Myelodysplastic Syndromes Guidelines 

Updated: Dec 13, 2016
  • Author: Emmanuel C Besa, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Myelodysplastic Syndrome (MDS) Classification

In 2016, the World Health Organization (WHO) released a revision to its 2008 classification scheme for myelodysplastic syndrome (MDS). [1] The National Comprehensive Cancer Network (NCCN) has included the revised WHO classification system in its 2016 updated guidelines. [2]

The two systems are compared in the table below..

Table. 2008 and 2016 World Health Organization (WHO) classifications of myelodysplastic syndromes (Open Table in a new window)

2008 WHO Classification [1] 2016 WHO Classification [13]
Refractory cytopenia with unilineage dysplasia (RCUD) encompassing refractory anemia (RA), refractory neutropenia (RN), and refractory thrombocytopenia (RT) MDS with single lineage dysplasia (MDS-SLD)
Refractory cytopenia with multilineage dysplasia (RCMD) MDS with multilineage dysplasia (MDS-MLD)
Refractory anemia with ringed sideroblasts (RARS) MDS with ring sideroblasts (MDS-RS)
       MDS-RS with single lineage dysplasia (MDS-RS-SLD)
       MDS-RS with multilineage dysplasia (MDS-RS-MLD)                                                                                                                                               
Myelodysplastic syndrome associated with isolated del(5q)      MDS with isolated del(5q)
  MDS with excess blasts (MDS-EB)
Refractory anemia with excess blasts–1 (RAEB-1)     MDS with excess blasts-1 (MDS-EB-1)
Refractory anemia with excess blasts–2 (RAEB-2)     MDS with excess blasts-2 (MDS-EB-2)
Myelodysplastic syndrome, unclassified (MDS-U) MDS, unclassifiable (MDS-U)
       with 1% blood blasts
       with single lineage dysplasia and pancytopenia
       based on defining cytogenetic abnormality
Refractory cytopenia of childhood Refractory cytopenia of childhood

 

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Diagnosis

The 2016 NCCN utilizes the WHO classification system for diagnosis and distinguishes subtypes on the basis of blood and bone marrow findings. [2, 13]

MDS with single lineage dysplasia (MDS-SLD) criteria are as follows:

  • Blood: single cytopenia or bicytopenia
  • Bone marrow: dysplasia in ≥ 10% of one cell line, <5% blasts

MDS with ring sideroblasts (MDS-RS) criteria are as follows:

  • Blood: anemia, no blasts
  • Bone marrow: ≥15% of erythroid precursors with ring sideroblasts, or ≥5% blasts ring sideroblasts if SF3B1 mutation is present

MDS with multilineage dysplasia (MDS-MLD) criteria are as follows:

  • Blood: cytopenia(s), <1 × 10 9/L monocytes
  • Bone marrow: dysplasia in ≥10% of cells in two or more hematopoietic lineages, ±15% ring sideroblasts, <5% blasts

MDS with excess blasts-1 (MDS-EB-1) criteria are as follows:

  • Blood: cytopenia(s) ≤2-4% blasts, <1 × 10 9/L monocytes
  • Bone marrow: unilineage or multilineage dysplasia, no Auer rods, 5-9% blasts

MDS with excess blasts-2 (MDS-EB-2) criteria are as follows:

  • Blood: cytopenia(s), 5-19% blasts, <1 × 10 9/L monocytes
  • Bone marrow: unilineage or multilineage dysplasia, ±Auer rods, 10-19% blasts

Myelodysplastic syndrome–unclassified (MDS-U) criteria are as follows:

  • Blood: cytopenias, ±1% blasts on at least 2 occasions 
  • Bone marrow: unilineage dysplasia or no dysplasia but characteristic MDS cytogenetics, <5% blasts

Myelodysplastic syndrome associated with isolated del(5q) criteria are as follows:

  • Blood: anemia, platelet levels normal or increased
  • Bone marrow: unilineage erythroid dysplasia, isolated del(5q), <5% blasts

 

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Prognostic Scoring Systems

The following prognostic scoring systems are most commonly used:

  • International Prognostic Scoring System (IPSS and IPSS-R)
  • WHO Prognostic Scoring System (WPSS)
  • Lower-Risk Prognostic Scoring System (LR-PSS)

National Comprehensive Cancer Network (NCCN) guidelines prefer the IPSS-R over the IPSS or WPSS, and find its predictive power to be comparable to LR-PSS. [2] The European Society of Medical Oncology (ESMO) guidelines also recommend IPSS-R while noting that gene mutation profiling (ie, TP53, EZH2, ETV6, RUNX1, ASXL1) may also improve risk stratification but data are still lacking to recommend its use in routine practice. [3] In contrast, European LeukemiaNet (ELN) recommends that all patients be risk stratified using IPSS. [4]

International Prognostic Scoring System

The IPSS has been the most widely used prognostic scoring system for MDS. First published in 1997, it was intended for use with the FAB classification system. The following three factors are rated [5] :

  • The percentage of blasts in the bone marrow (scored on a scale from zero to 2)
  • Karyotype (scored from zero to 1)
  • Cytopenias (scored as zero or 0.5)

Each factor is given a score and totaled and the patient’s risk is classified according to the following:

  • 0 = Low risk
  • 0.5-1 = Intermediate risk - 1
  • 1.5-2 = Intermediate risk - 2
  • ≥2 = High risk

In 2012, a revised IPSS (IPSS-R) was released with five risk groups (very low, low, intermediate, high and very high). It refined the original model by incorporating more detailed cytogenetic prognostic categorization and cut-offs for hemoglobin levels, platelet counts and neutrophil count. The prognostic score is now weighted according to the severity of cytopenias in addition to the bone marrow blast percentage. [6]

WHO Prognostic Scoring System (WPSS)

The WHO Prognostic Scoring System (WPSS) was developed in 2005 based on the 2001 WHO classifications and refined most recently in 2011. In contrast to the IPSS and IPSS-R, which are applied only at the time of diagnosis, the WPSS is dynamic, and patients can be reassigned categories as their disease progresses. The WHO score is calculated on the basis of the following three factors [7] : [8]

  • WHO disorder classification (0-3)
  • Karyotype (0-2)
  • Presence or absence of severe anemia (0-1)

Based on the total score, risk classification is as follows:

  • 0 = Very Low
  • 1 = Low
  • 2 = Intermediate
  • 3-4 = High
  • ≥5 = Very High

Lower-Risk Prognostic Scoring System (LR-PSS)

In 2008, researchers at MD Anderson Cancer Center developed the Lower-Risk Prognostic Scoring System (LR-PSS) to identify patients with very low or low risk with a poorer prognosis. The model is a refinement of IPSS and included the following factors that were independent predictors of survival outcomes:

  • Unfavorable cytogenetics
  • ≥60 years old
  • Decreased hemoglobin level
  • Decreased platelet count
  • Higher percentage of bone marrow blasts

Each factor was given a weighted score and based on the total, patients were assigned to one of the following risk categories:

  • 0-2 = Category 1
  • 3-4 = Category 2
  • ≥5 = Category 3

The categories can be viewed as risk subgroups for either IPSS low-risk or intermediate-1 risk patients.

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Supportive Care for MDS

The National Comprehensive Cancer Network guidelines recommend supportive care as the standard of care for patients with lower-risk MDS. Supportive care includes the following [2] :

  • Clinical monitoring, psychosocial support and quality of life assessment
  • Red blood cell (RBC) transfusions for symptomatic anemia
  • Platelet transfusions for thrombocytopenic bleeding; aminocaprioic acid may be considered for profound thrombocytopenia
  • Cytomegalovirus (CMV)-negative or leuko-reduced blood products for CMV-negative transplant candidates
  • No routine antibiotic prophylaxis except in patients with recurrent infections
  • Management of iron overload in patients who have received >20 to 30 RBC transfusions with deferoxamine subcutaneously or deferasirox orally, except in patients with low creatinine clearance (<40 mL/min)
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Treatment of Lower-Risk MDS

In lower-risk MDS patients, all three guidelines recommend the following for treatment of symptomatic anemia [2, 4, 3]

  • Patients without del(5q): Erythropoiesis-stimulating agents (ESAs); recombinant erythropoietin (EPO) or darbepoetin (DAR); granulocyte colony-stimulating factor (G-CSF) may be added
  • Patients with del(5q):  Lenalidomide

For patients with neutropenia and thrombocytopenia, NCCN guidelines recommend azacitidine/decitabine or immunosuppressive therapy in selected cases. [2]  

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Treatment of Higher-Risk MDS

NCCN guidelines recommendations for treatment of higher-risk MDS include the following [2] :

  • Allogeneic hematopoietic stem cell transplant (HSCT)
  • For non-transplant candidates or for candidates with no response or relapse after transplantation, azacitidine (preferred; category 1) or decitabine

The ESMO and ELN guidelines offer similar recommendations.

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