasts are reported in your patients with MDS

The IPSS-R categorization is the preferred* prognostic system of the NCCN Guidelines®5

The majority of patients with MDS have IPSS-R very low- to intermediate-risk disease at diagnosis1

Distribution of patients with MDS by IPSS-R risk status (N = 7012)

The majority of patients with MDS have IPSS-R very
low- to intermediate-risk disease at diagnosis.
The majority of patients with MDS have IPSS-R very
low- to intermediate-risk disease at diagnosis.

*The NCCN Guidelines for MDS also note that other risk stratification systems have good value.5

Distribution of the IPSS-R risk scores at time of diagnosis evaluated in the recently diagnosed patient cohort; (N = 7012) for the patient population included in the IPSS-R analysis.1

IPSS-R, Revised International Prognostic Scoring System.

IPSS-R is based on bone marrow cytogenetics, marrow blast percentage, and presence and depth of cytopenias1

Prognostic score values1
Prognostic variable BM blasts, % Cytogenetics Hgb, g/dL Platelets, x 109 cells/L ANC, x 109 cells/L
0 ≤2 Very good ≥10 ≥100 ≥0.8
0.5 50 to <100 <0.8
1 >2 to <5 Good 8 to <10 <50
1.5 <8
2 5 to 10 Intermediate
3 >10 Poor
4 Very poor

IPSS-R prognostic risk categories/scores1
Very low Low Intermediate High Very high
≤1.5 >1.5–3 >3–4.5 >4.5–6 >6

ANC, absolute neutrophil count; BM, bone marrow; Hgb, hemoglobin.

An IPSS-R score is calculated by adding the values for the prognostic factors together

An example of an IPSS-R low-risk score:

Ineffective erythropoiesis is an underlying cause of anemia in MDS12

Anemia in MDS is linked to bone marrow dysfunction characterized as ineffective erythropoiesis13

  • In MDS, stem cells lack the ability for differentiation and maturation, resulting in bone marrow dysfunction and poor blood cell production, in particular RBCs

Ineffective erythropoiesis in MDS may lead to anemia requiring RBC transfusions, and is characterized by12,14:

  • Increased proliferation of erythroid progenitors

  • Increased death of erythroid precursors

  • Impaired erythroid maturation

The presence of anemia despite increased proliferation of progenitor cells is indicative of ineffective erythropoiesis in MDS

There is a need to help address anemia due to ineffective erythropoiesis in patients with MDS requiring RBC transfusions



REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

REBLOZYL is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).

REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.




In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.


Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 1.8% to 8.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In adult patients with MDS with normal baseline blood pressure, 26 (29.9%) patients developed SBP ≥130 mm Hg and 23 (16.4%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Embryo-Fetal Toxicity

REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.



  • Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML)
  • Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%)

Myelodysplastic Syndromes

  • Grade ≥3 (≥2%) adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. A fatal adverse reaction occurred in 5 (2.1%) patients
  • The most common (≥10%) adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection


It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.

Please click here for full Prescribing Information for REBLOZYL.

References: 1. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. 2. Steensma DP, Komrokji RS, Stone RM, et al. Disparity in perceptions of disease characteristics, treatment effectiveness, and factors influencing treatment adherence between physicians and patients with myelodysplastic syndromes. Cancer. 2014;120(11):1670-1676. 3. Varney ME, Melgar K, Niederkorn M, Smith M, Barreyro L, Starczynowski DT. Deconstructing innate immune signaling in myelodysplastic syndromes. Exp Hematol. 2015;43(8):587-598. 4. Ramsey SD, McCune JS, Blough DK, et al. Patterns of blood product use among patients with myelodysplastic syndrome. Vox Sang. 2012;102(4):331-337. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myelodysplastic Syndromes V.1.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed September 11, 2020. To view the most recent and complete version of the guideline, go online to NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616-3627. 7. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. 8. US Government Printing Office. The International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM): D-46.B refractory cytopenia with multilineage dysplasia and ring sideroblasts. Accessed March 10, 2020. 9. Malcovati L, Cazzola M. Recent advances in the understanding of myelodysplastic syndromes with ring sideroblasts. Br J Haematol. 2016;174(6):847-858. 10. Aoyama Y, Sakai K, Kodaka T, et al. Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN with RS-T) complicated by hyperleukocytosis and gene analysis in relation to leukocytosis. J Clin Exp Hematop. 2019;59(1):29-33. 11. Sever C, Abbott CL, de Baca ME. Bone marrow synoptic reporting for hematologic neoplasms: guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2016;140(9):932-949. 12. Santini V. Anemia as the main manifestation of myelodysplastic syndromes. Semin Hematol. 2015;52(4):348-356. 13. Cazzola M, Malcovati L. Myelodysplastic syndromes—coping with ineffective hematopoiesis. N Engl J Med. 2005;352(6):536-538. 14. Fontenay-Roupie M, Bouscary D, Guesnu M, et al. Ineffective erythropoiesis in myelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction. Br J Haematol. 1999;106(2):464-473.