Myelodysplastic syndromes (MDS) are a heterogeneous group of haematological malignancies characterised by bone marrow dysplasia and peripheral cytopenias.1,2
What is MDS?
In MDS, the bone marrow is, to varying extents, not capable of producing enough platelets and red and white blood cells. This incapacity can result in complications such as anaemia, infections, bruising and a tendency towards bleeding.2
MDS at a Glance
- Affects all ages, but primarily older adults3
- In Europe, new cases of MDS have been estimated at 3–20 per year per 100,000 (higher in older age groups).4
- MDS patients with chronic anemia require frequent blood transfusion5
- Survival time is less than one year in patients with most severe forms of MDS6
- Majority of patients die from complications of blood cell deficiencies7
Typical Symptoms of MDS
Symptoms reflect cytopenia:2
- anaemia (the most common clinical problem)
Intermediate (Int)-2 and High-risk MDS are fatal haematological malignancies.
- For some patients, MDS can progress to acute myeloid leukaemia (AML). Complications due to bone marrow dysfunction (e.g. infections and bleeding) also arise.2
- MDS are fatal malignancies, with a median survival of 1.2 years in Int-2 MDS patients and 0.4 years in high-risk MDS patients, according to the International Prognostic Scoring System (IPSS).6
- VIDAZA® has demonstrated a significant survival benefit in Int-2 and High-risk MDS patients in a large phase III study compared to conventional care regimens.8
Progression to acute myeloid leukaemia (AML) is common (up to 40% of patients with the percentage varying considerably by subtype), as are complications due to bone marrow dysfunction (e.g. infections and bleeding).2
Annual incidence of MDS is approximately 3.2-4.1 cases per 100,000 of the population (all age groups in the EU).9 The incidence of MDS increases with age. In patients over 70, the incidence of MDS rises to more than 30 per 100,000. MDS is more common in men.10,11
MDS are believed to arise and progress due to cumulative genomic alterations that promote abnormal cell growth.7
Cytogenetics and MDS
Cytogenetic abnormalities are found in approximately 50% of patients with newly diagnosed (de novo) MDS. The most common abnormality is interstitial deletion of the long arm of chromosome 5 (del 5q). Other frequently encountered abnormalities include deletion or monosomy of chromosome 7, trisomy or multiple abnormalities. Cytogenetics can influence the prognosis of MDS, as seen in the World Health Organisation (WHO) classification system of MDS.12
National Comprehensive Cancer Network (NCCN) Guidelines for Initial Evaluation of Patients with Suspected Myelodysplastic Syndromes:13
- Take a comprehensive history and physical examination
- Document transfusion history
- Complete blood cell count with differential
- Reticulocyte count
- Examination of peripheral smear
- Bone marrow aspiration and biopsy with iron stain
- Cytogenetic studies
- Obtain serum erythropoietin level before red blood cell transfusion
- Red blood cell folate and serum vitamin B12 levels
- Iron studies (ferritin, serum iron, and total iron-binding capacity)
MDS Classification Systems
FAB Classification System
The FAB classification system was proposed in 1982, based on the percentage of blast cells in the peripheral blood and bone marrow.14
WHO Classification System
More recently the WHO proposed a modified classification system, which refines the definition of some of the subtypes of MDS.
Adapted from Malcovati L et al.1
The International Prognostic Scoring System (IPSS)
The IPSS was introduced in 1997 as a means to predict clinical outcomes and improve prognostic power1
The IPSS is based on 3 prognostic factors:
- Blast percentage in the bone marrow (< 5%, 5-10%, 11-20%, 21-30%)
- Number and degree of cytopenias
Based on these prognostic factors, the IPSS stratifies patients into four distinct risk groups: Low, Intermediate (Int)-1, Int-2 and High, with regard to leukaemia transformation and mortality6
Karotype: Good=normal. 5q-, 20q, -Y ; Poor=complex (≥ 3 karyotypic abnormalities), chromosome 7 anomalies; Intermediate=other anomalies. Cytopenias: Platelets < 100×109 A, haemoglobin < 10 g/dl, neutrophils < 1.5×109 A1,15
Int-2 & High-risk MDS are fatal haematological malignancies: Median survival is 1.2 years in Int-2 risk patients and 0.4 for High-risk MDS patients6
Current Treatment Options for MDS
The mainstay of MDS treatment is predominantly supportive care, with no proven effect on improving survival or impact on the underlying disease.16
Evaluating responses to MDS treatment
An International Working Group (IWG) developed standard response criteria for MDS in 2000. The IWG Response Criteria are listed below:17
Complete remission (CR)
- Blood (absolute values must last at least 2 months)
- Haemoglobin: ≥ 11g/dL (patient untransfused and not on erythropoietin)
- Platelets: ≥ 100 000/mm3 (not on a thrombopoetic agent)
- Neutrophils: ≥ 1500/mm3 (not on a myeloid growth factor)
- Bone marrow evaluation
- < 5% myeloblasts with normal maturation of all cell lines; no evidence for dysplasia
Partial remission (PR)
Same as complete response, except bone marrow evaluation: Blasts: If ≥ 5% at baseline, decrease ≥ 50%, or less-advanced FAB class than pretreatment
- Haematological improvement (sustained ≥ 8 weeks; HI)
- Erythroid response (for patients with Hb < 11g/dL before treatment)
- Major: Hb > 2 g/dL increase or RBC transfusion independence
- Minor: 1 or 2 g/dL Hb increase or 50% reduction in RBC transfusion needs
- Platelets (for patients with platelets < 100 000/mm3 before treatment)
- Major: ≥ 30 000/mm3 increase or platelet transfusion independence
- Minor: ≥ 50% increase or between 10 000/mm3 and 30 000/mm3 increase
- Neutrophils (for patients with absolute neutrophil count (ANC) < 1500/mm3 before treatment)
- Major: ANC ≥ 100% increase or more than a 500/mm3 increase
- Minor: ANC ≥ 100% increase but less than a 500/mm3 increase
- Malcovati L et al. J Clin Oncol 2005. 23: 7594-7603.
- Kurzrock R. Semin Hematol 2002. 39(Suppl 2): 18-25.
- Aul C et al. Leuk Lymphoma. 1995.16: 247-262.
- Ross SD et al. Oncologist. 2007. 12:1264-1273.
- Kouides PA, Bennett JM. Understanding myelodysplastic syndromes: a patient handbook. 3rd edition. Myelodysplastic Syndromes Foundation. 2004.
- Greenberg P, et al. Blood. 1997. 89: 2079-2088.
- List AF et al. Hematology Am Soc Hematol Educ Program 2004. 2004: 297-317.
- Fenaux P et al. Lancet Oncology 2009. 10:223-232.
- Rollison DE et al. Blood 2008. 112: 45-52.
- Bowen D. Br J Haematol 2003. 120: 187-200.
- Hamblin TJ. Epidemiology of MDS. In: Bennett JM (ed).MDS: Pathobiology and Clinical Management. New York:Marcel Dekker Inc. 2002.
- Giagounidis A. Haematologica Reports 2006. 2: 5-10.
- NCCN Guidelines on Myelodysplastic Syndromes V.2.2011.
- Bennett JM et al. Br J Haematol 1982. 51: 189-199.
- Greenberg P et al. Blood 1998. 91: 1100.
- List AF and Doll DC. Myelodysplastic syndromes. In: Wintrobeʼs clinical hematology, 2004.
- Cheson B et al. Blood 2000. 96: 3671-3674.
a. MDS-specific Indication
VIDAZA® is indicated for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with:
- intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS),
- chronic myelomonocytic leukaemia (CMML) with 10-29% marrow blasts without myeloproliferative disorder
b. AML-specific Indication:
Treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20-30% blasts and multi-lineage dysplasia, according to the WHO classification. WHO classifies RAEB-T patients with blasts ≥20% to <30% as AML patients.
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The information on this website is based on the European Summary of Product Characteristics (SmPC). Please refer to your country-specific website, or contact a Celgene representative in your country for the latest information specific to your country.