Impact of Anemia in Myelodysplastic Syndromes (MDS)

Anemia is the most common cytopenia found in MDSWilde L, Pan J. Clin Lymphoma Myeloma Leuk. 2019;19:758-762.

Up to 90% of patients with MDS develop anemia, and about half of those have Hb < 10 g/dL.Zeidan AM et al. Blood Rev. 2019;34:1-15. Sekeres MA Taylor J. JAMA. 2022;328:872-880.

Most cases of MDS are idiopathic in nature and patients typically present with non-specific signs and symptoms. Observed cytopenias include anemia, neutropenia, thrombocytopenia, or pancytopenia. Patients with MDS may present with more than one cytopenia. ~40% of patients present with anemia plus either thrombocytopenia or neutropenia.Zeidan AM et al. Blood Rev. 2019;34:1-15. Sekeres MA Taylor J. JAMA. 2022;328:872-880. Weinberg OK, Hasserjian RP. Semin Hematol. 2019;56:15-21. Sperling AS et al. Nat Rev Cancer. 2017;17:5-19. Barzi A, Sekeres MA. Cleve Clin J Med. 2010;77(1):37-44.

Symptomatic anemia leads to MDS diagnosis in nearly 80% of patients. Up to 90% of patients with MDS will require one or more RBC transfusions during the course of their disease. Symptoms associated with anemia include: fatigue, weakness, shortness of breath, chest pains, headache, palpitations, pallor or pale skin, loss of appetite, and cold extremities.

Figure ReferencesSperling AS et al. Nat Rev Cancer. 2017;17:5-19. Barzi A, Sekeres MA. Cleve Clin J Med. 2010;77(1):37-44. Leukemia and Lymphoma Society (LLS). Myelodysplastic Syndromes. Rye Brook, NY; 2022:1-54. Germing U et al. Hemasphere. 2019 Oct 30;3(6):e314.

MDS are more common with advancing ageRotter LK et al. Cancer J. 2023;29:111-121.

≈ 4 in 100,000

people in the United States are diagnosed with MDSSekeres MA Taylor J. JAMA. 2022;328:872-880. Rotter LK et al. Cancer J. 2023;29:111-121.

6-fold increases (25 per 100,000)

in patients aged ≥ 65 years, the incidence of MDS increasesSekeres MA Taylor J. JAMA. 2022;328:872-880.

The survival rate with MDS falls behind those of many solid tumors and hematologic malignanciesZeidan AM et al. Blood Rev. 2019;34:1-15. Surveillance, Epidemiology, and End Results Program. Accessed November 2023. https://seer.cancer.gov/statistics-network/explorer/.

Patients with MDS have poor long-term survival compared with patients who have other cancers, and the overall survival has not improved over the last 2 decades, based on an analysis of SEER data.Zeidan AM et al. Blood Rev. 2019;34:1-15. Surveillance, Epidemiology, and End Results Program. Accessed November 2023. https://seer.cancer.gov/statistics-network/explorer/.

SEER 5-year relative survival rates of patients with cancer in the United States, 2013–2019.Surveillance, Epidemiology, and End Results Program. Accessed November 2023. https://seer.cancer.gov/statistics-network/explorer/.

Horizontal bar chart showing the 5-year relative survival rates of patients with cancer in the US from 2013-2019 with MDS at 37%, AML lower at 32%, Myeloma, CML, and Non-Hodgkin Lymphoma higher at 60%, 71%, and 74% respectively. Under that chart is a separate chart of Solid Tumor 5-year survival rates with Pancreases at 13% up to Prostate at 97%.

AML, acute myeloid leukemia; CML, chronic myeloid leukemia.

Anemia is an important cause of morbidity and mortality in MDSMalcovati L et al. Haematologica. 2011;96:1433-1440. Platzbecker U et al. Leukemia. 2021;35:2182-2198.

The degree of anemia is correlated with clinical outcomes in MDS.Greenberg PL et al. Blood. 2012;120:2454-2465.

Vertical bar chart showing the time for 25% of patients to develop AML in years based on their Hb level. Greater or equal to 10 Hb was 9.5 years with a median survival of 5.5. 8-10 Hb was 5.5 to develop AML and 2.9 median survival. Less than 8 Hb was 2.5 to develop AML and 2 years median survival.

Data are from combined international databases of 7012 patients with primary untreated MDS used to create the IPSS-R.Greenberg PL et al. Blood. 2012;120:2454-2465.

AML, acute myeloid leukemia; Hb, hemoglobin, IPSS-R, Revised International Prognostic Scoring System.

Severe anemia is associated with a higher prognostic risk, a shorter overall survival (OS), and a more rapid evolution to acute myeloid leukemia (AML)Greenberg PL et al. Blood. 2012;120:2454-2465.

Patients with severe anemia have a significantly increased risk of cardiac disease/death compared with those with higher hemoglobin (Hb) levels.Malcovati L et al. Haematologica. 2011;96:1433-1440.

Line chart showing males with a greater than or equal to 9 Hb level and females with a greater than or equal to 8 level have a lower cumulative probability of cardiac disease compared to males with less than 9 and females less than 8 with a gradual increase in probability over time plateauing around 130 months.

Reproduced with permission from Haematologica.Malcovati L et al. Haematologica. 2011;96:1433-1440.

Data based on a prospective, observational cohort analysis of 840 patients with MDS in Pavia, Italy, and 504 patients with MDS in Düsseldorf, Germany. Cox regression analyses were performed, including age, Hb categories, WHO subgroups, cytogenetic risk groups categorized according to the IPSS, number of cytopenias, and cardiac disease as time-dependent covariates.Malcovati L et al. Haematologica. 2011;96:1433-1440.

Hb, hemoglobin; HR, hazard ratio; IPSS, International Prognostic Scoring System; WHO, World Health Organization.

Cardiac diseases, including coronary artery disease, congestive heart failure, myocardial infarction, arrhythmia, and heart valve disease, were the most frequently observed comorbidities of anemiaMalcovati L et al. Haematologica. 2011;96:1433-1440.
Males with Hb levels < 9 g/dL and females with Hb levels < 8 g/dL had significantly more frequent cardiac disease and death compared with those with higher Hb levels (incidence rate ratio [IRR]: 1.70 and 4.22, respectively)Malcovati L et al. Haematologica. 2011;96:1433-1440.

Transfusion dependence negatively impacts the survival of patients with MDSMalcovati L et al. Haematologica. 2006;91:1588-1590. Hiwase DK et al. Am J Hematol. 2017;92:508-514. Braga Lemos M et al. Eur J Haematol. 2021;107:3-23.

MDS-related anemia is often treated with red blood cell (RBC) transfusions. Some patients with MDS may require more frequent transfusions with disease progression.Rozema J et al. Transfusion. 2021;61:2877-2884. Oliva EN et al. Blood Rev. 2021;50:100851. Balducci L. Cancer. 2006;106:2087-2094.

^a Data based on an observational, retrospective, population-based study using the HemoBase registry, including 292 patients diagnosed with MDS between 2005 and 2017 in the Netherlands. Transfusion burden was defined according to the International Working Group (IWG) 2018 guidelines: non-transfusion dependent (NTD; ≥ 2 U/16 wk), LTB (3-7 U/16 wk), and HTB (≥ 8 U/16 wk).Rozema J et al. Transfusion. 2021;61:2877-2884.

The severity of transfusion requirements can be associated with OS in patients with MDS.Malcovati L et al. Haematologica. 2006;91:1588-1590.

Reproduced with permission from Haematologica.Malcovati L et al. Haematologica. 2006;91:1588-1590.

Data based on a retrospective cohort of 426 Italian patients with MDS studied between 1992 and 2004.Malcovati L et al. Haematologica. 2006;91:1588-1590.

PRBC, packed red blood cells.

The effect of transfusion dependence is more noticeable in patients with lower-risk MDS (LR-MDS) and is associated with the severity of transfusion requirements, expressed as the number of PRBC units per month (U/4 wk). An increased transfusion requirement can be an independent predictor of shorter survivalMalcovati L et al. Haematologica. 2006;91:1588-1590.

Transfusion dependence is associated with worse prognosis.Braga Lemos M et al. Eur J Haematol. 2021;107:3-23.

Hazard ratio (HR): 0.44 (95% Cl: 0.34-0.55)

Data based on a multiple Cox regression analysis in a meta-analysis of 4874 patients with MDS from 11 studies that reported OS outcomes for TI vs TD patients at baseline. Interpretation of these data may be limited because most of the studies in this meta-analysis were from observational, retrospective cohorts and abstracts with response rates and follow-up descriptions missing in large part. Confounders may also be present due to some heterogeneity in study parameters, study design, clinical characteristics, definitions, reliability of results, and risk curves.Braga Lemos M et al. Eur J Haematol. 2021;107:3-23.

Patients with MDS who are transfusion independent have a 56% decreased risk of death compared with those who require transfusionsBraga Lemos M et al. Eur J Haematol. 2021;107:3-23.
The HR global effect for OS in the pooled analysis was 0.44 (95% Cl: 0.34-0.55). Most other clinical outcomes, such as AML progression, non-leukemic death, and progression-free survival (PFS), were also associated or had a trend toward worse prognosis in TD patientsBraga Lemos M et al. Eur J Haematol. 2021;107:3-23.

Living with MDS places a heavy burden on patients’ daily livesRia R et al. Clin Interv Aging. 2009;4:413-423. Stauder R et al. Leukemia. 2018;32:1380-1392.

Several studies have shown that the health-related quality of life of patients with MDS is significantly worse compared with the general population.Ria R et al. Clin Interv Aging. 2009;4:413-423. Stauder R et al. Leukemia. 2018;32:1380-1392.

Similarly, caregivers also suffer in a manner similar to patients, reporting a high degree of distress and below average emotional, social, and functional wellbeing.DiNardo KW et al. Blood. 2022;140:8122-8123

Physical problems

MDS causes a substantial and persistent functional decrement in a variety of areas, partially due to fatigueRia R et al. Clin Interv Aging. 2009;4:413-423.
41% of patients with MDS reported moderate or severe mobility issuesStauder R et al. Leukemia. 2018;32:1380-1392.

Data from a study of 1985 newly diagnosed patients in the European Myelodysplastic Syndromes Registry (EUMDS) registry with IPSS low or intermediate-1 MDS compared with the general population in Europe matched on age and sex.Stauder R et al. Leukemia. 2018;32:1380-1392.

Emotional Problems

Patients have often viewed the emotional impact of MDS as being more problematic than the physical consequencesRia R et al. Clin Interv Aging. 2009;4:413-423.
37.9% of patients with MDS reported moderate or severe issues with anxiety/depressionStauder R et al. Leukemia. 2018;32:1380-1392.

Data from a study of 1985 newly diagnosed patients in the EUMDS registry with IPSS low or intermediate-1 MDS compared with the general population in Europe matched on age and sex.Stauder R et al. Leukemia. 2018;32:1380-1392.

Role Functioning

The disease may affect employment, necessitating time off from work or otherwise compromising career opportunitiesSoper J et al. Patient Relat Outcome Meas. 2022;13:31-38.
36.1% of patients with MDS reported moderate or severe problems with usual activities (eg, work, housework, or leisure activities)Stauder R et al. Leukemia. 2018;32:1380-1392.

Social Functioning

Transfusion requirements may disrupt routines and take time and attention away from family and friendsSoper J et al. Patient Relat Outcome Meas. 2022;13:31-38.
34% of patients receiving blood transfusions felt their transfusions were a burden to familySekeres MA et al. Oncologist. 2011;16:904-911.

Data from an internet-based survey of 358 patients with MDS, of whom 234 were receiving transfusions.Sekeres MA et al. Oncologist. 2011;16:904-911.